U.
S.
ENVIRONMENTAL
PROTECTION
AGENCY
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
(
OPPTS)
1200
Pennsylvania
Avenue,
N.
W.
,
Washington,
D.
C.
20460
OMB
REVIEW
UNDER
EXECUTIVE
ORDER
12866
DOCUMENTATION
OF
CHANGES
MADE
DURING
OMB
REVIEW
Title
of
Action:
Human
Testing;
Advance
Notice
of
Proposed
Rulemaking
Docket
#:
OPP­
2003­
0132
FRL#:
7302­
8
RIN
#:
2070­
AD57
This
action
was
submitted
to
the
Office
of
Management
and
Budget
(
OMB)
for
review
under
Executive
Order
12866,
which
is
entitled
Regulatory
Planning
and
Review
(
58
FR
51735,
October
4,
1993).
According
to
section
6(
a)(
3)(
E)
of
the
Executive
Order,
whenever
the
Agency
makes
publicly
available
a
regulatory
action
that
was
reviewed
under
Executive
Order
12866,
the
Agency
is
also
required
to
make
certain
information
available
to
the
public.
[
Please
check
the
appropriate
box
below:]

G
For
this
regulatory
action,
no
substantive
changes
were
made
to
the
document.
Accordingly,
this
rulemaking
docket
contians
a
copy
of
the
information
that
was
provided
to
OMB's
Office
of
Information
and
Regulatory
Affairs
(
OIRA)
for
review
under
to
the
Executive
Order,
i.
e.,
the
text
of
the
draft
regulatory
action
and
an
assessment
of
the
potential
costs
and
benefits;
as
well
as
additional
information
required
for
those
actions
that
are
determined
to
be
significant
under
section
3(
f)
of
the
Executive
Order.


For
this
regulatory
action,
substantive
changes
were
made
to
the
document.
Accordingly,
this
rulemaking
docket:

1)
contains
a
copy
of
the
information
that
was
provided
to
OMB's
Office
of
Information
and
Regulatory
Affairs
(
OIRA)
for
review
under
to
the
Executive
Order,
i.
e.,
the
text
of
the
draft
regulatory
action
and
an
assessment
of
the
potential
costs
and
benefits;
as
well
as
additional
information
required
for
those
actions
that
are
determined
to
be
significant
under
section
3(
f)
of
the
Executive
Order;
and
2)
the
attached
information
identifies
any
substantive
changes
that
were
made
to
the
draft
regulatory
text
that
was
submitted
to
OIRA,
and
which
subsequently
published.

Additional
Comments:
See
attached
document,
redlined
to
highlight
changes
made
during
OMB
review
under
EO
12866.

If
you
have
any
questions
about
this
action,
please
call
the
contact:
Name:
Bill
Jordan
E­
Mail:
jordan.
william@
epa.
gov
Phone:
703­
305­
1049
RCS
­
OMB­
7f
(
04/
15/
97)
FILE
NAME:
HS­
ANPR
3­
28­
03­
EO12866revisions:
Redlined
to
show
changes
1
Deliberative
 
Do
Not
Cite
or
Quote
2
ENVIRONMENTAL
PROTECTION
AGENCY
3
[
RIN:
2070­
AD57]
4
[
OPP­
2003­
0132;
FRL­
XXXX­
X]
5
Human
Testing;
Advance
Notice
of
Proposed
Rulemaking
6
AGENCY:
Environmental
Protection
Agency
(
EPA).
7
ACTION:
Notice.
8
____________________________________________________________
9
SUMMARY:
This
notice
announces
EPA's
plan
to
conduct
rulemaking
about
criteria
10
and
standards
EPA
would
apply
in
deciding
the
extent
to
which
it
will
consider
or
rely
11
on
various
types
of
research
with
human
subjects
to
support
its
actions.
This
notice
12
also
initiates
the
rulemaking
process
by
requesting
public
comments
and
suggestions
13
on
a
broad
range
of
issues
relating
to
this
subject.
14
DATES:
Comments
must
be
received
on
or
before
[
insert
date
[
ninety]
days
after
date
15
of
publication
in
the
Federal
Register].
16
ADDRESSES:
Submit
your
comments,
identified
by
docket
ID
number
OPP­
2003­
0132,
17
online
at
http://
www.
epa.
gov/
edocket
(
EPA

s
preferred
method)
or
mailed
to
the
Public
18
Information
and
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
19
Environmental
Protection
Agency,
(
7502C),
1200
Pennsylvania
Ave.,
NW,
Washington,
20
DC,
20460­
0001.
For
additional
submission
methods
and
detailed
instructions,
go
to
21
Unit
I.
C.
of
the
SUPPLEMENTARY
INFORMATION
section.
22
FOR
FURTHER
INFORMATION
CONTACT:
William
L.
Jordan,
Mailcode
7501­
C,
23
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
24
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
703­
305­
1049
fax
number:
703­
25
308­
4776;
e­
mail
address:
jordan.
william@
epa.
gov.
26
SUPPLEMENTARY
INFORMATION:
27
This
Advance
Notice
of
Proposed
Rulemaking
(
ANPR)
is
organized
into
four
28
Units.
Unit
I
contains
"
General
Information"
about
the
applicability
of
this
Notice,
how
29
to
obtain
additional
information,
how
to
submit
comments
in
response
to
the
request
for
30
comments,
and
certain
other
related
matters.
Unit
II
provides
background
and
historic
31
information
pertaining
to
human
subject
research.
Unit
III
describes
the
rulemaking
32
process,
identifies
relevant
statutory
provisions,
and
requests
public
comments
and
33
suggestions
on
a
broad
range
of
issues
related
to
the
Agency's
consideration
of
or
34
reliance
on
research
with
human
subjects.
Unit
IV
describes
procedures
followed
in
the
35
development
of
this
ANPR
and
certain
statutes
and
Executive
Orders
that
the
public
36
may
wish
to
consider
in
preparing
comments.
37
I.
General
Information
38
A.
Does
this
Action
Apply
to
Me?
39
2
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
40
particular
interest
to
those
who
conduct
testing
of
substances
regulated
by
EPA.
Since
41
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
42
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
43
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
44
under
FOR
FURTHER
INFORMATION
CONTACT.
45
B.
How
Can
I
Get
Copies
of
This
Document
and
Other
Related
Information?
46
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
47
docket
identification
(
ID)
number
OPP­
2003­
0132.
The
official
public
docket
consists
of
48
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
49
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
50
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
51
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
52
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
53
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
54
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
55
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305­
5805.
56
2.
Electronic
access.
You
may
access
this
Federal
Register
document
57
electronically
through
the
EPA
Internet
under
the
"
Federal
Register"
listings
at
58
http://
www.
epa.
gov/
fedrgstr/.
A
frequently
updated
electronic
version
of
40
CFR
part
59
[
insert
number]
is
available
at
60
http://
www.
access.
gpo.
gov/
nara/
cfr/
cfrhtml_
00/
Title_
40/
40cfr[
insert
part
61
number]_
00.
html,
a
beta
site
currently
under
development.
62
An
electronic
version
of
the
public
docket
is
available
through
EPA

s
electronic
63
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
64
http://
www.
epa.
gov/
edocket
to
submit
or
view
public
comments,
access
the
index
listing
65
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
66
public
docket
that
are
available
electronically.
Once
in
the
system,
select
"
search,"
then
67
key
in
the
appropriate
docket
ID
number.
68
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
69
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
70
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
71
EPA

s
electronic
public
docket.
EPA

s
policy
is
that
copyrighted
material
will
not
be
72
placed
in
EPA

s
electronic
public
docket
but
will
be
available
only
in
printed,
paper
73
form
in
the
official
public
docket.
To
the
extent
feasible,
publicly
available
docket
74
materials
will
be
made
available
in
EPA

s
electronic
public
docket.
When
a
document
is
75
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
76
document
is
available
for
viewing
in
EPA

s
electronic
public
docket.
Although
not
all
77
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
78
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
79
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
80
docket
materials
through
EPA

s
electronic
public
docket.
81
3
For
public
commenters,
it
is
important
to
note
that
EPA

s
policy
is
that
public
82
comments,
whether
submitted
electronically
or
on
paper,
will
be
made
available
for
83
public
viewing
in
EPA

s
electronic
public
docket
as
EPA
receives
them
and
without
84
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
85
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
86
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
87
comment
that
is
placed
in
EPA

s
electronic
public
docket.
The
entire
printed
comment,
88
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
89
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
90
be
transferred
to
EPA

s
electronic
public
docket.
Public
comments
that
are
mailed
or
91
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA

s
electronic
public
docket.
92
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
93
placed
in
EPA

s
electronic
public
docket
along
with
a
brief
description
written
by
the
94
docket
staff.
95
C.
How
and
To
Whom
Do
I
Submit
Comments?
96
You
may
submit
comments
electronically,
by
mail,
or
through
hand
97
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
98
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
99
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
100
the
close
of
the
comment
period
will
be
marked
"
late."
EPA
is
not
required
to
consider
101
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
102
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
103
or
e­
mail
to
submit
CBI
or
information
protected
by
statute.
104
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
unit,
105
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
e­
mail
address
106
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
107
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
108
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
109
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
110
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
111
your
comment.
EPA

s
policy
is
that
EPA
will
not
edit
your
comment,
and
any
identifying
112
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
113
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA

s
114
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
115
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
116
comment.
117
i.
EPA
Dockets.
Your
use
of
EPA

s
electronic
public
docket
to
submit
comments
118
to
EPA
electronically
is
EPA

s
preferred
method
for
receiving
comments.
Go
directly
to
119
EPA
Dockets
at
http://
www.
epa.
gov/
edocket,
and
follow
the
online
instructions
for
120
submitting
comments.
Once
in
the
system,
select
"
search,"
and
then
key
in
docket
ID
121
number
OPP­
2003­
0132.
The
system
is
an
"
anonymous
access"
system,
which
means
122
EPA
will
not
know
your
identity,
e­
mail
address,
or
other
contact
information
unless
you
123
provide
it
in
the
body
of
your
comment.
124
ii.
E­
mail.
Comments
may
be
sent
by
e­
mail
to
opp­
docket@
epa.
gov,
Attention:
125
Docket
ID
Number
OPP­
2003­
0132.
In
contrast
to
EPA

s
electronic
public
docket,
126
4
EPA

s
e­
mail
system
is
not
an
"
anonymous
access"
system.
If
you
send
an
e­
mail
127
comment
directly
to
the
docket
without
going
through
EPA

s
electronic
public
docket,
128
EPA

s
e­
mail
system
automatically
captures
your
e­
mail
address.
E­
mail
addresses
that
129
are
automatically
captured
by
EPA

s
e­
mail
system
are
included
as
part
of
the
comment
130
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA

s
electronic
131
public
docket.
132
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
you
133
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
134
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
135
any
form
of
encryption.
136
2.
By
mail.
Send
your
comments
to:
Public
Information
and
Records
Integrity
137
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency
138
(
7502C),
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC,
20460­
0001,
Attention:
139
Docket
ID
Number
OPP­
2003­
0132.
140
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
Public
Information
and
141
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
142
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
143
VA.,
Attention:
Docket
ID
Number
OPP­
2003­
0132.
Such
deliveries
are
only
accepted
144
during
the
docket

s
normal
hours
of
operation
as
identified
in
Unit
I.
A.
1.
145
D.
How
Should
I
Submit
CBI
To
the
Agency?
146
Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
147
EPA

s
electronic
public
docket
or
by
e­
mail.
You
may
claim
information
that
you
submit
148
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
149
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
150
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
151
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
152
forth
in
40
CFR
part
2.
153
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
154
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
155
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA

s
electronic
public
156
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
157
outside
of
the
disk
or
CD
ROM
clearly
that
it
does
not
contain
CBI.
Information
not
158
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA

s
electronic
public
docket
159
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
160
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
161
CONTACT."
162
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
163
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
164
1.
Explain
your
views
as
clearly
as
possible.
165
2.
Describe
any
assumptions
that
you
used.
166
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
167
5
your
views.
168
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
169
that
you
provide.
170
5.
Provide
specific
examples
to
illustrate
your
concerns.
171
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
172
76.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
173
87.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
control
number
174
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
175
may
also
provide
the
name,
date,
and
Federal
Register
citation.
176
II.
Introduction
177
A.
Background
on
Federal
Standards
for
Conducting
Human
Research
178
Over
the
years,
scientific
research
with
human
subjects
has
provided
much
179
valuable
information
to
help
characterize
and
control
risks
to
public
health,
but
its
use
180
has
also
raised
particular
ethical
concerns
for
the
welfare
of
the
human
participants
in
181
such
research
as
well
as
scientific
issues
related
to
the
role
of
such
research
in
182
assessing
risks.
Society
has
responded
to
these
concerns
by
defining
general
183
standards
for
conducting
human
research.
In
the
United
States,
the
National
184
Commission
for
the
Protection
of
Human
Subjects
of
Biomedical
and
Behavioral
185
Research
issued
in
1979
The
Belmont
Report:
Ethical
Principles
and
Guidelines
for
the
186
Protection
of
Human
Subjects
of
Research.
This
document
can
be
found
on
the
web
at
187
http://
ohsr.
od.
nih.
gov/
mpa/
belmont.
php3
188
http://
ohrp.
osophs.
dhhs.
gov/
humansubjects/
guidance/
belmont.
htm.
189
For
most
federal
agencies
in
the
United
States,
the
principles
of
the
Belmont
190
Report
are
implemented
through
the
Common
Rule,
which
was
developed
191
cooperatively
by
some
17
departments
and
agencies,
including
EPA,
and
which
guides
192
all
research
with
human
subjects
conducted
or
supported
by
these
departments
and
193
agencies
of
the
federal
government.
The
Common
Rule
as
promulgated
by
EPA
(
40
194
CFR
Part
26)
has
guided
human
research
conducted
or
supported
by
EPA
since
it
was
195
put
in
place
in
1991.
196
More
broadly,
the
international
medical
research
community
has
developed
and
197
maintains
ethical
standards
documented
in
the
Declaration
of
Helsinki,
first
issued
by
198
the
World
Medical
Association
in
1964
and
revised
several
times
since
then.
These
199
standards
apply
to
diagnostic
and
therapeutic
medical
research
on
matters
relating
to
200
the
diagnosis
and
treatment
of
human
disease,
and
to
research
that
adds
to
201
understanding
of
the
causes
of
disease
and
the
biological
mechanisms
that
explain
the
202
relationships
between
human
exposures
to
environmental
agents
and
disease.
203
In
addition,
many
public
and
private
research
and
academic
institutions
and
204
private
companies,
both
in
the
United
States
and
in
other
countries,
including
non­
205
federal
U.
S.
and
non­
U.
S.
governmental
organizations,
have
their
own
specific
policies
206
related
to
the
protection
of
human
participants
in
research.
207
Much
of
the
scientific
research
supporting
EPA's
actions,
including
a
significant
208
6
portion
of
the
research
with
human
subjects
submitted
to
the
Agency
or
retrieved
by
the
209
Agency
from
published
sources,
is
conducted
by
this
broader
research
community,
210
without
direct
participation
or
support
by
the
U.
S.
government.
Such
research,
referred
211
to
here
as
"
third
party"
research,
while
it
may
be
governed
by
specific
institutional
212
policies
intended
to
protect
research
participants
or
may
fall
within
the
scope
of
the
213
Declaration
of
Helsinki,
is
not
subject
to
the
Common
Rule.
In
general,
EPA
can
not
214
readily
determine
whether
such
policies
are
consistent
with
or
as
protective
of
human
215
subjects
as
the
Common
Rule,
nor
the
extent
to
which
such
policies
or
standards
have
216
been
followed
in
the
conduct
of
any
particular
study.
Thus
even
well­
conducted
third­
217
party
human
studies
may
raise
difficult
questions
for
the
Agency
when
it
seeks
to
218
determine
their
acceptability
for
consideration.
219
B.
Human
Research
Issues
in
EPA's
Pesticide
Program
220
Questions
about
the
Agency's
consideration
of
and
reliance
on
third­
party
221
human
research
studies
have
arisen
most
notably,
but
not
exclusively,
in
EPA's
222
pesticides
program.
Under
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
223
(
FIFRA),
EPA
may
require
pesticide
companies
to
conduct
studies
with
human
224
subjects,
for
example,
to
measure
potential
exposure
to
pesticide
users
or
to
workers
225
and
others
who
re­
enter
areas
treated
with
pesticides,
and
to
evaluate
the
226
effectiveness
of
pesticide
products
intended
to
repel
insects
and
other
pests
from
227
human
skin.
In
addition,
EPA
sometimes
encourages
other
research
with
human
228
subjects,
including
tests
of
the
potential
for
some
pesticides
 
generally
those
designed
229
for
prolonged
contact
with
human
skin
 
to
irritate
or
sensitize
human
skin,
and
tests
of
230
the
metabolic
fate
of
pesticides
in
the
human
system.
These
latter
studies
typically
231
precede
monitoring
studies
of
agricultural
workers
and
others
to
protect
them
from
232
exposure
to
potentially
dangerous
levels
of
pesticide
residues.
233
In
addition
to
these
kinds
of
research
which
have
been
required
or
encouraged
234
by
EPA,
other
kinds
of
human
studies
involving
human
subjects
intentionally
exposed
235
to
with
pesticides
have
occasionally
been
submitted
to
the
agency
voluntarily.
Among
236
these
voluntarily
submitted
studies
have
been
tests
involving
intentional
dosing
of
237
human
subjects
to
establish
a
No
Observed
Adverse
Effect
Level
(
NOAEL)
or
No
238
Observed
Effect
Level
(
NOEL)
for
systemic
toxicity
of
certain
pesticides
to
humans.
239
Before
passage
of
the
Food
Quality
Protection
Act
in
1996,
submission
of
such
studies
240
was
rare.
EPA
considered
and
relied
on
human
NOAEL/
NOEL
studies
in
a
few
241
regulatory
decisions
on
pesticides
made
prior
to
1996.
Since
the
passage
of
FQPA,
242
submission
of
these
types
of
studies
to
the
Office
of
Pesticide
Programs
has
increased;
243
the
Agency
has
received
some
twenty
studies
of
this
kind
since
1996.
244
In
response
to
concerns
about
human
testing
expressed
in
a
report
of
a
non­
245
governmental
advocacy
organization,
the
Environmental
Working
Group,
in
July,
1998,
246
the
Agency
began
a
systematic
review
of
its
policy
and
practice.
In
a
press
statement
247
on
July
28,
1998,
EPA
noted
that
it
had
not
relied
on
any
such
studies
in
any
final
248
decisions
made
under
FQPA;
this
remains
true
today.
249
In
further
response
to
growing
public
concern
over
pesticide
research
with
250
human
subjects,
EPA
convened
an
advisory
committee
under
the
joint
auspices
of
the
251
EPA
Scientific
Advisory
Board
(
SAB)
and
the
FIFRA
Scientific
Advisory
Panel
(
SAP)
to
252
7
1
The
Agency's
press
release
on
this
subject
is
on
the
web
at
http://
yosemite.
epa.
gov/
opa/
admpress.
nsf/
b1ab9f485b098972852562e7004dc686/
c232a45f54737
17085256b2200740ad4?
OpenDocument
In
early
2002
various
parties
from
the
pesticide
industry
filed
a
petition
with
the
U.
S.
Court
of
Appeals
for
the
District
of
Columbia
for
review
of
EPA's
December
2001press
release.
These
parties
argued
that
the
Agency's
interim
approach
constituted
a
"
rule"
promulgated
in
violation
of
the
procedural
requirements
of
the
Administrative
Procedure
Act
and
the
Federal
Food,
Drug,
and
Cosmetic
Act.
The
court
has
denied
motions
concerning
emergency
relief
and
other
matters,
briefs
have
been
filed,
and
oral
argument
of
the
merits
of
the
case
is
scheduled
for
March
2003.
[
Folded
UNCHANGED
into
the
text.]
address
issues
of
the
scientific
and
ethical
acceptability
of
such
research.
This
253
advisory
committee,
known
as
the
Data
from
Testing
of
Human
Subjects
Subcommittee
254
(
DTHSS),
met
in
December
1998
and
November
1999,
and
completed
its
report
in
255
September,
2000.
Their
report
is
available
in
the
Docket
cited
above
in
this
notice,
and
256
on
the
web
at:
http://
www.
epa.
gov/
science1/
pdf/
ec0017.
pdf
257
The
DTHSS
advisory
committee
heard
many
comments
at
their
two
public
258
meetings,
and
further
comments
have
been
submitted
in
response
to
their
published
259
report.
No
clear
consensus
260
emerged
from
the
advisory
committee
process
on
the
acceptability
of
NOAEL
or
NOEL
261
studies
of
systemic
toxicity
of
pesticides
to
human
subjects,
and
significant
differences
262
of
opinion
remain
on
both
their
scientific
merit
and
ethical
acceptability.
A
vigorous
263
public
debate
continues
about
the
extent
to
which
EPA
should
accept,
consider,
or
rely
264
on
third­
party
intentional
dosing
human
toxicity
studies
with
pesticides.
265
C.
EPA's
Current
Agency­
wide
Focus
on
Human
Research
Issues
266
EPA
is
now
interested
in
addressing
these
issues
more
broadly,
and
in
all
267
Agency
programs.
In
December,
2001,
EPA
asked
the
advice
of
the
National
Academy
268
of
Sciences
(
NAS)
on
the
many
difficult
scientific
and
ethical
issues
raised
by
this
269
debate,
and
also
stated
the
Agency's
interim
approach
on
third­
party
intentional
dosing
270
human
subjects
studies.
1
The
Agency's
press
release
on
this
subject
is
on
the
web
at
271
http://
yosemite.
epa.
gov/
opa/
admpress.
nsf/
b1ab9f485b098972852562e7004dc686/
c232
272
a45f5473717085256b2200740ad4?
OpenDocument.
At
that
time
the
Agency
273
committed
that
when
it
receives
the
NAS
report,
"
EPA
will
engage
in
an
open
and
274
participatory
process
involving
federal
partners,
interested
parties
and
the
public
during
275
its
policy
development
and/
or
rule
making
regarding
future
acceptance,
consideration
276
or
regulatory
reliance
on
such
human
studies."
Since
making
that
commitment,
EPA
277
has
decided
to
initiate
a
rulemaking
process
by
issuing
this
notice.
278
In
early
2002
various
parties
from
the
pesticide
industry
filed
a
petition
with
the
279
U.
S.
Court
of
Appeals
for
the
District
of
Columbia
for
review
of
EPA's
December
2001
280
press
release.
These
parties
argued
that
the
Agency's
interim
approach
constituted
a
281
"
rule"
promulgated
in
violation
of
the
procedural
requirements
of
the
Administrative
282
Procedure
Act
and
the
Federal
Food,
Drug,
and
Cosmetic
Act.
The
court
has
denied
283
motions
concerning
emergency
relief
and
other
matters,
briefs
have
been
filed,
and
oral
284
8
argument
of
the
merits
of
the
case
occurred
on
March
17,
2003.
285
Under
a
contract
with
EPA,
the
NAS
has
convened
a
committee
to
provide
the
286
requested
advice.
The
committee
met
in
December
2002,
and
again
in
January
and
287
March
2003.
The
membership,
meeting
schedule,
and
other
information
about
the
work
288
of
this
committee
can
be
found
on
the
NAS
website
at:
289
http://
www4.
nas.
edu/
webcr.
nsf/
5c50571a75df494485256a95007a091e/
9303f725c1590
290
2f685256c44005d8931?
OpenDocument&
Highlight=
0,
EPA.
291
The
committee's
final
report
is
due
in
December
2003.
292
Notwithstanding
these
many
recent
developments
concerning
human
studies,
293
some
things
have
not
changed.
EPA
remains
committed
to
full
compliance
with
the
294
Common
Rule
for
all
research
with
human
subjects
conducted
or
supported
by
the
295
Agency.
The
Agency
is
proud
of
its
record
in
this
regard,
and
proud
of
the
scientific
296
quality
of
the
research
performed
in
its
own
laboratories
and
with
various
partners.
297
This
body
of
research
has
provided
many
important
insights
and
has
contributed
298
significantly
to
the
protection
of
human
health.
The
Agency
will
continue
to
conduct
299
and
support
such
research,
and
to
consider
and
rely
on
its
results
in
Agency
actions.
300
EPA
also
remains
committed
to
scientifically
sound
assessments
of
the
hazards
of
301
environmental
agents,
taking
into
consideration
available,
relevant,
and
appropriate
302
scientific
research.
303
III.
EPA's
Rulemaking
Process
and
Request
for
Public
Comment
304
EPA
intends
to
undertake
notice­
and­
comment
rulemaking
on
the
subject
of
its
305
consideration
of
or
reliance
on
research
involving
human
subjects.
The
Agency
will
306
particularly
focus
on
third­
party
intentional
dosing
human
studies,
but
recognizes
that
307
the
principles
applicable
to
third­
party
studies
may
also
be
relevant
to
studies
308
conducted
or
supported
by
the
federal
government.
The
first
step
in
this
process
is
this
309
advance
notice
of
proposed
rulemaking
which
calls
for
comments
and
suggestions
from
310
all
interested
parties.
The
next
step
the
Agency
would
expect
to
undertake
would
be
to
311
issue
a
proposed
rule
for
public
comment.
In
developing
any
proposed
rule
EPA
will
312
consider
the
advice
in
the
National
Academy
of
Sciences
committee
report,
along
with
313
comments
received
in
response
to
this
notice.
Comments
received
on
any
proposed
314
rule
would
then
be
taken
into
consideration
in
developing
a
final
rule
or
policy.
315
In
general,
the
Agency
expects
that
any
rule
or
policy
coming
out
of
this
process
316
may
do
one
or
more
of
the
following:
317
°
Specify,
if
and
to
the
extent
determined
by
EPA
to
be
appropriate,
thatwhether
318
EPA
would
not
accept,
consider,
or
rely
on
results
from
particular
types
of
319
studies
involving
intentional
dosing
of
human
subjects
or
from
human
studies
320
with
particular
characteristics;
321
°
Establish
minimum
standards
relating
to
the
protection
of
human
subjects
which
322
would
be
required
to
be
met
in
the
design
and
conduct
of
a
study
with
human
323
9
subjects
not
otherwise
precluded
from
consideration,
in
order
for
EPA
to
accept,
324
consider,
or
rely
on
the
results
of
the
study;
325
°
Establish
procedures
for
ensuring
that
any
minimum
standards
for
the
conduct
of
326
third­
party
research
with
human
subjects
had
been
adhered
to
in
the
conduct
of
327
any
such
study
that
EPA
intended
to
accept,
consider,
or
rely
on.
328
A.
Legal
Authority
329
Section
25(
a)
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
330
gives
the
Administrator
authority
to
"
prescribe
regulations
to
carry
out
the
purposes
of
331
[
FIFRA]."
Such
a
rule
would
implement
EPA's
authority
to
require
data
in
support
of
332
registration
of
pesticides
(
see,
for
example,
FIFRA
sections
3(
c)(
1)(
F)
and
3(
c)(
2)(
B))
333
and
to
interpret
the
provision
making
it
unlawful
for
any
person
"
to
use
any
pesticide
in
334
tests
on
human
beings
unless
such
human
beings
(
i)
are
fully
informed
of
the
nature
335
and
purposes
of
the
test
and
of
any
physical
and
mental
health
consequences
which
336
are
reasonably
foreseeable
therefrom,
and
(
ii)
freely
volunteer
to
participate
in
the
337
test."
(
FIFRA
sec.
12(
a)(
2)(
P)).
In
addition,
section
408(
e)(
1)(
C)
of
the
Federal
Food,
338
Drug
and
Cosmetic
Act
(
FFDCA)
authorizes
the
Administrator
to
issue
a
regulation
339
establishing
"
general
procedures
and
requirements
to
implement
this
section."
340
The
Clean
Air
Act
gives
EPA
general
rulemaking
authority
in
42
U.
S.
C.
7601(
a).
341
The
Clean
Water
Act,
33
U.
S.
C.
sec.
1361,
authorizes
the
Administrator
to
promulgate
342
regulations
necessary
to
carry
out
the
Agency's
functions
under
that
Act.
Section
42
343
U.
S.
C.
9615
in
the
Comprehensive
Environmental
Response,
Compensation,
and
344
Liability
Act
authorizes
the
President
to
establish
regulations
to
implement
the
statute;
345
this
authority
has
been
delegated
to
EPA
by
Executive
Order
12580.
The
Emergency
346
Planning
and
Community
Right­
to­
Know
Act
also
contains
a
general
rulemaking
347
provision,
42
U.
S.
C.
11048,
authorizing
the
Administrator
to
promulgate
rules
348
necessary
to
carry
out
the
Act.
The
Resource
Conservation
and
Recovery
Act
349
specifically
authorizes
the
Administrator
to
prescribe
regulations
necessary
to
carry
out
350
EPA's
functions
under
the
Act,
42
U.
S.
C.
6912.
The
Safe
Drinking
Water
Act
contains
351
similar
language,
authorizing
the
Administrator
to
prescribe
such
regulations
"
as
are
352
necessary
and
appropriate"
to
carry
out
EPA's
functions
under
the
Act,
42
U.
S.
C.
300j­
353
9.
In
addition,
EPA
has
authority
under
5
U.
S.
C.
301
and
42
U.
S.
C.
300v­
1(
b).
354
B.
Request
for
Comments
355
Neither
this
notice
nor
the
specific
questions
presented
below
for
public
356
comment
are
intended
to
indicate
that
EPA
now
favors
any
particular
policy
approaches
357
regarding
the
Agency's
consideration
of
or
reliance
on
third­
party
intentional
dosing
358
human
studies.
Similarly,
neither
this
notice
nor
the
specific
questions
presented
359
below
for
public
comment
are
intended
to
indicate
that
EPA
has
decided
on
a
particular
360
scope
for
any
potential
future
rulemaking.
Nor
is
this
notice
intended
to
impede
or
361
otherwise
delay
any
Agency
assessments
or
actions.
Rather,
this
notice
is
designed
to
362
encourage
public
input
from
all
interested
parties
on
a
broad
range
of
issues
that
could
363
help
inform
any
rule
or
policy
that
EPA
eventually
promulgates
or
issues,
respectively.
364
The
Agency
fully
appreciates
the
number,
the
range,
and
the
365
10
interconnectedness
of
the
scientific
and
ethical
concerns
raised
especially
by
366
intentional
dosing
human
studies
of
the
wide
range
of
environmental
agents
addressed
367
by
EPA's
programs.
Reflecting
the
breadth
of
issues
that
have
been
raised
in
the
368
course
of
the
public
debate
to
this
point,
the
Agency
has
identified
a
number
of
specific
369
questions
on
which
it
particularly
invites
comment.
These
questions
are
intended
to
370
help
organize
and
focus
the
discussion,
but
not
to
constrain
it.
Commenters
should
371
feel
free
to
address
any
other
relevant
topics
as
well.
372
4.
Applicability
of
Existing
Standards
373
a.
Is
it
appropriate
to
use
a
standard
intended
to
guide
the
conduct
of
research,
374
(
e.
g.,
the
Common
Rule,
Declaration
of
Helsinki,
or
the
Nuremberg
Code)
to
375
assess
the
acceptability
for
review
of
completed
research?
376
b.
Is
it
appropriate
to
use
a
standard
intended
to
guide
the
conduct
of
377
therapeutic
or
diagnostic
medical
research
or
to
clarify
causes
of
disease,
such
378
as
the
Declaration
of
Helsinki,
to
assess
the
acceptability
for
review
of
other
379
kinds
of
research
without
diagnostic
or
therapeutic
intent,
conducted
with
healthy
380
subjects?
381
c.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
382
dependingindependent
onf
the
type
of
substance
tested
(
e.
g.,
pharmaceutical,
383
pesticide,
pathogen,
or
environmental
contaminant)?
If
sonot,
how
might
the
384
differing
standards
be
applied
when
a
single
substance
has
multiple
uses,
e.
g.,
385
as
both
a
pesticide
and
a
drug?
386
d.
Does
it
matter
who
maintains
a
standard,
or
by
what
process
it
is
maintained?
387
For
example,
would
it
be
appropriate
for
EPA
to
accept
and
apply
a
standard
388
maintained
by
a
private,
non­
governmental
organization,
and
subject
to
change
389
without
public
notice
and
comment
or
U.
S.
Government
endorsement,
as
is
the
390
Declaration
of
Helsinki?
391
e.
Should
the
Agency
extend
the
requirements
of
the
Common
Rule
to
the
392
conduct
of
third­
party
research
with
human
subjects
intended
for
submission
to
393
EPA?
What
are
the
advantages
and
disadvantages
of
conducting
a
rulemaking
394
or
undertaking
other
Agency
action
for
this
purpose
alone,
as
opposed
to
one
395
with
a
broader
scope?
396
5.
Should
the
standard
of
acceptability
vary
depending
on
the
research
design?
397
a.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
398
dependingindependent
onf
whether
the
research
design
involves
intentional
399
exposure?
For
example,
should
the
same
standard
apply
to
research
involving
400
intentional
exposures
to
human
subjects,
to
research
designed
to
follow­
up
401
accidental
exposure,
and
to
studies
of
individuals
occupationally
or
incidentally
402
exposed?
403
b.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
404
dependingindependent
onf
the
level
of
exposure
of
the
human
subjects?
For
405
11
example,
whendoes
it
matter
if
the
level
of
exposure
to
a
chemical
is
below
the
406
Reference
Dose
or
other
established
health
standard
designed
to
protect
the
407
general
public?
Should
the
same
standard
apply
if
intentional
exposure
to
an
408
environmental
pollutant
occurs
at
ambient
levels,
or
at
elevated
levels?
If
409
research
involves
intentional
exposure
to
a
pesticide,
does
it
matter
if
exposure
410
results
from
use
of
the
pesticide
in
conformity
with
approved
label
directions,
or
411
if
the
level
of
exposure
is
below
the
Reference
Dose
or
other
established
health
412
standard
designed
to
protect
the
general
public??
413
c.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
414
dependingindependent
onf
the
pathway
of
exposure?
For
example,
should
the
415
same
standard
apply
when
exposure
is
oral,
or
dermal,
or
by
inhalation?
416
d.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
417
dependingindependent
onf
the
effects
being
evaluated?
For
example,
should
418
the
same
standard
apply
to
a
study
of
localized
skin
irritation
or
dermal
419
sensitization
that
applies
to
a
study
of
systemic
dermal
toxicity?
Should
the
420
same
standard
apply
to
a
study
measuring
transitory
changes
in
blood
chemistry
421
or
levels
of
a
substance
in
urine
that
applies
to
studies
measuring
longer­
lasting
422
changes?
Should
the
same
standard
apply
to
a
study
of
localized
skin
irritation
423
that
applies
to
a
study
of
systemic
dermal
toxicity?
Should
the
same
standard
424
apply
to
studies
measuring
organoleptic
effects,
such
as
taste
or
smell,
that
425
applies
to
studies
of
toxic
effects?
Should
the
same
standard
apply
to
426
measurements
of
toxic
effects
and
to
measurements
through
genomic
or
427
proteomic
assessments?
428
e.
Should
conduct
of
research
in
compliance
with
the
provisions
of
the
Common
429
Rule
or
another
standard
for
the
protection
of
human
subjects
be
accepted
as
430
evidence
of
its
ethical
acceptability?
431
f.
Should
the
Agency
apply
a
different
standard
of
acceptability
toconsider
432
whether
research
which
ishas
been
performed
consistent
with
an
EPA
guideline
433
for
data
development
in
determining
its
acceptability?
For
example,
EPA
has
434
published
guidelines
for
certain
kinds
of
human
studies
currently
required
for
435
pesticide
registration;
should
conduct
of
a
required
study
in
full
compliance
with
436
an
EPA
guideline
be
accepted
as
evidence
of
its
acceptability?
437
g.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
438
dependingindependent
onf
a
study's
statistical
power?
439
h.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
440
depending
on
whether
or
not
a
human
study
design
is
able
to
measure
the
same
441
endpoints
in
humans
that
have
been
observed
in
animal
testing
of
the
same
442
substance?
For
example,
if
the
most
sensitive
adverse
effects
shown
in
animal
443
studies
have
been
detected
through
histopathological
evaluation
of
brain
tissue,
444
is
subsequent
research
involving
intentional
exposure
of
human
subjects
445
acceptable?
446
i.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
to
447
12
intentional
dosing
studies
dependingindependent
onf
whether
there
are
448
alternative
methods
of
obtaining
data
of
comparable
scientific
merit
that
would
449
not
require
deliberate
exposure
of
humans?
If
not,
to
what
extent,
if
any,
should
450
the
cost
of
the
alternate
method
be
a
factor?
451
j.
Should
What
special
considerations,
if
any,
should
the
Agency
apply
a
452
different
standard
of
acceptability
to
studies
involving
children
as
test
453
subjects?
in
judging
the
acceptability
of
studies
when
some
or
all
of
the
subjects
454
are
from
populations
likely
to
be
vulnerable
to
coercion
or
undue
influence,
such
455
as
children,
prisoners,
pregnant
women,
mentally
disabled
persons,
or
456
economically
or
educationally
disadvantaged
persons?
457
3.
Should
the
standard
of
acceptability
vary
depending
on
the
provenance
of
the
458
research?
459
a.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
460
depending
onwithout
regard
to
who
or
what
organization
sponsors
or
supports
461
the
research?
Since
1991,
human
research
conducted
or
supported
by
the
US
462
government
has
been
subject
to
the
Common
Rule.
Should
the
same
standard
463
apply
to
research
conducted
or
supported
by
others?
Should
a
single
standards
464
differ
when
apply
independent
of
whether
the
sponsor
is
a
commercial
465
enterprise,
or
a
non­
profit
organization,
another
government
in
the
United
States
466
(
such
as
state,
tribal,
or
local),
or
the
government
in
another
country?
Should
467
the
same
standard
differ
depending
onapply
without
regard
to
the
test
sponsor's
468
interest
in
a
regulatory
matter
that
could
be
affected
by
EPA's
consideration
of
469
the
data?
470
b.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
471
dependingindependent
onf
who
or
what
organization
conducts
the
research?
472
For
example,
a
research
organization
 
public
or
private
 
holding
a
"
Federal­
Wide
473
Assurance"
from
the
Department
of
Health
and
Human
Services's
Office
of
474
Human
Research
Protections
usually
promises
to
comply
with
the
Common
Rule
475
in
all
its
human
research,
without
regard
to
the
identity
of
the
sponsor
or
476
supporter
of
the
research.
Should
third­
party
work
conducted
by
a
research
477
organization
holding
a
Federal­
Wide
Assurance
be
assessed
by
a
differentthe
478
same
standard
thanthat
applies
to
other
third­
party
human
research?
479
c.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
480
depending
onwithout
regard
to
where
the
research
was
conducted?
For
481
example,
does
it
matter
whether
research
is
conducted
entirely
in
the
United
482
States
or
partially
in
the
United
States?
If
it
is
conducted
outside
the
United
483
States,
does
it
matter
in
what
country
it
is
conducted?
What
are
the
advantages
484
and
disadvantages
of
judging
the
acceptability
of
human
studies
based
on
a
485
single
uniform
standard
versus
prevailing
local
standards
(
e.
g.,
in
different
486
countries)?
487
d.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
488
depending
onwithout
regard
to
the
reasons
the
research
was
conducted?
If
not,
489
how
might
the
Agency
determine
intent?
490
13
e.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
to
491
submitted
research
depending
onwithout
regard
to
who
submitted
it?
For
492
example,
should
the
same
standard
apply
to
submissions
from
regulated
493
industry,
from
public
interest
groups,
from
the
public,
or
from
other
494
governments?
Should
the
Agency
apply
a
differentthe
same
standard
of
495
acceptability
dependingindependent
onf
whether
the
study
was
submitted
496
voluntarily,
or
in
response
to
a
particular
regulatory
requirement
of
EPA?
497
f.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
to
498
human
research
which
is
not
submitted,
but
which
the
Agency
obtains
at
its
own
499
initiative
from
the
scientific
literature
or
other
sources,
dependingindependent
500
onf
how
or
where
EPA
obtains
it?
501
4.
Should
the
standard
of
acceptability
vary
depending
on
EPA's
potential
use
of
502
the
data?
503
a.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
504
depending
on
independent
of
whether
the
results
of
the
study
would
support
a
505
more
or
less
stringent
regulatory
position?
For
example,
should
the
same
506
standard
apply
whether
the
data
indicate
that
the
substance
tested
is
more
risky
507
or
less
risky
than
is
indicated
by
other
available
data?
508
b.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
509
depending
onwithout
regard
to
how
EPA
intends
to
use
the
results
 
e.
g.,
to
510
reduce
or
remove
the
usualtraditional
tenfold
interspecies
uncertainty
factor,
to
511
provide
an
endpoint
for
use
in
calculating
a
Reference
Dose
or
Reference
512
Concentration
for
the
test
substance,
to
provide
a
dose­
response
function
for
513
use
in
quantitative
risk
assessment,
or
for
some
other
purpose?
514
5.
Should
the
standard
of
acceptability
vary
depending
on
EPA's
assessment
of
the
515
risks
and
benefits
of
the
research
to
the
subjects
or
to
society?
516
a.
Should
the
Agency
apply
a
standard
of
acceptability
based
on
a
comparison
517
of
the
anticipated
benefits
of
the
research
in
relation
to
the
risks
to
human
518
subjects,
provided
the
risks
are
minimized
and
informed
consent
is
obtained?
519
ab.
Should
the
Agency
independently
considerassess
the
risks
of
the
research
520
to
the
subjects
and
the
benefits
of
the
research
to
the
research
subjects
or
to
521
society,
or
should
it
defer
to
the
judgment
of
Institutional
Review
Boards
or
522
similar
oversight
panels?
523
bc.
If
EPA
were
to
assess
independently
the
risks
and
benefits
of
research
to
524
thehuman
research
subjects
or
to
society,
on
what
range
of
information
should
it
525
base
its
assessment?
How
might
EPA
obtain
information
relevant
to
such
an
526
assessment?
527
6.
How
should
the
Agency
implement
standards
of
acceptability?
528
a.
To
what
extent
and
how
should
the
submitter
of
research
with
human
subjects
529
14
to
EPA
be
required
to
document
or
otherwise
demonstrate
compliance
with
530
appropriate
standards
for
the
protection
of
human
research
subjects
 
e.
g.,
fully
531
informed
and
fully
voluntary
participation,
and
independent
oversight
of
research
532
design
and
conduct
by
an
Institutional
Review
Board
or
comparable
entity?
533
b.
How
should
the
Agency
determine
compliance
with
an
appropriate
standard
534
for
human
research
data
which
is
not
submitted,
but
which
it
obtains
from
the
535
scientific
literature
or
other
sources?
536
c.
To
what
extent
should
new
standards
be
applied
to
research
which
has
537
already
been
conducted,
or
is
underway?
Should
a
different
standard
be
538
applied
to
such
research?
Does
fairness
require
a
period
of
transition
to
any
539
new
rule
or
standards
of
acceptability,
or
do
other
considerations
override
that
540
factor?
541
d.
Should
the
Agency
apply
a
differentthe
same
standard
of
acceptability
to
542
research
already
submitted
to
or
obtained
by
EPA
and
to
research
newly
543
submitted
to
or
obtained
by
EPA?
Should
previous
submitters
be
allowed
time
to
544
submit
supplemental
information
to
demonstrate
compliance
with
any
new
Does
545
it
matter
if
the
submitted
research
was
conducted
for
the
specific
regulatory
546
purpose
at
hand
or
for
other
purposes
(
even
though
the
study
was
conducted
547
after
EPA
issued
a
policy
on
human
testing)?
Does
fairness
require
a
period
of
548
transition
to
any
new
rule
or
standards
of
acceptability,
or
do
other
549
considerations
override
that
factor?
550
e.
Is
rulemaking
needed
at
all?
Would
it
be
better
to
address
the
issues
551
surrounding
acceptance
of
human
research,
or
some
of
them,
by
other
means,
552
such
as
policy
statements
or
internal
guidelines?
553
IV.
Statutory
and
Executive
Order
Reviews
554
Under
Executive
Order
12866,
entitled
Regulatory
Planning
and
Review
(
58
FR
555
51735,
October
4,
1993),
it
has
been
determined
that
this
advance
notice
of
proposed
556
rulemaking
is
a
"
significant
regulatory
action"
under
section
3(
f)
of
the
Executive
Order.
557
The
Agency
therefore
submitted
this
document
to
OMB
for
the
10­
day
review
period
558
afforded
under
this
Executive
Order.
Any
changes
made
in
response
to
OMB
559
comments
during
that
review
have
been
documented
in
the
public
docket
as
required
560
by
the
Executive
Order.
561
Since
this
advance
notice
of
proposed
rulemaking
does
not
impose
any
562
requirements,
and
instead
seeks
comments
and
suggestions
for
the
Agency
to
consider
563
in
developing
a
subsequent
notice
of
proposed
rulemaking,
the
various
other
review
564
requirements
that
apply
when
an
agency
imposes
requirements
do
not
apply
to
this
565
action.
566
As
part
of
your
comments
on
this
advance
notice
of
proposed
rulemaking
you
567
may
include
any
comments
or
information
that
you
have
regarding
these
requirements.
568
In
particular,
any
comments
or
information
that
would
help
the
Agency
to
assess
the
569
15
potential
impact
of
a
rule
on
small
entities
pursuant
to
the
Regulatory
Flexibility
Act
570
(
RFA)
(
5
U.
S.
C.
601
et
seq.);
to
consider
voluntary
consensus
standards
pursuant
to
571
section
12(
d)
of
the
National
Technology
Transfer
and
Advancement
Act
of
1995
572
(
NTTAA),
Public
Law
104­
113,
section
12(
d)
(
15
U.
S.
C.
272
note);
or
to
consider
573
environmental
health
or
safety
effects
on
children
pursuant
to
Executive
Order
13045,
574
entitled
Protection
of
Children
from
Environmental
Health
Risks
and
Safety
Risks
(
62
575
FR
19885,
April
23,
1997).
The
Agency
will
consider
such
comments
during
the
576
development
of
any
subsequent
notice
of
proposed
rulemaking
as
it
takes
appropriate
577
steps
to
address
any
applicable
requirements.
578
List
of
Subjects
579
Environmental
protection,
protection
of
human
research
subjects
580
Dated:__________________
581
________________________________________
582
Administrator.
583
[
FR
Doc.
01­??????
Filed
??­??­
01;
8:
45
am]
BILLING
CODE
6560­
50­
S
584
