Document ID: EPA-HQ-OPP-2004-0005-0014
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-03-08T05:00Z

Appendix
H,
Page
1
of
6
Appendix
H:
Dermal
Toxicity
Estimation
In
the
March
2000
SAP
for
the
implementation
of
probabilistic
risk
assessments,
one
question
posed
to
the
panel
concerned
dermal
toxicity
estimation.
The
SAP
was
concerned
about
the
potential
approach
of
applying
the
ratio
of
oral­
to­
dermal
toxicity
from
mammals
to
birds.
A
limited
set
of
data
exists
for
evaluating
the
relationship
between
dermal
toxicity
and
oral
toxicity
in
birds
(
Table
H­
1).
Definitive
oral
and
dermal
LD
50'
s
are
available
for
42
individual
studies.
These
studies
were
conducted
across
a
variety
of
species
and
several
classes
of
chemicals.

Regression
analysis
was
used
to
predict
the
dermal
LD
50
based
on
the
oral
LD
50.
In
addition,
pesticide
chemical
properties
were
included
into
the
regression
model
in
an
attempt
to
improve
the
model
fit,
similar
to
the
approach
taken
by
Mineau
(
2002).
Prior
to
regression
analysis,
the
dermal
LD
50
data
and
the
oral
LD
50
data
to
were
transformed
to
the
log­
base10
scale
to
better
meet
assumptions
of
normality
and
homogeneous
variance.

In
the
log
transformed
scale,
the
correlation
coefficient
between
the
dermal
and
oral
LD
50
values
was
0.55
(
Figure
H­
1).
The
correlation
coefficients
between
dermal
LD
50
and
the
evaluated
chemical
properties
were
much
lower:
­
0.11,
­
0.03,
and
­
0.03
for
molecular
weight
(
MW),
density,
and
molecular
volume
(
MV),
respectively.

Figure
H­
1.
Plot
of
dermal
LD
50
values
vs.
oral
LD
50
values
in
log­
base
10
scale.
The
correlation
coefficient
was
0.55.
Appendix
H,
Page
2
of
6
log
.
.
*
log
DermalLD
OralLD
50
50
084
0
62
=
+

standard
errors:
(
0.14)
(
0.15)
A
summary
of
the
evaluated
regression
models
is
provided
in
Table
H­
2.
This
analysis
indicates
that
the
addition
of
these
chemical
properties
into
the
regression
model
do
not
significantly
improve
its
predictive
ability.
The
adjusted
R­
square
(
a
modified
R­
square
with
a
correction
for
the
number
of
parameters
included
in
the
model)
ranged
between
0.2575
and
0.2857,
indicating
little
difference
in
the
predictive
ability
among
the
fitted
models.
The
best
fitting
model
to
predict
dermal
LD
50
was
one
based
solely
on
oral
LD
50:

The
p­
value
for
the
slope
was
0.0002
and
the
R­
square
was
0.30.
The
chemical
properties
that
were
included
did
not
provide
significant
improvement
in
the
predictive
ability
of
the
model.
Appendix
H,
Page
3
of
6
Table
H­
1:
Raw
Data
from
Regression
Analysis
of
Avian
Dermal
LD50
and
Oral
LD50
Compound
Class
Species
Oral
LD50
(
mg/
kg)
Dermal
LD50
(
mg/
kg)
Footnotea
Molecular
Weight
Density
Molar
Volume
(
mol/
cm3)

Aldicarb
Carbamate
Mallard
3.4
60.0
1
190.26
1.195
159.21
Carbofuran
Carbamate
House
sparrow
1.3
100.0
2
221.26
1.18
187.51
Carbofuran
Carbamate
Quelea
0.42
100.0
2
221.26
1.18
187.51
Coumaphos
OP
House
sparrow
10
75.0
2
362.80
1.47
246.80
Coumaphos
OP
Quelea
3.2
7.5
2
362.80
1.47
246.80
Demeton
OP
Mallard
7.19
24
1
258.34
1.18
218.93
Demeton
OP
House
sparrow
5.6
13.0
2
258.34
1.18
218.93
Demeton
OP
Quelea
1.3
1.8
2
258.34
1.18
218.93
Dicrotophos
OP
Mallard
4.24
14.2
1
237.19
1.216
195.06
Dicrotophos
OP
House
sparrow
4.2
1.8
2
237.19
1.216
195.06
Dicrotophos
OP
Quelea
1.3
1.3
2
237.19
1.216
195.06
Disulfoton
OP
Mallard
6.54
192.0
1
274.39
1.144
239.85
Disulfoton
OP
Starling
133
13.3
3
274.39
1.144
239.85
Disulfoton
OP
Red­
winged
Blackbird
3.2
1.00
3,
4
274.39
1.144
239.85
Endrin
OChl
Mallard
5.64
>
140.0b
1
380.93
1.7
224.08
EPN
OP
Mallard
7.09
400.0
1
323.31
1.3
248.70
Ethoprop
OP
Mallard
12.6
10.6
1
242.3
1.094
221.48
Fenamiphos
OP
Mallard
1.68
23.8
1
303.36
1.15
263.79
Fenitrothion
OP
Mallard
1190
504.0
1
277.23
1.33
208.44
Fensulfothion
OP
Mallard
0.749
2.86
1
308.35
1.202
256.53
Fensulfothion
OP
House
sparrow
0.32
1.00
2
308.35
1.202
256.53
Compound
Class
Species
Oral
LD50
(
mg/
kg)
Dermal
LD50
(
mg/
kg)
Footnotea
Molecular
Weight
Density
Molar
Volume
(
mol/
cm3)

Appendix
H,
Page
4
of
6
Fensulfothion
OP
Quelea
0.24
0.42
2
308.35
1.202
256.53
Fenthion
OP
Mallard
5.94
44.0
1
278.32
1.25
222.66
Fenthion
OP
House
sparrow
5.6
2.40
2
278.32
1.25
222.66
Fenthion
OP
Quelea
1.3
1.80
2
278.32
1.25
222.66
Methamidophos
OP
Starling
10.0
17.8
3
141.13
1.343
105.09
Methamidophos
OP
Red­
winged
Blackbird
1.73
31.6
3
141.13
1.343
105.09
Methiocarb
Carbamate
House
sparrow
18
>
100.0b
2
225.31
0.6
375.52
Methiocarb
Carbamate
Quelea
4.2
100.0
2
225.31
0.6
375.52
Methyl
parathion
OP
Mallard
60.5
53.6
1
263.21
1.358
193.82
Mevinphos
OP
Mallard
4.63
11.1
1
224.15
1.25
179.32
Monocrotophos
OP
Mallard
4.76
30.0
1
223.17
1.3
171.67
Monocrotophos
OP
House
sparrow
1.3
18.0
2
223.17
1.3
171.67
Monocrotophos
OP
Quelea
1.3
4.2
2
223.17
1.3
171.67
Paraquat
Dichloride
Bipyridinium
Mallard
199
600.0
1
257.20
1.25
205.76
Parathion
OP
Mallard
2.34
28.3
1
291.26
1.267
229.88
Parathion
OP
House
sparrow
1.3
1.8
2
291.26
1.267
229.88
Parathion
OP
Quelea
1.8
1.8
2
291.26
1.267
229.88
Phorate
OP
Mallard
2.55
203.0
1
260.38
1.167
223.12
Phosfolan
OP
House
sparrow
2.4
18.0
2
255.28
1.3
196.37
Phosfolan
OP
Quelea
1.8
10.0
2
255.28
1.3
196.37
Phosphamidon
OP
Mallard
3.81
26.0
1
299.69
1.2132
247.02
TEPP
OP
Mallard
3.56
64.0
1
290.20
1.2
241.83
Compound
Class
Species
Oral
LD50
(
mg/
kg)
Dermal
LD50
(
mg/
kg)
Footnotea
Molecular
Weight
Density
Molar
Volume
(
mol/
cm3)

Appendix
H,
Page
5
of
6
Thionazin
OP
Mallard
1.68
7.07
1
248.26
1.207
205.68
Footnotes:

1
Hudson,
R.
H.,
M.
A.
Haegele,
and
R.
K.
Tucker.
1979.
Acute
oral
and
percutaneous
toxicity
of
pesticides
to
mallards:

Correlations
with
mammalian
toxicity
data.
Toxicology
and
Applied
Pharmacology
47:
451­
460.

2
Schafer,
E.
W.,
R.
B
Brunton,
N.
F.
Lockyer,
and
J.
W.
DeGrazio.
1973.
Comparative
toxicity
of
seventeen
pesticides
to
the
quelea,
house
sparrow,
and
redwing
blackbird.
Toxicol.
Appl.
Pharmacol.
26:
154­
157.

3
Schafer,
E.
W.
1984.
MRID
00146286
4
Schaefer,
E.
W.
1972.
The
acute
oral
toxicity
of
369
pesticidal,
pharmaceutical,
and
other
chemicals
to
wild
birds.
Toxicol.

Appl.
Pharmacol.
21:
315­
330.

b
Data
value
was
censored
(
50%
mortality
not
obtained
at
highest
dose)
and
was
not
used
in
the
statistical
analysis.
Appendix
H,
Page
6
of
6
Table
H­
2.
Summary
of
fitted
regression
models
to
predict
dermal
LD50
from
oral
LD50
and
the
chemical
properties
molecular
weight
(
MW),
density,
and
molecular
volume
(
MV).

Model
Included
Dependent
Variables
Adjusted
R­
square
Variables
with
p­
value
<
0.25
1
Logoral,
MW,
density,
MV
0.2575
Logoral
2
Logoral,
MW,
density
0.2678
Logoral
3
Logoral,
MW,
MV
0.2741
Logoral
4
Logoral,
density,
MV
0.2634
Logoral
5
Logoral,
MW
0.2812
Logoral
6
Logoral,
density
0.2762
Logoral
7
Logoral,
MV
0.2677
Logoral
8
Logoral
0.2857
Logoral
Literature
Cited
Mineau,
Pierre.
2002
Estimating
the
probability
of
bird
mortality
from
pesticide
sprays
on
the
basis
of
the
field
study
record.

Environmental
Toxicology
and
Chemistry
21:
1497­
1506.