Document ID: EPA-HQ-ORD-2006-0310-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-17T04:00Z

Page
1
of
5
Ha
Ha
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON
D.
C.,
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
14,
2006
MEMORANDUM
Subject:
Transmittal
of
materials
for
review
by
the
Human
Studies
Review
Board.

To:
Paul
Lewis,
Ph.
D.
Designated
Federal
Officer
Human
Studies
Review
Board
Office
of
Science
Advisor
(
8105R)

From:
Jack
E.
Housenger
Associate
Director
Office
of
Pesticide
Programs,
Health
Effects
Division
(
7509C)

Betty
Shackleford
Associate
Director
Office
of
Pesticide
Programs,
Antimicrobials
Division
(
7510C)

The
Agency's
Human
Studies
Review
Board
(
HSRB)
is
scheduled
to
meet
May
2­
4,
2006,
to
address
scientific
and
ethical
issues
surrounding
human
toxicity
studies
involving
two
pesticide
active
ingredients,
carbofuran
and
methyl
isothiocyanate
(
MITC),
and
chromium,
a
constituent
of
wood
preservative
products.
(
Wood
preservatives
are
regulated
as
pesticides
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act.)
By
this
memo
the
Office
of
Pesticide
Programs
(
OPP)
is
transmitting
to
the
HSRB
the
documents
discussed
below.

On
March
21,
2006,
the
Agency
sent
to
the
HSRB
materials
containing
background
information
regarding
EPA
review
policies
and
approaches
and
the
newlyeffective
amended
rules
for
protecting
human
subjects
of
research.
These
materials
may
also
be
useful
in
preparing
for
this
HSRB
meeting.
Page
2
of
5
DOCUMENTS
PROVIDED
TO
THE
HUMAN
STUDIES
REVIEW
BOARD
(
HSRB)
FOR
THE
MAY
2­
4,
2006
MEETING
Introduction
The
Pesticide
Registration
Improvement
Act
(
PRIA)
requires
that
EPA
complete
its
decision­
making
process
on
certain
types
of
applications
to
register
a
pesticide
product
within
specified
amounts
of
time
after
receiving
the
application
for
registration.
In
addition,
PRIA
established
deadlines
for
EPA
to
complete
"
reregistration"
of
pesticide
active
ingredients
that
are
contained
in
pesticide
products
initially
registered
before
1984.
Reregistration
involves
the
systematic
reexamination
of
older
pesticides,
applying
contemporary
scientific
and
regulatory
standards.
When
a
pesticide
active
ingredient
is
approved
for
use
on
food,
EPA
combines
reregistration
with
the
tolerance
reassessment
process
mandated
by
the
Food
Quality
Protection
Act
of
1996
(
FQPA).

Both
MITC
and
carbofuran
are
undergoing
reevaluation
in
the
reregistration
process.
EPA
is
considering
the
human
health
risks
of
chromium
both
in
its
reregistration
program
and
as
part
of
its
review
of
an
application
for
registration
pending
under
FIFRA
and
PRIA.

Types
of
Documents
Provided
to
the
Human
Studies
Review
Board
(
HSRB)
for
the
May
2
­
4,
2006
Meeting
For
each
of
the
human
studies
under
consideration,
the
Agency
has
provided
the
Board
members
with
the
complete
study
report
and
any
supplements
available
to
the
Agency.
Each
of
these
studies
is
assigned
a
unique
identifier,
the
Master
Record
Identifier
or
MRID,
which
OPP
uses
to
manage
documents
in
its
archive.
When
a
company
submits
multiple
documents
pertaining
to
a
single
study,
each
document
is
assigned
a
unique
MRID
as
it
is
received
and
catalogued.
Thus
a
study
with
several
supplements,
such
as
the
MITC
study
to
be
discussed
at
this
meeting,
may
be
associated
with
several
MRIDs.

For
each
study
the
Agency
has
provided
a
review
of
the
ethical
conduct
of
the
study.
Each
ethics
review
identifies
any
deficiencies
noted
in
the
conduct
of
the
specific
study
compared
to
both
current
ethical
standards
and
the
ethical
standards
prevailing
at
the
time
the
research
was
performed.
EPA
has
intentionally
deferred
making
a
final
determination
of
whether
an
individual
study
satisfies
the
ethical
standards
for
acceptability
in
40
CFR
sections
26.1704
 
26.1706,
pending
the
advice
of
the
Board.

For
most
studies,
the
Agency
develops
documents,
called
Data
Evaluation
Records
(
DERs),
containing
a
scientific
review
of
the
study;
the
Board
has
been
provided
with
one
or
more
DERs
for
carbofuran
and
MITC.
DERs
contain
summaries
of
the
study
design,
methods
and
results,
describe
potential
deficiencies,
and
provide
conclusions
about
the
usefulness
of
the
study
in
risk
assessment.
Page
3
of
5
In
addition
to
the
DERs,
OPP
has
prepared
a
"
Weight
of
Evidence"
(
WOE)
memorandum
for
carbofuran
and
MITC
discussing
the
differences
and
similarities
between
the
human
and
animal
responses
to
each
chemical
and
characterizing
the
usefulness
of
the
human
toxicity
studies
for
human
health
risk
assessment.
The
WOE
memos
express
the
Agency's
current
scientific
conclusions
on
which
the
Agency
is
soliciting
the
Board's
comments.
To
maintain
the
historical
record
of
review,
EPA
may,
in
some
cases,
include
a
DER
for
a
study
that
expresses
scientific
conclusions
differing
from
those
in
the
WOE
document.

For
chromium,
EPA
has
provided
a
set
of
documents
which
contain
similar
information
to
DERs
and
WOEs,
but
which
have
a
slightly
different
format
and
presentation,
due
to
the
procedural
history
of
the
EPA's
review
of
this
chemical.
As
noted
above,
chromium
is
a
constituent
in
wood
preservative
products.
EPA
has
concern
about
the
potential
for
chromium
to
elicit
an
allergic
response
in
sensitized
individuals
who
come
in
contact
with
residues
remaining
in
products
made
from
wood
that
has
been
treated
with
chromium­
containing
wood
preservatives.
To
assess
the
risk
of
potential
dermal
exposure,
EPA
reviewed,
among
other
information,
a
study
involving
intentional
exposure
of
sensitized
subjects
to
different
levels
of
chromium,
(
Nethercott
1994).
This
assessment
was
one
of
the
first
assessments
of
this
kind
performed
by
OPP,
and
it
raised
significant
scientific
issues.
Accordingly,
EPA
prepared
a
background
document
for
its
independent,
peer
review
advisory
committee,
the
FIFRA
Scientific
Advisory
Panel
(
SAP).
The
SAP
is
a
federally
chartered
advisory
committee
of
scientific
experts
who
provide
advice
to
EPA
on
scientific
issues
arising
in
connection
with
the
regulation
of
pesticides.
We
are
providing
a
copy
of
the
materials
given
to
the
SAP
for
its
review,
as
well
as
a
copy
of
the
SAP's
final
report.
After
receiving
the
SAP's
recommendations,
EPA
sought
review
and
comment
from
other
Agency
scientists
through
the
steering
committee
of
EPA's
internal
Science
Policy
Council
(
SPC)
to
ensure
consistency
across
programs
in
the
approach
to
regulating
substances
that
are
skin
sensitizers.
Using
the
advice
of
the
SAP
and
the
steering
committee
of
the
SPC,
OPP
developed
a
memorandum
describing
how
OPP
intended
to
use
the
results
of
the
Nethercott
study
to
derive
a
sensitization
Reference
Dose.
This
memorandum,
developed
in
the
Antimicrobials
Division
Toxicity
Endpoint
Selection
Committee
(
ADTC),
is
analogous
to
the
WOE
documents
generated
by
HED.
Page
4
of
5
Table
of
contents
1.
Transmittal
memo
2.
Charge
to
HSRB
3.
Chromium
 
Nethercott
J.,
et
al.,
"
A
study
of
chromium
induced
allergic
contact
dermatitis
with
54
volunteers;
implications
for
environmental
risk
assessment,"
Occup.
Environ.
Med.
1994;
51:
371­
380.
4.
Chromium
 
Ethics
review
by
John
Carley,
USEPA;
April
11,
2006.
5.
Chromium
 
FIFRA
Scientific
Advisory
Panel
Background
Document
[
for
the]
May
4­
6,
2004
Meeting,
by
McMahon,
T.,
et
al.,
USEPA.
6.
Chromium
 
"
Transmittal
of
Minutes
of
the
FIFRA
Scientific
Advisory
Panel
Meeting
Held
May
4­
6,
2004:
A
Consultation
On
Dermal
Sensitization
Issues
For
Exposures
To
Pesticides"
July
1,
2004.
7.
Chromium
 
ADTC
MEMORANDUM:
"
Hexavalent
Chromium
­
Finalization
of
Issues
related
to
Quantitation
of
Dermal
Risk
from
exposure
to
treated
wood
containing
hexavalent
chromium,"
McMahon,
T.,
August
31,
2004.

8.
Carbofuran
  
Arnold,
J.
D.
(
1976)
Evaluation
of
the
Safe
Exposure
Levels
to
Carbamate,
Administered
Orally
to
Healthy
Adult
Normal
Male
Volunteers.
(
Unpublished
study
received
Oct
24,
1979
under
279­
2712;
prepared
by
Quincy
Research
Center,
submitted
by
FMC
Corp.,
Philadelphia,
Pa.;
CDL:
241303­
B)
Accession
no.
241303.
MRID
00092826.
9.
Carbofuran
 
Arnold,
J.
D.
(
1977)
Carbamate
(
Carbofuran)
Human
Dermal
Study.
Final
rept.
(
Unpublished
study
received
Oct
24,
1979
under
279­
2712;
prepared
by
Quincy
Research
Center,
submitted
by
FMC
Corp.,
Philadelphia,
Pa.;
CDL:
241303­
C),
Accession
no.
241303.
MRID
00092827.
10.
Carbofuran
 
Arnold,
J.
D.
(
1978)
Comparison
of
Cholinesterase
Inhibition
and
Effects
of
Furadan
4F
and
FMC
35001
4
EC
(
ACT
152.03).
Rev.
final
rept.
(
Unpublished
study
received
Oct
24,
1979
under
279­
2712;
prepared
by
Quincy
Research
Center,
submitted
by
FMC
Corp.,
Philadelphia,
Pa.;
CDL:
241305­
A)
Accession
no.
241305,
MRID
no.
00092829.
11.
Carbofuran
 
Ethics
review
of
human
oral
study
by
John
Carly,
USEPA;
April
14,
2006
12.
Carbofuran
 
Ethics
review
of
human
dermal
study
by
John
Carly,
USEPA;
April
14,
2006
13.
Carbofuran
 
Ethics
review
of
human
dermal
comparison
study
by
John
Carly,
USEPA;
April
14,
2006
14.
Carbofuran
 
Data
Evaluation
Record
 
human
oral
study
with
carbofuran.
Memo
from
Amal
Mahfouz
to
Jay
Ellenberger
dated
June
26,
1981.
Carbofuran;
EPA
Reg.#
279­
2875
(
Furadan
75
WP)
and
EPA
Reg.
#
279­
2876
(
Furadan
4
F);
also
FMC
35001
4
EC
(
unregistered
Carbofuran
analog).
15.
Carbofuran
 
Data
Evaluation
Record
 
acute
human
dermal
study
(
1977)
with
carbofuran.
Memo
from
Amal
Mahfouz
to
Jay
Ellenberger
dated
June
26,
1981.
Page
5
of
5
Carbofuran;
EPA
Reg.#
279­
2875
(
Furadan
75
WP)
and
EPA
Reg.
#
279­
2876
(
Furadan
4
F);
also
FMC
35001
4
EC
(
unregistered
Carbofuran
analog).
16.
Carbofuran
 
Data
Evaluation
Record
 
acute
human
dermal
study
(
1978)
with
carbofuran.
Memo
from
Amal
Mahfouz
to
Jay
Ellenberger
dated
June
26,
1981.
Carbofuran;
EPA
Reg.#
279­
2875
(
Furadan
75
WP)
and
EPA
Reg.
#
279­
2876
(
Furadan
4
F);
also
FMC
35001
4
EC
(
unregistered
Carbofuran
analog).
17.
Carbofuran
 
Discussion
of
Outside
Peer
Review
Comments
on
the
Carbofuran
RfD,
Memo
from
William
Burnam
to
Tina
Levine
dated
September
11,
1997.
18.
Carbofuran
 
Human
Studies
Review
Board:
CARBOFURAN
Weight
of
Evidence
Presentation
of
Human
and
Animal
Toxicity
Studies
19.
MITC
 
Russell,
M.
J.
and
Rush,
T.
I.
(
1996)
Methyl
Isothiocyanate:
Determination
of
human
olfactory
detection
threshold
and
human
no
observable
effect
level
for
eye
irritation.
Sensory
Testing
Laboratory,
University
of
California
at
Davis.
Report
No.
RR
96­
049B.
September
10,
1996
MRID
44400401.
20.
MITC
 
Supplementary
material
for
Russell
et
al.
(
1996).
MRIDs
46546601,
46558201,
and
46584901.
21.
MITC
 
Ethics
review
by
John
Carley,
April
13,
2006
22.
MITC
 
Data
Evaluation
Record,
Special
Study:
Human
Eye
Irritation
and
Odor
Threshold.
MRIDs
44400401,
46546601,
46558201,
and
46584901.
23.
MITC
 
Human
Studies
Review
Board:
Weight
of
Evidence
Discussion
for
Methyl­
isothiocyanate
(
MITC),
April
13,
2006