The
EDMVS
The
EDMVS''

Draft
Work
Plan
Draft
Work
Plan
Presentation
to
the
EDMVS,

Presentation
to
the
EDMVS,

December
10,
2003
December
10,
2003
Purpose
of
Today's
Purpose
of
Today's
WorkPlan
WorkPlan
Show
progress
of
EDSP
Show
progress
of
EDSP
Provide
the
status
of
each
assay
Provide
the
status
of
each
assay
Project
what's
next
Project
what's
next
Tier
I
Screening
Battery
Tier
I
Screening
Battery
recommended
for
consideration
by
EDSTAC
recommended
for
consideration
by
EDSTAC
Steroidogenesis
Steroidogenesis
Pubertal
Pubertal
­
female
female
Fish
Screen
Fish
Screen
aka
aka
short
term
fish
reproduction
short
term
fish
reproduction
Amphibian
Metamorphosis
Amphibian
Metamorphosis
Estrogen
/
Androgen
receptor
binding
Estrogen
/
Androgen
receptor
binding
Hershberger
Hershberger
Uterotrophic
Uterotrophic
Alternative
Assays
Alternative
Assays
recommended
for
consideration
by
EDSTAC
recommended
for
consideration
by
EDSTAC
Tier
I
Tier
I
Aromatase
Aromatase
Pubertal
male
Pubertal
male
Adult
14
Adult
14
 
day
intact
male
day
intact
male
Tier
?

Tier
?

In
In
Utero
Utero
through
Lactation
through
Lactation
Tier
II
Assays
Tier
II
Assays
recommended
for
consideration
by
EDSTAC
recommended
for
consideration
by
EDSTAC
Mammalian
2
Mammalian
2­
generation
generation
Avian
2
Avian
2­
gen.
Reproduction
gen.
Reproduction
Amphibian
Development
and
Repro.

Amphibian
Development
and
Repro.

Invertebrate
(

Invertebrate
(
Mysid
Mysid)
Lifecycle
)
Lifecycle
Fish
Lifecycle
Fish
Lifecycle
Tier
I
Assays
Tier
I
Assays
Steroidogenesis
Steroidogenesis
Milestone
Milestone
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
June
June
02
02
­
cell
based
(
H295R)
Dev
by
ORD
cell
based
(
H295R)
Dev
by
ORD
Prevalidation
Prevalidation
­
sectional
testes
sectional
testes
optimization
optimization
 
June
&
Aug
03
June
&
Aug
03
­
multichem
multichem
&
interlab
interlab
In
Lab
In
Lab
­
cell
based
(
H295R)

cell
based
(
H295R)
In
Lab
In
Lab
Validation
Validation
­
inter
inter­
lab
lab
to
lab
June
04
to
lab
June
04
Current
Status
=
dates
presented
to
EDMVS
&

Current
Status
=
dates
presented
to
EDMVS
&

other
information
other
information
Pubertals
Pubertals
 
m&
f
m&
f
Milestone
Milestone
DRP
equivalent
DRP
equivalent
Prevalidation
Prevalidation
­
Single
Dose
Study
Single
Dose
Study
­
Multi
Multi­
chemical
&
multi
chemical
&
multi­
dose
dose
Protocols
Protocols
­
Multi
Multi­
chemical
&
multi
chemical
&
multi­
dose
dose
­
Restricted
Feeding
Study
Restricted
Feeding
Study
Validation
(
inter
Validation
(
inter­
lab)

lab)
Current
Status
Current
Status
 
Dec
01
Dec
01
 
Dec
Dec
01
01
 
Dec
Dec
01
01
Today
Today
 
July
02
July
02
To
lab
Feb
04
To
lab
Feb
04
Fish
Screen
Fish
Screen
Milestones
Milestones
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
Mar
02
Mar
02
Prevalidation
Prevalidation
­
FHM
FHM
 
Mar
02
Mar
02
­
FHM
w/
multi
FHM
w/
multi­
chemicals
chemicals
Report
writing
Report
writing
­
Comparative
Study
Plans:

Comparative
Study
Plans:
 
Mar
Mar
02
02
­
Results:
Comparative
Studies
Results:
Comparative
Studies
Vitellogenin
Vitellogenin
Methods,
FHM
assays
Methods,
FHM
assays
 
Aug
03
Aug
03
Validation
(
inter
Validation
(
inter­
lab)
depends
on
OECD
lab)
depends
on
OECD
Phase
1A
(
OECD)

Phase
1A
(
OECD)
 
Aug
03
Aug
03
Phase
1B
(
OECD)

Phase
1B
(
OECD)
Spring
04
Spring
04
Amphibian
Metamorphosis
Amphibian
Metamorphosis
Milestone
Milestone
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
July
02
July
02
Pre
Pre­
validation
validation
prometamorphosis
prometamorphosis
­
optimize
protocol
(
US)

optimize
protocol
(
US)
Spring
04
Spring
04
­
protocol
demonstration
to
lab
protocol
demonstration
to
lab
Validation
(
inter
Validation
(
inter­
lab
OECD)
TBD
lab
OECD)
TBD
­
Phase
I
(
protocol
optimization)

Phase
I
(
protocol
optimization)
Spring
04
Spring
04
­"
Phase
2
Phase
2"
Plan
Plan
Spring
04
Spring
04
ER
/
AR
binding
ER
/
AR
binding
ICCVAM
ICCVAM
Scientific
Expert
Panel
Scientific
Expert
Panel''
s
May
2002
s
May
2002
retrospective
validation
retrospective
validation
EDMVS
briefed
by
ICCVAM
July
2002
EDMVS
briefed
by
ICCVAM
July
2002
Expert
Panel
Final
Report
Sept
2002
Expert
Panel
Final
Report
Sept
2002
ICCVAM
Final
Report
May
2003
ICCVAM
Final
Report
May
2003
EDSP:
AR
in
lab
(

EDSP:
AR
in
lab
(
preval
preval)
Update
Today
Update
Today
EDSP:
ER
in
lab
(
valid)
Oct
02
EDSP:
ER
in
lab
(
valid)
Oct
02­
Oct
04
Oct
04
Aromatase
Aromatase
Milestones
Milestones
Current
Status
Current
Status
DRP
/
Protocol
DRP
/
Protocol
 
Mar
02
Mar
02
Prevalidation
Prevalidation
­
placental
placental
microsomal
microsomal
assay
assay
 
June
03
June
03
compare
bovine,
human,

compare
bovine,
human,

porcine
uterine
tissue
porcine
uterine
tissue
­
comparison:
human
placental
&

comparison:
human
placental
&

recombinant,
multi
recombinant,
multi
chem
chem
Today
Today
Validation
(
inter
Validation
(
inter­
lab)

lab)
to
lab
Jan
04
to
lab
Jan
04
In
In
Utero
Utero

Lactation
Lactation
Milestone
Milestone
Current
Status
Current
Status
DRP
DRP
 
Dec
Dec
02
02
­
Protocol
review
Protocol
review
 
Mar
02
Mar
02
Prevalidation
Prevalidation
­
Protocol
Demo
Protocol
Demo
Data
Analysis
Data
Analysis
­
Multi
Multi­
chem
chem
study
TBD
study
TBD
Validation
(
inter
Validation
(
inter­
lab)

lab)
TBD
TBD
Tier
II
Assays
Tier
II
Assays
Mammalian
2
Mammalian
2­
generation
generation
Milestone
Milestone
Current
Status
Current
Status
Prevalidation
Prevalidation
One
One­
gen.
Ext.
Protocol
gen.
Ext.
Protocol
 
Dec
Dec
02
02
Propylthiouracil
Propylthiouracil
Study
Study
 
July
02
July
02
One
One­
gen
gen
Ext.
study
Ext.
study
 
June
03
June
03
Validation
(
inter
Validation
(
inter­
lab)
TBD
lab)
TBD
Avian
2
Avian
2­
gen.
Reproduction
gen.
Reproduction
Milestone
Milestone
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
Aug
03
Aug
03
Prevalidation
Prevalidation
­
Avian
Dosing
Study
Plan
Avian
Dosing
Study
Plan
 
Mar
02
Mar
02
­
Avian
species
Comparison
Avian
species
Comparison
Report
writing
Report
writing
­
Avian
Dose
Study
Avian
Dose
Study
In
Lab
In
Lab
­
Protocol
demo
future
Protocol
demo
future
Validation
(
inter
Validation
(
inter­
lab
OECD)
future
lab
OECD)
future
Amphibian
Amphibian
Dev.
&
Repro.

Dev.
&
Repro.

Milestones
Milestones
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
Spring
04
Spring
04
Prevalidation
Prevalidation
­
transferable
protocol
future
transferable
protocol
future
­
multi
multi­
chem
chem
study
future
study
future
Validation
(
inter
Validation
(
inter­
lab)
future
lab)
future
Mysid
Lifecycle
Mysid
Lifecycle
Milestones
Milestones
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
July
02
July
02
Prevalidation
Prevalidation
­
transferable
protocol
transferable
protocol
Spring
04
Spring
04
­
multi
multi­
chem
chem
study
future
study
future
Validation
(
inter
Validation
(
inter­
lab
OECD)
future
lab
OECD)
future
Fish
Lifecycle
Fish
Lifecycle
Milestones
Milestones
Current
Status
Current
Status
DRP/
Protocol
DRP/
Protocol
 
Dec
Dec
02
02
Prevalidation
Prevalidation
­
protocol
demo
protocol
demo
In
Lab
In
Lab
­
multi
multi­
chem
chem
study
future
study
future
Validation
(
inter
Validation
(
inter­
lab
OECD)
future
lab
OECD)
future
Spring/
Summer
2004
Spring/
Summer
2004
Amphibian
DRP
(
Tier
II)

Amphibian
DRP
(
Tier
II)

Amphibian
Screen
protocol
(
Tier
I)

Amphibian
Screen
protocol
(
Tier
I)

Fish
Screen
multi
Fish
Screen
multi­
chemical
results
chemical
results
Fish
Screen
Phase
1B
(
OECD)

Fish
Screen
Phase
1B
(
OECD)

Mysid
Mysid
Transferable
Protocol
Transferable
Protocol
In
In
Utero
Utero
Through
Lactation
Through
Lactation
Avian
Species
Comparison
Results
Avian
Species
Comparison
Results
EPA
Docket
EPA
Docket
www.
epa.
gov/
edocket
www.
epa.
gov/
edocket
June
03
OPPT
June
03
OPPT­
2003
2003­
0016
0016
August
03
OPPT
August
03
OPPT­
2003
2003­
0027
0027
Dec
03
OPPT
Dec
03
OPPT­
2003
2003­
0064
0064
EDSP
website
EDSP
website
www.
epa.
gov/
scipoly/
oscpendo
www.
epa.
gov/
scipoly/
oscpendo
