Document ID: EPA-HQ-ORD-2006-0310-0027
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-05-01T04:00Z

Re:
EPA
Human
Studies
Review
Board
meeting,
Tuesday
May
2,
2006.

Science
and
Ethics
of
Chromium
Human
Studies.

I
understand
that
my
task
for
the
board
is
primarily
to
be
a
consultant
on
the
scientific
part
of
it
as
no
other
specialists
in
contact
dermatitis
and
patch
testing
is
present.
I
have
read
through
the
ethical
evaluation
and
understand
the
comments.
I
see
my
task
as
primarily
discussing
whether
the
Nethercott
study
is
scientifically
sound
in
the
estimation
of
safe
level
of
dermal
exposure
to
hexavalent
chromium.

Re:
J
Nethercott.

A
study
of
chromium
induced
allergic
contact
dermatitis
with
54
volunteers:
implications
for
environmental
risk
assessment.

Occupational
and
Environmental
Medicine
1994:
51:
371­
380.

The
paper
gives
a
broad
introduction
to
the
phenomenon
contact
allergy
and
contact
allergy
to
chromium.
The
study
is
critical
to
former
studies,
first
of
all
because
of
reading
of
patch
tests
and
application
of
multiple
patch
tests.
The
intention
by
the
study
is
to
use
the
diagnostic
patch
test
in
a
dose
response
manner
to
establish
a
non­
elicitation
level
of
chromate
allergy.
This
study
limits
itself
to
pre­
sensitized
individuals.
That's
to
say
any
kind
of
primary
sensitization
is
not
attempted
and
not
evaluated.
It
only
concerns
people
who
have
been
diagnosed
contact
allergic
to
chromium
by
a
dermatologist.
That's
to
say
that
they
probably
have
had
the
skin
condition
allergic
contact
dermatitis,
which
in
the
first
place
has
led
them
to
the
dermatologist.
In
that
way
the
group
are
selected
and
cannot
be
expected
to
represent
the
general
population,
but
only
the
population
of
chromate
sensitive
with
clinical
symptoms.
This
selection
process
is
clearly
described
and
easy
to
understand.
For
the
diagnosis
of
chromium
allergy
they
used
a
patch
test
system.
They
used
the
newly
developed
patch
test
system
the
True
Test.
This
is
having
several
advantages
as
it
is
prefabricated
and
has
a
defined
content
of
chromium/
cm2.
For
the
reading
of
a
positive
patch
test
there
are
fixed
rules
described
based
on
the
morphology
of
the
test
outcome
in
the
paper.
The
testing
of
the
individuals
is
done
in
a
3­
step
fashion
which
ensures
that
no
patients
have
more
positive
patch
tests
than
necessary
and
the
risk
of
interference
among
the
positive
tests
is
minimalized.
The
planning
and
conduction
of
the
patch
test
is
according
to
high
scientific
level
within
the
speciality
and
only
relatively
few
patch
test
dose­
response
studies
will
make
this
3­
step
procedure.
Most
actually
use
1­
step
procedure.
The
selection
of
the
patch
test
concentrations
is
well
argumented.
Many
studies
will
have
more
steps
in
the
dilution
series.
It
will
probably
not
have
added
further
to
the
scientific
information.

The
study
describes
in
a
clear
way
the
establishment
of
a
minimum
elicitation
level
and
designs
a
dose
response
curve
analysed
according
to
computer
model
data
technique.
The
methodology
is
advanced
in
relation
to
the
time
when
the
study
was
carried
out
and
is
still
in
accordance
with
the
methodologies
employed
today.

The
second
part
of
the
study,
where
the
authors
are
comparing
the
influence
of
total
dose
versus
dose
per
unit
area
has
more
the
character
of
a
pilot
study.

The
final
calculations
of
the
acceptable
exposure
concentration
for
chrome
6
and
3
is
in
my
view
difficult
to
follow.

Conclusion:
The
conduction
and
the
method
used
for
the
Nethercott
study
are
in
accordance
with
the
best
standard
within
the
research
area
of
human
studies
within
contact
dermatitis.
It
is
important
that
the
methodology
used
is
a
close
patch
test
system.
This
is
primarily
developed
as
a
diagnostic
tool.
Within
this
respect
it
is
used
to
define
the
non­
elicitation
level.
This
is
undoubtedly
scientifically
correct.
It
could
be
argued
that
the
study
could
have
been
supplemented
with
studies
simulating
the
intended
exposure
question.
This
could
e.
g.
handling
of
chromium
preserved
wood
under
standardized
circumstances
or
exposure
for
different
time
periods
to
the
skin
with
chromium
preserved
wood.
Such
studies
could
have
excluded
some
of
the
uncertainty
factors
involved
in
the
calculation
of
the
minimum
elicitation
concentration
related
to
real
life
situation.
In
the
evaluation
of
the
patch
test
the
international
accepted
score
for
a
positive
diagnostic
test
is
used.
This
is
of
course
scientifically
correct
but
also
gives
a
conservative
estimate.
It
should
be
remembered
that
from
the
start
it
is
known
that
all
patients
are
chromium
allergic
and
the
very
low
concentrations
are
actually
non­
irritating.
In
recent
European
studies
a
special
reading
scale
is
used
concerning
dose
response
studies,
where
also
weaker
responses
as
e.
g.
follicular
responses
are
judged
as
positives.