The
EDMVS
The
EDMVS''

Draft
Work
Plan
Draft
Work
Plan
Presentation
to
the
EDMVS,

Presentation
to
the
EDMVS,

August
18
August
18­
20,
2003
20,
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
03
&

June
03
&
Today
Today
­
cell
based
(
H295R)

cell
based
(
H295R)
In
Lab
soon
In
Lab
soon
­
multichem
multichem
&
interlab
interlab
to
lab
Sept
03
to
lab
Sept
03
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
to
EDMVS
Dec
03
to
EDMVS
Dec
03
­
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
In
statistical
In
statistical
analysis
analysis
 
July
02
July
02
To
lab
Jan
04
To
lab
Jan
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
In
lab
chemicals
In
lab

­
Comparative
Study
Plans:

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

Phase
1A
(
OECD)
Today
Today
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
optimize
protocol
in
lab
in
lab
­
protocol
demonstration
to
lab
in
04
protocol
demonstration
to
lab
in
04
Validation
(
inter
Validation
(
inter­
lab
OECD)
TBD
lab
OECD)
TBD
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
ICCVAM
Final
Report
May
2003
May
2003
EDSP:
AR
in
lab
(

EDSP:
AR
in
lab
(
preval
preval)
Aug
02
Aug
02
 
Sept
03
Sept
03
EDSP:
ER
in
lab
(
valid)
Aug
EDSP:
ER
in
lab
(
valid)
Aug
02
02
 
May
04
May
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,
Dec
03
Dec
03
porcine
uterine
tissue
porcine
uterine
tissue
­
comparison:

comparison:
microsomal
microsomal
&
"

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

lab)
to
lab
Jan
03
to
lab
Jan
03
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
Dec
03
Dec
03
­
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
Today
Today
Prevalidation
Prevalidation
­
Avian
Dosing
Study
Plan
Avian
Dosing
Study
Plan
 
Mar
02
Mar
02
­
Avian
Dose
Study
in
lab
Avian
Dose
Study
in
lab
to
EDMVS
in
Fall
04
to
EDMVS
in
Fall
04
­
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
December
2003
December
2003
Pubertals
Pubertals
male
and
female
male
and
female
In
In
Utero
Utero
Through
Lactation
Through
Lactation
Update
on
Androgen
Receptor
binding
Update
on
Androgen
Receptor
binding
Aromatase
Aromatase
Adult
Male
(
tentative)

Adult
Male
(
tentative)
Spring
2004
Spring
2004
Amphibian
DRP
Amphibian
DRP
Amphibian
Screen
transferable
protocol
Amphibian
Screen
transferable
protocol
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
