Document ID: EPA-HQ-ORD-2006-0384-0064
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-12T04:00Z

1
Summary
of
Summary
of
EPA
Ethics
Review
EPA
Ethics
Review
Cain,
W.
(
2004)
Human
Sensory
Irritation
Testing
for
Chloropicrin.
Unpublished
study
prepared
by
Chemosensory
Perception
Laboratory,
Univ.
of
California 

San
Diego
under
Project
No.
PIC­
1.
378
p.
MRID
46443801
Supplemented
by
Watson,
S.
(
2005)
Letter
dated
April
12,
2005,
to
Kelly
White,
EPA,
transmitting
partial
responses
to
EPA
letter
of
March
3,
2005,
seeking
additional
information
about
the
research
reported
in
MRID
46443801.
278
p.
MRID
46566501.
2
Chloropicrin
Study
Summary
Chloropicrin
Study
Summary

Multi­
phase
study
of
sensory
thresholds

Conducted
at
UC­
San
Diego
in
2001­
04

UC­
SD
held
a
FWA
from
OHRP

Overseen
by
UC­
SD
Human
Subjects
Committee

Original
submission
had
many
gaps
in
documentation
of
ethical
conduct

Supplement
was
disorganized,
but
filled
the
key
gaps
3
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"

1.
Value

Explores
the
lower
threshold
of
human
sensitivity
to
chloropicrin,
and
the
relationship
between
sensory
awareness
of
chloropicrin
and
potential
effects
of
exposure
to
it

Information
is
of
potential
value
in
assessing
bystander
and
worker
exposure
and
risks

Funded
by
Chloropicrin
Manufacturers
Task
Force

Submitted
to
EPA
and
CDPR
2.
Scientific
Validity:
Defer
to
others
4
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"
­
2
3.
Subject
Selection

127
subjects;
25
participated
more
than
once

Mostly
college
students,
men
and
women
18­
35

Well­
documented
screening
factors
excluded
pregnant
females,
and
were
otherwise
consistent
with
the
scientific
goals
of
the
study.


Racial
make­
up
of
the
subject
group
closely
matches
the
demographics
of
the
student
population
at
UC­
SD

No
indication
that
any
members
of
particularly
susceptible
groups
were
recruited.
5
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"
­
3
4.
Risk­
Benefit
Ratio

Risks
characterized
as
irritation
in
the
nose,
throat,
and
eyes
that
could
be
sharp
enough
to
cause
blinking
and
tearing,
but
expected
to
be
short
lasting

Dose
levels
set
well
below
those
reported
to
cause
significant
adverse
effects,
and
consistent
with
standards
for
occupational
exposure
set
by
ACGIH
and
OSHA

Potential
societal
benefits
discussed
at
length
in
the
study
report,
and
briefly
in
the
IC
materials

No
discussion
of
how
expected
societal
benefits
were
weighed
against
risks
to
subjects
6
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"
­
4
5.
Independent
Ethics
Review

Overseen
by
the
UC­
SD
Human
Subjects
Committee,
an
IRB
registered
with
OHRP

The
report
does
not
mention
the
Common
Rule

Compliance
asserted
with
the
requirements
of
the
Human
Research
Protections
Program
of
the
UC­
SD

During
the
period
of
this
research
UC­
SD
held
a
Federal­
Wide
Assurance
from
OHRP
7
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"
5
6.
Informed
Consent

Consent
process
summarized
in
the
report,

cited
an
SOP
not
provided

All
subjects
asserted
to
have
provided
informed
consent

IC
materials
included
in
the
report
met
all
Common
Rule
requirements
8
Chloropicrin
Study
Chloropicrin
Study
"
Framework
Framework"
­
6
7.
Respect
for
Subjects

Subject
privacy
was
protected

Subjects
were
free
to
withdraw
at
any
time

Some
did
leave
the
chamber
during
some
exposures
9
Chloropicrin
Study:

Chloropicrin
Study:

Prevailing
Standards
Prevailing
Standards

Conducted
in
US
in
2001­
04
at
UC­
SD

Cites
and
asserts
compliance
with
UC­
SD
Human
Research
Protection
Program

UC­
SD
held
Federal­
Wide
Assurance
at
time
of
research,
promising
full
compliance
with
Common
Rule

Common
Rule
and
FIFRA
§
12(
a)(
2)(
P)
are
applicable
standards
10
Comparison
to
Prevailing
Standards
Comparison
to
Prevailing
Standards

No
noteworthy
ethical
deficiencies
are
apparent
when
this
study
is
reviewed
against
the
standards
of
the
Common
Rule

No
noteworthy
deficiencies
are
apparent
with
this
study
is
reviewed
against
the
requirements
of
FIFRA
§
12(
a)(
2)(
P)
11
Chloropicrin
Study
Summary
Chloropicrin
Study
Summary

Remaining
gaps
in
the
record
are
not
"
clear
and
convincing
evidence"

No
evidence
that
the
research
was
fundamentally
unethical

§
26.1703
does
not
prohibit
reliance
on
this
study

All
subjects
were
at
least
18

Female
subjects
were
tested
to
ensure
they
were
not
pregnant

No
noteworthy
ethical
deficiencies
relative
to
prevailing
standards
12
Charge
Questions
Charge
Questions

Is
there
clear
and
convincing
evidence
that
the
conduct
of
the
Cain
study
was
fundamentally
unethical?

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?