1
of
5
DRAFT
4/
19/
06
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
HUMAN
STUDIES
REVIEW
BOARD
(
HSRB)
MAY
2­
3,
2006
PUBLIC
MEETING
Tuesday,
May
2,
2006
Holiday
Inn
Hotel
and
Suites
Alexandria­
Historic
District
625
First
Street
Alexandria,
VA
22314
703­
548­
6300
HSRB
WEB
SITE
http://
www.
epa.
gov/
osa/
hsrb/
Docket
Telephone:
(
202)
566
1752
Docket
Number:
EPA­
HQ­
ORD­
2006­
0310
C
8:
30
AM
Introduction
and
Identification
of
Board
Members
 
Celia
Fisher,
Ph.
D.
(
HSRB
Chair)

C
8:
45
AM
Welcome
 
To
be
announced
C
9:
00
AM
Opening
Remarks
 
To
be
announced
C
9:
15
AM
Meeting
Administrative
Procedures
­
Paul
Lewis,
Ph.
D.
(
Designated
Federal
Officer,
HSRB,
EPA)

C
9:
20
AM
Meeting
Process
 
Celia
Fisher,
Ph.
D.
(
HSRB
Chair)

C
9:
30
PM
Science
and
Ethics
of
Chromium
Human
Studies
­
Timothy
McMahon,
Ph.
D.
(
Office
of
Pesticide
Programs,
EPA),
Jonathan
Chen,
Ph.
D.
(
OPP,
EPA)
and
Mr.
John
Carley
(
OPP,
EPA)

C
10:
30
AM
Break
C
10:
45
AM
Public
Comments
C
11:
45
AM
Lunch
C
12:
45
PM
Board
Discussion
Hexavalent
chromium
is
a
component
of
a
pesticide
product
intended
to
be
used
as
a
wood
preservative.
Members
of
the
general
public
may
experience
dermal
exposure
to
residues
of
hexavalent
chromium
remaining
on
wood
treated
with
a
wood
preservative.
Because
chromium
has
caused
allergic
contact
dermatitis
(
ACD)
in
occupational
settings,
EPA
has
determined
that
it
should
assess
the
potential
for
ACD
in
the
general
public
resulting
from
the
use
of
wood
preservatives
containing
chromium.

In
a
meeting
of
the
FIFRA
Scientific
Advisory
Panel
(
SAP)
in
May
2004,
EPA
obtained
independent
peer
review
of
scientific
issues
related
to
the
assessment
of
the
potential
dermal
risk
resulting
from
exposure
to
chromium.
See
www.
epa.
gov/
scipoly/
sap/
2004/
final.
doc
The
Agency
has
carefully
considered
the
report
of
the
SAP,
as
well
as
the
advice
of
EPA
scientists
2
of
5
through
the
steering
committee
of
the
Agency's
Science
Policy
Council.
Taking
all
of
this
into
account,
EPA
has
derived
a
"
sensitization
reference
dose"
(
RfD)
based
on
the
10%
Minimum
Elicitation
Threshold
(
MET
10)
and
use
of
a
10­
fold
uncertainty
factor
for
potential
variability
within
the
human
population
and
other
uncertainties.
See
ADTC
Memorandum,
"
Hexavalent
Chromium
­
Finalization
of
Issues
related
to
Quantitation
of
Dermal
Risk
from
exposure
to
treated
wood
containing
hexavalent
chromium,"
August
31,
2004.

1.
Scientific
considerations
EPA
has
identified
a
study
performed
with
subjects
who
had
documented
sensitivity
to
chromium
(
Nethercott,
et
al.,
1994).
The
study
was
conducted
to
identify
a
level
of
exposure
to
chromium
below
which
dermal
exposure
did
not
appear
to
elicit
an
ACD
response.
Regarding
the
Nethercott
human
study,
the
Agency
has
concluded
that
the
study
contains
information
sufficient
for
assessing
human
risk
resulting
from
potential
dermal
exposure.

Please
comment
on
whether
the
Nethercott
study
is
sufficiently
sound,
from
a
scientific
perspective,
to
be
used
to
estimate
a
safe
level
of
dermal
exposure
to
hexavalent
chromium.

2.
Ethical
considerations
The
Agency
requests
that
the
Board
provide
comment
on
the
following:

a.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
the
Nethercott
study
was
fundamentally
unethical?

b.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
the
study
was
significantly
deficient
relative
to
the
ethical
standards
prevailing
at
the
time
the
research
was
conducted?

C
2:
30
PM
Science
and
Ethics
of
Carbofuran
Human
Studies
 
John
Liccione,
Ph.
D.
(
OPP,
EPA)
and
Mr.
John
Carley
(
OPP,
EPA)

C
3:
30
PM
Break
C
3:
45
PM
Public
Comments
C
4:
30
PM
Board
Discussion
Carbofuran
is
an
N­
methyl
carbamate
(
NMC)
pesticide
whose
primary
toxic
effect
is
neurotoxicity
caused
by
the
inhibition
of
the
enzyme,
acetylcholinesterase,
via
carbamylation
followed
by
rapid
recovery.
Carbofuran
can,
at
sufficiently
high
doses,
lead
to
a
variety
of
clinical
signs.
The
Agency
is
conducting
acute,
aggregate
(
single
chemical,
multi­
route)
and
worker
risk
assessments
of
carbofuran.
In
addition,
carbofuran
is
a
member
of
the
N­
methyl
carbamate
common
mechanism
group
and
is
thus
included
in
the
cumulative
(
multi­
chemical,
multi­
route)
risk
assessment
for
the
NMCs.

1.
Scientific
considerations
The
Agency's
WOE
document
and
DERs
for
carbofuran
describe
the
study
design
and
results
of
a
carbofuran
human
oral
study
and
two
human
dermal
toxicity
studies.
The
WOE
3
of
5
document
also
discusses
the
Agency's
conclusions
that
these
studies
are
useful
in
establishing
points
of
departure,
both
oral
and
dermal,
for
the
single
chemical
assessment
and
in
informing
the
interspecies
uncertainty
factor
for
the
cumulative
assessment.

Please
comment
on
the
scientific
evidence
that
supports
these
conclusions.

C
5:
30
PM
Adjournment
4
of
5
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
HUMAN
STUDIES
REVIEW
BOARD
(
HSRB)
PUBLIC
MEETING
Wednesday,
May
3,
2006
Holiday
Inn
Hotel
and
Suites
Alexandria­
Historic
District
625
First
Street
Alexandria,
VA
22314
703­
548­
6300
HSRB
WEB
SITE
http://
www.
epa.
gov/
osa/
hsrb/
Docket
Telephone:
(
202)
566
1752
Docket
Number:
EPA­
HQ­
ORD­
2006­
0310
C
8:
30
AM
Convene
Meeting
 
Celia
Fisher,
Ph.
D.
(
HSRB
Chair)

C
8:
40
AM
Follow­
up
From
Previous
Day's
Discussion
 
Mr.
William
Jordan
(
OPP,
EPA)

C
8:
50
AM
Board
Discussion
(
continued)

Carbofuran
(
continued)

2.
Ethical
considerations
The
Agency
requests
that
the
Board
provide
comment
on
the
following:

a.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
any
of
the
human
studies
conducted
with
carbofuran
was
fundamentally
unethical?

b.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
the
studies
was
significantly
deficient
relative
to
the
ethical
standards
prevailing
at
the
time
the
research
was
conducted?

C
9:
30
AM
Science
and
Ethics
of
Methyl
Isothiocyanate
(
MITC)
 
Anna
Lowit,
Ph.
D.
(
OPP,
EPA),
Andrew
L.
Rubin,
Ph.
D.,
D.
A.
B.
T.
(
Calif.
Department
of
Pesticide
Regulation,
Calif.
EPA),
and
Mr.
John
Carley
(
OPP,
EPA)

C
10:
30
AM
Break
C
10:
45
AM
Public
Comments
C
11:
30
AM
Lunch
C
12:
30
PM
Board
Discussion
MITC
is
an
irritating
compound
that
has
a
limited
animal
database
for
toxicity
via
inhalation,
the
key
route
of
exposure.
MITC
can
be
used
as
a
pesticide
directly
to
treat
wood
poles,
but
the
major
pathway
of
exposure
to
MITC
is
from
degradation
of
several
fumigant
pesticides
(
i.
e.,
metam
sodium,
metam
potassium,
and
dazomet).
Due
to
its
volatility,
MITC
has
the
potential
to
move
off­
site,
which
can
result
in
exposure
to
bystanders
near
treated
areas
and,
5
of
5
through
ambient
air,
to
people
far
away
from
treated
areas.
Use
of
the
soil
fumigants
also
results
in
exposure
to
those
handling
the
pesticides
or
working
in
treated
fields.

1.
Scientific
considerations
The
Agency's
WOE
document
and
DER
for
MITC
describe
the
study
design
and
results
of
the
MITC
odor
threshold
and
eye
irritation
human
studies.
The
WOE
document
also
discusses
the
Agency's
conclusions
that
the
eye
irritation
study
is
useful
for
the
assessment
of
potential
effects
on
bystanders
and
workers
from
exposures
to
MITC
during
acute
(
1­
day)
intervals.
The
Agency
has
concluded
that
the
odor
threshold
study
is
less
useful
than
the
eye
irritation
study
for
assessing
the
human
health
effects
of
MITC,
since
the
odor
detection
threshold
for
humans
is
higher
than
the
level
that
causes
eye
irritation.
The
Agency
has
decided,
however,
to
use
the
results
of
the
eye
irritation
study
for
assessing
the
inhalation
exposure
of
MITC.

Please
comment
on
the
scientific
evidence
that
supports
this
conclusion.

2.
Ethical
considerations
The
Agency
requests
that
the
Board
provide
comment
on
the
following:

a.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
the
human
eye
irritation
study
with
MITC
was
fundamentally
unethical?

b.
Is
there
clear
and
convincing
evidence
that
the
conduct
of
this
study
was
significantly
deficient
relative
to
the
ethical
standards
prevailing
at
the
time
the
research
was
conducted?

C
2:
30
PM
Board
Writing
Session
C
3:
30
PM
Adjournment
Please
be
advised
that
agenda
times
are
approximate.
For
further
information,
please
contact
the
Designated
Federal
Officer
for
this
meeting,
Paul
Lewis
via
telephone:
(
202)
564­
8381
or
email:
lewis.
paul@
epa.
gov
