Document ID: EPA-HQ-ORD-2006-0187-0119
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-06T04:00Z

The
Human
DDVP
Data
Do
Provide
Sufficient
Scientifically
Sound
Information
to
Warrant
Reduction
of
the
10X
Interspecies
Factor
Thomas
B.
Starr,
PhD
&
Principal
TBS
Associates,
Raleigh
NC
USA
EPA
Human
Studies
Review
Board
Meeting
5
April
2006
 
Arlington
VA
Our
DDVP
Analysis
for
Non­
Pregnant
Adults
°
Makes
Use
of
Comprehensive
Data
Base
NOT
Just
One
Study
or
Dose
at
a
Time
°
Lab
Animals:
138
Dose­
Duration
Data
Points
°
Humans:
77
Dose­
Duration
Data
Points
°
RBC
Cholinesterase
Activity
Expressed
as
%
of
Control
Activity
°
%
Inhibition
Classified
into
3
Categories:

<
10%
 
10%
to
<
20%
 
20%
Figure
1
Percent
Inhibition
of
Red
Blood
Cell
Cholinesterase
in
Adult
Laboratory
Animals
(
Mice,
Rats,
Dogs,
Monkeys)

0.0001
0.001
0.01
0.1
1
10
100
0.01
0.1
1
10
100
1000
Days
Dose
(

mg/

kg)
Inhibition
<
10%

Inhibition
10­
20%

Inhibition
>
20%

DDVP
Lab
Animal
Data:
Non­
Pregnant
Adults
Figure
2
Percent
Inhibition
of
Red
Blood
Cell
Cholinesterase
in
Adult
Humans
0.0001
0.001
0.01
0.1
1
10
100
0.01
0.1
1
10
100
1000
Days
Dose
(

mg/

kg)
Inhibition
<
10%

Inhibition
10­
20%

Inhibition
>
20%

DDVP
Human
Data:
Actual
Non­
Pregnant
Adults
Figure
2a
Percent
Inhibition
of
Red
Blood
Cell
Cholinesterase
in
Adult
Humans
IF
they
are
10X
More
Sensitive
than
Animals
0.0001
0.001
0.01
0.1
1
10
100
0.01
0.1
1
10
100
1000
Days
Dose
(

mg/

kg)
Inhibition
<
10%

Inhibition
10­
20%

Inhibition
>
20%

DDVP
Human
Data:
IF
10X
More
Sensitive
Conclusions
°
Non­
Pregnant
Adult
Humans
are
NOT
10X
More
Sensitive
than
Non­
Pregnant
Adult
Animals
to
RBC
Cholinesterase
Inhibiting
Effects
of
DDVP
°
Humans
Appear
NO
MORE
Sensitive
than
Animals
°
1X
Interspecies
Factor
is
Scientifically
Warranted
°
Not
Scientifically
Defensible
to
Exclude
these
Data
and
their
Implications
from
Full
and
Fair
Consideration