Slide
1
of
37
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment
FIFRA
Scientific
Advisory
Panel
August
23­
26,
2005
FIFRA
Scientific
Advisory
Panel
August
23­
26,
2005

Session
1
°
Public
Comments
°
Hazard
Assessment

Session
2
°
Drinking
Water
Exposure
Assessment

Session
3
°
Food
&
Residential
Exposure
Assessment

Session
4
°
Model
Results
Comparison,
Cumulative
(

Multipathway
Analysis,
&
Risk
Characterization
Sessions
Roadmap
Slide
2
of
37
Slide
3
of
37
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Model
Results
Comparison,

Cumulative
(
Multi­
pathway)
Analysis,

&
Risk
Characterization
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Model
Results
Comparison,

Cumulative
(
Multi­
pathway)
Analysis,

&
Risk
Characterization
Health
Effects
Division
Office
of
Pesticide
Programs
Health
Effects
Division
Office
of
Pesticide
Programs
Slide
4
of
37
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Comparison
of
Model
Results
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Comparison
of
Model
Results
Alan
Dixon
Health
Effects
Division
Office
of
Pesticide
Programs
Alan
Dixon
Health
Effects
Division
Office
of
Pesticide
Programs
Slide
5
of
37
Model
Result
Comparison
Overview

Comparison
of
MOEs
calculated
from
Calendex
 
,
CARES
 
,
&
LifeLine
 
exposures:

°
Food
Only
(
National)

°
Water
Only,
two
examples

Surface
water
from
North
Carolina

Ground
water
from
Florida
Central
Ridge
private
well
water
°
Food
+
Water

Ground
water
from
Florida
central
ridge
well
water

Summary

Future
Work
Slide
6
of
37
Model
Result
Comparison
Overview

EPA
has
not
yet
determined:

°
Target
MOEs

Uncertainty
and
safety
factors
not
yet
determined
°
Percentile
of
regulation
for
exposure

Exposure
models
sum
exposures
over
24
hours
°
Risk
Characterization
presentation
will
follow
and
will
discuss
the
impact
of
summing
exposures
over
24
hours
Slide
7
of
37
Model
Result
Comparison
Food
Only

Compare
dietary
exposure
at
upper
percentiles
95,
99,
and
99.9
percentiles

Models
produce
similar
exposures
and
MOE's
°
Use
similar
input
data
and
computational
algorithms

There
are
minor
differences
in
exposures
and
MOE's
between
models
°
Due
to
variations
on
assumptions,
selection
of
data
records,
and
how
the
data
is
sampled.


This
was
covered
in
SAP
April
2004
Model
Results
Comparison
Food
Only
*
Exposures
are
in
mg/
kg/
day
in
oxamyl
equivalents
101
0.001389
628
0.000223
3812
0.000037
LifeLine
 
110
0.001278
605
0.000231
3913
0.000036
CARES
 
109
0.001279
633
0.000221
4118
0.000034
DEEM/
Calendex
 
20
to
49
yr
olds
40
0.003474
208
0.000672
1151
0.000122
LifeLine
 
41
0.003449
204
0.000688
1199
0.000117
CARES
 
42
0.003368
201
0.000696
1094
0.000128
DEEM/
Calendex
 
3
to
5
yr
olds
33
0.004207
210
0.000666
1076
0.000130
LifeLine
 
37
0.003771
194
0.000720
1053
0.000133
CARES
 
37
0.003773
188
0.000745
979
0.000143
DEEM/
Calendex
 
1
to
2
yr
olds
118
0.001189
779
0.000180
3128
0.000045
LifeLine
 
111
0.001257
823
0.000170
3892
0.000036
CARES
 
109
0.001288
741
0.000189
3415
0.000041
DEEM/
Calendex
 
Infants
<
1
years
old
MOE
Exp*

MOE
Exp*

MOE
Exp*

Model
99.9th
Percentile
99th
Percentile
95th
Percentile
Slide
8
of
37
Slide
9
of
37
Model
Result
Comparison
Water
Only

Two
examples
provided
here:

°
Surface
water
from
North
Carolina
°
Ground
water
from
Central
Ridge
Florida

Both
examples
are
high
end
estimates
for
drinking
water
sources

For
most
of
the
country,
NMC
residues
in
drinking
water
are
not
expected
to
contribute
substantially
to
cumulative
exposure
Southeast
Florida
Mid­
south
North
Central
/
Northeast
Northern
Great
Plains
Lower
Midwest
Southwest
Northwest
Cumulative
Regions
NC
Surface
Water
FL
Central
Ridge
Well
Water
Slide
10
of
37
Model
Results:
Surface
Water
Only
North
Carolina
Coastal
Plain
*
Exposures
are
in
mg/
kg/
day
in
oxamyl
equivalents
2591
0.00005
11920
0.00001
68966
2.03E­
06
LifeLine
 
1949
0.000072
7269
0.000019
36978
3.79E­
06
CARES
 
2059
0.000068
7778
0.000018
39437
3.55E­
06
DEEM/
Calendex
 
20
to
49
yr
olds
1349
0.00010
5753
0.00002
31042
4.51E­
06
LifeLine
 
1254
0.000112
4970
0.000028
24544
5.70E­
06
CARES
 
1359
0.000103
5185
0.000027
26415
5.30E­
06
DEEM/
Calendex
 
3
to
5
yr
olds
1182
0.00012
5226
0.00003
28986
4.83E­
06
LifeLine
 
1214
0.000115
4977
0.000028
26341
5.32E­
06
CARES
 
1239
0.000113
4828
0.000029
25926
5.40E­
06
DEEM/
Calendex
 
1
to
2
yr
olds
681
0.00021
2495
0.00006
14698
9.53E­
06
LifeLine
 
503
0.000278
2186
0.000064
13220
1.06E­
05
CARES
 
522
0.000268
2090
0.000067
11667
1.20E­
05
DEEM/
Calendex
 
Infants
<
1
years
old
MOE
Exp*

MOE
Exp*

MOE
Exp*

Model
99.9th
Percentile
99th
Percentile
95th
Percentile
Slide
11
of
37
Limited
Extent
 
Florida
Central
Ridge
Well
Water
Overlaying
citrus
(
orange
color)
with
highly
permeable
soils
(
blue)
shows
the
potential
extent
of
the
high
GW
exposure
areas
(
dark
color)
for
shallow
well
water
Slide
12
of
37
Model
Results:
Ground
Water
Only
Florida
Central
Ridge
Private
Well
Water
*
Exposures
are
in
mg/
kg/
day
in
oxamyl
equivalents
26
0.005359
47
0.002958
92
0.001528
LifeLine
21
0.006697
42
0.003308
68
0.002069
CARES
19
0.007251
39
0.003587
70
0.002013
DEEM/
Calendex
20
to
49
yr
olds
17
0.008011
25
0.005511
46
0.003026
LifeLine
15
0.009033
27
0.005274
46
0.003050
CARES
15
0.009502
26
0.005427
45
0.003105
DEEM/
Calendex
3
to
5
yr
olds
14
0.009841
22
0.006503
38
0.003676
LifeLine
 
12
0.012000
22
0.006483
38
0.003650
CARES
 
13
0.011158
22
0.006246
39
0.003546
DEEM/
Calendex
 
1
to
2
yr
olds
11
0.012552
15
0.009427
21
0.006549
LifeLine
 
7
0.020710
11
0.013180
18
0.007861
CARES
 
7
0.021160
10
0.013532
17
0.008145
DEEM/
Calendex
 
Infants
<
1
years
old
MOE
Exp*

MOE
Exp*

MOE
Exp*

Model
99.9th
Percentile
99th
Percentile
95th
Percentile
Slide
13
of
37
Model
Results:

Food+
Florida
Central
Ridge
Well
Water
*
Exposures
are
in
mg/
kg/
day
in
oxamyl
equivalents
26
0.005438
46
0.003015
90
0.001558
LifeLine
 
21
0.006757
42
0.003338
67
0.002091
CARES
 
20
0.006958
39
0.003551
68
0.002048
DEEM/
Calendex
 
20
to
49
yr
olds
17
0.008340
25
0.005621
45
0.003112
LifeLine
 
15
0.009033
26
0.005403
45
0.003133
CARES
 
13
0.010393
25
0.005686
44
0.003208
DEEM/
Calendex
 
3
to
5
yr
olds
14
0.010329
21
0.006654
37
0.003765
LifeLine
 
15
0.009431
26
0.005462
44
0.003177
CARES
 
13
0.010839
23
0.006154
40
0.003497
DEEM/
Calendex
 
1
to
2
yr
olds
11
0.012630
15
0.009441
21
0.006571
LifeLine
 
7
0.020710
11
0.013180
18
0.007873
CARES
 
6
0.022153
10
0.013529
17
0.008163
DEEM/
Calendex
 
Infants
<
1
years
old
MOE
Exp*

MOE
Exp*

MOE
Exp*

Model
99.9th
Percentile
99th
Percentile
95th
Percentile
Slide
14
of
37
Slide
15
of
37
Model
Results
Comparison
Conclusions

Similarity
of
predicted
exposures
between
models
is
encouraging

DEEM/
Calendex
 
,
CARES
 
and
LifeLine
 
produce
similar
estimated
dietary
exposures
at
99.9,
99
and
95
percentiles

The
major
food
contributors
at
the
upper
percentiles
are
the
same
for
these
three
models

Modeled
water
only
and
combined
food
and
water
also
produce
similar
predicted
exposures
and
risks
Slide
16
of
37
Model
Results
Comparison
Future
Work

Food
and
Drinking
Water
°
Continue
analyses
on
model
stability,
sensitivity
analyses,
&

comparison
of
results

Residential
°
Continue
modeling
work
on
selected
residential
scenarios
with
CARES
 
&
LifeLine
 

Work
with
ORD
SHEDS
model
Slide
17
of
37
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Multi­
Pathway
Risk
Assessment
Session
4
Preliminary
N­
Methyl
Carbamate
Cumulative
Risk
Assessment:

Multi­
Pathway
Risk
Assessment
David
Hrdy
Health
Effects
Division
Office
of
Pesticide
Programs
David
Hrdy
Health
Effects
Division
Office
of
Pesticide
Programs
Slide
18
of
37
Outline

What
we've
done
since
the
Feb
2005
SAP

Chemicals

Routes
+
Pathways

Description
of
risk
profile
graphs
Slide
19
of
37
Since
the
Feb.
2005
SAP
on
the
Case
study

MOEs
have
been
calculated

Final
RPF
and
PoDs
developed

Estimated
ground
water
concentrations
added

Residential:

°
Refined
our
scenarios
and
inputs
°
Described
more
fully
our
rationale
for
separating
or
combining
scenarios
and
selecting
input
parameters
°
Made
greater
use
of
statistical
and
distributional
analyses
Slide
20
of
37
N­
Methyl
Cumulative
Risk
Assessment

Ten
chemicals
with
common
mechanism
of
toxicity
°
Aldicarb,
propoxur,
thiodicarb,

methomyl,
oxamyl,
methiocarb,

carbofuran,
carbaryl,
pirimicarb,
and
formetanate
HCl

Normalized
into
oxamyl
equivalents
Slide
21
of
37
N­
Methyl
Cumulative
Risk
Assessment

Multiple
pathways
of
exposure
°
e.
g.,
food,
drinking
water,
indoor
surfaces,
air

Multiple
routes
of
exposure
°
Oral,
dermal,
inhalation
Key
Concepts
in
Cumulative
Assessment

Important
to
"
integrate"
or
combine
these
route
specific
estimated
exposures
in
an
internally
consistent
manner
to
develop
a
total
risk
picture
°
Integrated
(
or
Combined)

Exposure
=
"
Total
MOE"

°
"
Appropriate
Matching
and
Combining"
dermal
dermal
Exposure
PoD
MOE
=

1
1
MOEdermal
1
1
+
+
MOEinhalation
MOEoral
MOEtotal
=
oral
oral
Exposure
PoD
MOE
=
inhalation
inhalation
Exposure
PoD
MOE
=
Slide
22
of
37
Slide
23
of
37
Slide
24
of
37
Populations
Groups
Assessed

Separate
assessments
were
based
on
survey
information
on
the
following
age
groups:

°
Children
1­
2
years
old
°
Children
3­
5
years
old
°
Adults
20­
49
°
Adults
50+


For
the
Revised
N­
Methyl
Carbamate
Cumulative
Risk
Assessment,
the
remaining
age
groups
will
be
included
Slide
25
of
37
Example
Outputs
"
MOE
Profile
Graphs"


The
following
graphs
represent
the
Florida
Central
Ridge
area
°
Additional
graphs
can
be
found
in
Appendix
II.
F.
1­
2

Each
line
in
the
graph
represents
a
separate
pathway
of
risk
in
MOEs
°
Expressed
in
terms
of
MOE
for
index
chemical
(
oxamyl)

°
Example
subpopulation
presented
here
is
Children
1­
2
years
old
Slide
26
of
37
Cumulating
MOEs

This
series
of
daily
MOE
distributions
is
arrayed
as
distribution
across
time
(
one
year)


The
MOEs
developed
such
that
the
exposures
from
NMCs
in
foods,
drinking
water
and
from
residential
uses
are
all
calculated
simultaneously
for
each
individual.


Preliminary
risk
assessment
focuses
on
regional
locations
which
are
believed
to
represent
higher
end
exposure
potential
due
to
usage,
pest
pressures,
and
other
environmental
factors.

°
NMC
exposures
in
drinking
water
from
the
remaining
parts
of
the
country
are
expected
to
be
substantially
lower
than
from
these
sites
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
16
28
40
52
64
76
88
100
112
124
136
148
160
172
184
196
208
220
232
244
256
268
280
292
304
316
328
340
352
364
Julian
Days
MOEs
at
the
99.9th
Percentile
Inhalation
MOE
Slide
27
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
15
26
37
48
59
70
81
92
103
114
125
136
147
158
169
180
191
202
213
224
235
246
257
268
279
290
301
312
323
334
345
356
Julian
Days
MOEs
at
the
99.9th
Percentile
Inhalation
MOE
Dermal
MOE
Slide
28
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
13
22
31
40
49
58
67
76
85
94
103
112
121
130
139
148
157
166
175
184
193
202
211
220
229
238
247
256
265
274
283
292
301
310
319
328
337
346
355
364
Julian
Days
MOEs
at
the
99.9th
Percentile
Drinking
Water
MOE
Inhalation
MOE
Dermal
MOE
Slide
29
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
15
26
37
48
59
70
81
92
103
114
125
136
147
158
169
180
191
202
213
224
235
246
257
268
279
290
301
312
323
334
345
356
Julian
Days
MOEs
at
the
99.9th
Percentile
Food
MOE
Drinking
Water
MOE
Inhalation
MOE
Dermal
MOE
Slide
30
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
15
26
37
48
59
70
81
92
103
114
125
136
147
158
169
180
191
202
213
224
235
246
257
268
279
290
301
312
323
334
345
356
Julian
Days
MOEs
at
the
99.9th
Percentile
Food
MOE
Drinking
Water
MOE
Inhalation
MOE
Dermal
MOE
Oral
(
non­
dietary)
MOE
Slide
31
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
4
15
26
37
48
59
70
81
92
103
114
125
136
147
158
169
180
191
202
213
224
235
246
257
268
279
290
301
312
323
334
345
356
Julian
Days
MOEs
at
the
99.9th
Percentile
Food
MOE
Drinking
Water
MOE
Total
MOE
Inhalation
MOE
Dermal
MOE
Oral
(
non­
dietary)
MOE
Slide
32
of
37
Cumulative
MOEs
for
Children
1­
2
in
FL
Central
Ridge
using
Ground
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
1000000
1
15
29
43
57
71
85
99
113
127
141
155
169
183
197
211
225
239
253
267
281
295
309
323
337
351
Julian
Days
MOEs
at
the
99th
Percentile
Total
MOE
Inhalation
MOE
Dermal
MOE
Oral
(
non­
dietary)
MOE
Food
MOE
Drinking
Water
MOE
Slide
33
of
37
Cumulative
MOEs
for
Children
1­
2
in
NC
Coastal
Plain
using
Surface
Water
in
a
Daily
Analysis
1
10
100
1000
10000
100000
1000000
10000000
100000000
1000000000
4
16
28
40
52
64
76
88
100
112
124
136
148
160
172
184
196
208
220
232
244
256
268
280
292
304
316
328
340
352
364
Julian
Days
MOEs
at
the
99.9th
Percentile
Food
MOE
Drinking
Water
MOE
Total
MOE
Inhalation
MOE
Dermal
MOE
Oral
(
non­
dietary)
MOE
Slide
34
of
37
Slide
35
of
37
Conclusions

Relative
Risk
by
Pathway
°
Calendex
was
used
to
estimate
risks
through
each
of
the
three
pathways
Risksoral>
Risksdermal>
Risksinhalation
Slide
36
of
37
Conclusions

OPP
now
has
several
models
to
estimate
cumulative
risk
and
is
using
them
per
the
SAP's
recommendations

Preliminary
calculations
by
OPP
suggested
that
oral
exposure
is
the
primary
contributor
to
total
risk
°
This
oral
exposure
is
contributed
from
all
three
pathways,
hand
to
mouth,
drinking
water
and
food
°
Hand
to
mouth
contributes
to
risk
via
the
pet
collars
and
crack
and
crevice
exposure
Slide
37
of
37
Conclusions

NMC
in
water
can
significantly
contribute
to
the
overall
risk
in
defined
areas
of
the
U.
S.

°
In
most
areas
of
the
U.
S.,
NMC
residues
in
drinking
water
do
not
contribute
substantially
to
cumulative
exposure

Sensitivity
analyses
will
continue

OPP
will
continue
to
refine
these
inputs
where
appropriate
