Document ID: EPA-HQ-OPP-2004-0099-0021
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2004-05-06T04:00Z

SAP
General
Comments
Questions
°
Is
there
an
ACD
problem?

 
Questions
1­
3
are
related
to
general
issues
and
methods
 
Cr
VI
in
treated
wood;
question
4
°
ACD
as
a
disease
 
Should
it
be
assessed
in
the
same
manner
or
as
stringently
as
cancer,
reproductive,
neuro,

other
endpoints?

 
Reversible?
Symptoms
are
reversible,

underlying
sensitization
is
not
Underlying
Principles
°
Not
the
content
in
a
material,
but
it
is
the
amount
of
the
material
being
released
(
e.
g.,
Ni
in
jewelry)
(
exposure)

°
Dermal
Dose
metric
(
ug/
cm2)
is
the
preferred
dose
metric
°
Human
Studies
are
highly
preferred
over
animal
studies
for
risk
assessment
°
Examine
materials
on
a
case
by
case
basis.

Current
animal
testing
methods
may
be
overly
conservative
when
used
for
risk
assessment
purposes.

°
There
should
be
an
effort
to
use
tests
that
mimic
actual
human
exposure
and
conditions
SAP
Comments:
LLNA
Assay
°
Objective;
calculate
the
EC3
°
Good
screening
tool
°
Alternative
to
the
Guinea
Pig
°
Minimizing
the
number
of
animals
°
Given
equal
numbers
of
exposures,
there
is
an
exaggeration
of
exposure
(
compared
to
human)

°
With
more
research
on
different
compounds,
then
it
could
be
used
to
determine
potency
for
Induction
°
Good
for
testing
new
chemicals,
where
data
do
not
exist
SAP
Comments:
LLNA
Assay
(
con't)

 
It
is
a
validated
for
hazard
ID,

but
not
validated
for
testing
for
estimates
of
potency
 
Not
validated
for
metals
and
mixtures
SAP
Comments:
Human
Data
°
Strongly
agree
on
the
preference
for
human
data
for
risk
assessment
 
Greater
certainty,
less
uncertainty,
so
fewer
uncertainty
factors
needed
°
For
risk
assessment,
the
vehicle
needs
to
be
consistent
with
exposure
of
chemical
in
question
°
Testing
 
Patch
Test;
the
panel
strongly
suggests
dilution
of
test
article
for
elicitation
threshold
 
Open
Test;
strongly
suggests
this
test
be
developed
and
used
in
human
testing
using
different
times,

anatomical
sites,
different
mass
of
material
SAP
Comments:
Analyses
of
Data
°
Committee
strongly
suggests
using
the
weight
of
evidence
for
analyses
of
materials
or
chemicals
in
ACD
°
Gather
all
information
 
Historical
data
 
SAR/
QSAR
 
Animal
 
Clinical
 
Toxicological
 
Epidemiological
Question
1
R
C
Pleus
A
Jacobs
G
Burleson
N
Monteiro­
Riviere
T
Menne
Question
1:
Induction
°
What
are
the
strengths
and
weaknesses
of
the
proposed
quantitative
approach
for
determination
of
induction
thresholds
to
dermal
sensitizing
chemicals?

°
What
other
approaches
does
the
Panel
feel
are
most
appropriate
for
application
to
quantitative
methods
of
induction
threshold
determination?

°
What
factors
should
be
included
in
the
determination
of
the
magnitude
of
each
uncertainty
factor?
Overall
Conclusion
Q1
°
We
strongly
agree
that
scientific
studies
assessing
for
Elicitation
will
be
protective
of
Induction
°
Do
we
need
data
on
Induction?
Except
where
there
are
no
data
(
new
chemicals),
studies
that
determine
Induction
thresholds
should
not
be
used
for
the
risk
assessment
process.

°
The
LLNA
has
show
promise
as
a
method
to
assess
potency
of
chemicals
and
with
further
development
and
validation
might
be
useful
for
a
risk
assessment
tool
°
We
do
not
endorse
any
particular
method
for
risk
assessment
UF:
Induction
°
Intraspecies:
1­
10,
depends
on
experimental
design
°
Interspecies:
1­
10,
depends
on
experimental
design
°
Matrix/
vehicle:
depending
on
the
matrix,
these
may
be
exaggerated
exposures
(
e.
g.,
LLNA,

Patch
testing)
therefore
the
value
should
range
from
less
than
1
(
e.
g.,
DMSO)
to
10
(
e.
g.,
dexamethasone)

°
Exposure:
need
to
consider
the
total
dose;

depends
on
body
site,
repeated
exposures;
from
less
than
1
to
10
Question
2
What
are
the
strengths
and
weaknesses
of
the
proposed
quantitative
approaches
for
determination
of
elicitation
thresholds
to
dermal
sensitizing
chemicals?
 
Both
MET
and
LLNA
approaches
use
mass/
area
 
For
human
data,
no
interspecies
correction
required
 
For
the
limited
number
of
chemicals
evaluated,

good
correlation
between
the
human
and
animal
data
Strengths
Weaknesses
 
LLNA
approach
°
Limited
data
available
°
Not
sufficiently
developed
for
current
use
in
risk
assessment
related
to
elicitation
 
MET
approach
°
Questions
related
to
methodology
of
patch
testing
 
Subjectivity
in
human
scoring
 
Skin
condition
 
Vehicle
matrix
 
Adjustment
for
sampling
variability
in
the
data
used
to
estimate
the
MET
can
be
addressed
statistically
by
using
standard
confidence
limits
bounds.

 
MET
approach
can
not
be
used
for
new
chemicals
What
other
approaches
does
the
panel
recommend
that
the
EPA
consider?
Which
uncertainty
factors
does
the
Panel
feel
are
the
most
appropriate
for
application
to
quantitative
methods
of
elicitation
threshold
determination?

°
Intraspecies
°
Repeat
Exposures
°
Vehicle/
Matrix
What
factors
should
be
included
in
the
determination
of
the
magnitude
of
each
uncertainty
factor?

°
For
all
uncertainty
factors,
magnitude
should
be
assessed
on
a
case
by
case
basis
°
Intraspecies
factor
should
be
related
to
the
sample
size
and
quality
of
the
patch
test
data
as
well
as
site
of
exposure
and
condition
of
exposed
skin
°
Exposure
factor
should
take
into
account
use
of
chemical,
expected
duration
and
repetition
of
exposures,

and
potential
for
occlusion
°
Vehicle/
Matrix
effects
should
consider
the
nature
of
the
matrix
including
irritants,
penetration
enhancers
and
the
bioavailability
of
chemical
in
the
matrix
Question
3
°
Does
the
panel
agree
that
the
available
scientific
data
suggests
no
significant
difference
in
the
relative
sensitivity
of
children
vs.
adults
to
the
induction
and/
or
elicitation
of
ACD?

Foulds
Menne
Hayes
Handwerger
Jacobs
Expert
Conclusions
°
We
agree
that
there
is
no
significant
difference
in
the
sensitivity
of
children
vs.

adults
to
the
induction/
or
elicitation
of
ACD.

°
There
is
an
adequate
database
on
this
subject
including
several
reviews
in
the
last
10
years.

°
We
will
send
the
studies
EPA
Question
3
Does
the
panel
agree
that
the
scientific
data
suggest
no
difference
in
the
relative
sensitivity
of
children
vs.
adults
to
the
induction
and
/
or
elicitation
of
allergic
contact
dermatitis?

Foulds
Menne
Hayes
Handwerger
Jacobs
Chromate
positive
patch
tests
°
1084
patch
tests
April
2002
to
Feb
2004
°
66
positives
to
Pot
Dichromate
0.5%

°
3%
of
patients
tested
Chromate
positive
patch
tests
66
positives
to
Pot
Dichromate
0.5%

°
34
male
°
32
female
Chromate
positive
patch
tests
66
positives
to
Pot
Dichromate
0.5%

°
Age
range
24
to
86
years
°
Relevance
(
past
or
present)
close
to
100%

°
Isolated
dichromate
reactions
Does
this
mean
that
children
do
not
react
to
Potassium
Dichromate?

°
NO
°
It
depends
upon
the
study
population
tested
and
the
exposure
that
this
population
has.

°
The
threshold
for
patch
testing
children
is
variable
(
Nickel,
Persistent
hand
eczema)
1084
patients
tested
°
30
were
children
under
12
years
of
age
(
Range
4­
12)

°
18
had
relevant
+
ve
patch
tests
°
Nickel
3
°
Thiurams
4
°
Paraphenylendiamine
(
PPD)
6
WHAT
IS
A
RELEVANT
POSITIVE
PATCH
TEST?
A
?

B
?
D
?

C
?
SCIENCE
VS.
ART
E
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
How
common
is
ACD
in
children?

°
Years
of
exposure?

°
Can
one
exposure
be
sufficient
to
cause
induction?
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
There
are
numerous
published
studies
citing
detection
of
ACD
in
children.

°
Hjorth
1981
Contact
dermatitis
in
children
(
Magnusson
(
1975)
118
children
tested,
38
(
32%)
+
ve
reactions)
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
Epstein
WL
(
1961)
+
ve
to
pentadecyl
catechol
°
<
1
8/
27
30%

°
1­
3
12/
24
50%

°
3­
8
28/
37
76%

(
is
this
to
to
with
environmental
exposure?)
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
Wohrl
et
al
(
1995)

°
2776
consecutive
Patch
tests
°
<
10
years
62%
+
ve
°
>
70
years
34.9%
+
ve
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
Klaus
Anderson
°
1000
School
Children
°
Aged
10
­
14
years
°
15%
+
ve
Patch
tests
Is
there
any
evidence
to
suggest
that
children
with
Atopic
Dermatitis
are
more
likely
to
suffer
from
ACD?

°
NO
°
Less
likely
Many
published
studies
to
support
this
Therefore
there
should
be
no
increased
risk
of
children
with
active
atopic
skin
disease
being
at
any
increased
risk
of
ACD
from
chromate
in
treated
woods.

(
Even
when
exposure
might
occur
on
actively
inflamed
skin)
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
children
be
sensitised?

°
THIOMERSAL
°
11%
of
Swedish
Army
Recruits
patch
tested
What
is
the
evidence
that
there
is
a
difference
in
ACD
in
children?

°
Can
one
exposure
induce
sensitisation?
Question
4
Lead:
T
Menne
A
Jacobs
G
Burleson
N
Monteiro­
Riviere
R
C
Pleus
Q4:
Case
Study
°
Please
comment
on
the
methods
used
for
the
derivation
of
the
`
safe'
area
doses
using
the
available
LLNA
data
and
the
human
patch
test
data,
including
the
magnitude
of
the
applied
uncertainty
factors
and
include
a
scientific
rationale
in
support
of
your
position.

°
Please
comment
on
whether
it
is
scientifically
supportable
to
derive
a
separate
`
safe'
area
dose
for
protection
against
induction
of
dermal
sensitization
as
well
as
elicitation
in
sensitized
individuals
by
hexavalent
chromium.
LLNA
data
°
There
are
a
number
of
well
designed
human
studies
in
sensitized
individuals,

therefore
no
need
to
consider
LLNA
studies
for
the
derivation
of
the
`
safe'
area
dose
°
LLNA
assays
has
not
been
validated
for
assessing
metals
and
therefore
not
applicable
for
Cr
VI
risk
assessment
Exposure
scenario:
Cr
VI
Case
Study
°
Wood
treated
with
ACC
°
Contact
of
treated
wood
used
in
the
construction
of
structural
components
of
outdoor
play
sets
°
Wood
used
in
home
patios,
porches,

decks,
docks,
etc.

°
Bleaching
and
deck
cleaners
°
Exposure
data???
Nethercott
et
al.
1994
°
Background
information
 
ACD
is
a
reversible
condition
 
ACD
will
persist
with
exposure;
when
you
remove
the
source
contact
dermatitis
ceases
(
underlying
contact
allergy
persists)

 
Conducted
in
sensitized
populations
thus
a
sensitive
subpopulation
 
An
elicitation
study
 
T.
R.
U.
E.
test
was
conducted
which
is
more
sensitive
than
other
Patch
Test
systems
for
metals
Critical
Study:
Nethercott
et
al.
1994
°
Large
population
for
Patch
Test
(
54)

°
Good
experimental
design;
several
rounds
of
testing
to
reconfirm
sensitivity;
dose­
response
data
°
Sensitive
pop;
sensitized
to
Cr
VI
°
Hansen
et
al.
(
2002;
2003)
is
supportive,
but
not
large
enough
to
be
considered
by
itself
(~
17)

°
Other
studies
cited
(
see
Hansen
et
al.
2002)
supportive
(
larger
thresholds)

°
Fowler
et
al.
1999
does
not
have
good
experimental
design
and
can
not
be
used
as
the
critical
study
°
A
study
for
4
wks
and
repeated
every
day
as
an
Open
Test
would
have
been
preferred.
However,
Nethercott
et
al.,
was
conducted
under
occlusion
so
more
conservative
Nethercott
et
al.
1994
°
Critical
dose
 
0.088
ug/
cm2
(
4/
54)
or
~
10%
of
the
sensitized
population
chosen
(
MET10)

 
This
is
conservative!

 
0.018
ug/
cm2
was
considered
too
conservative;
disregard
UF
for
Cr
VI
Case
Study
°
Matrix/
vehicle:
0.1
this
is
an
occlusion
study
°
Interspecies:
1
°
Intraspecies:
1
°
Exposure:
3
or
10
Estimated
S­
RfD
0.088
ug/
cm2
=
0.3
to
0.09
ug/
cm2
(
1)
(.
1)
(
1)
(
3
to
10)

[.
3
to
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