DATE:
August
31,
2004
MEMORANDUM
SUBJECT:
Hexavalent
Chromium
­
Finalization
of
Issues
related
to
Quantitation
of
Dermal
Risk
from
exposure
to
treated
wood
containing
hexavalent
chromium
FROM:
Timothy
F.
McMahon,
Ph.
D.
Chair,
Antimicrobials
Division
Toxicity
Endpoint
Selection
Committee
Antimicrobials
Division
(
7510C)

THROUGH:
Jess
Rowland
Stephen
Dapson,
Ph.
D.
Pv
Shah
Roger
Gardner
Michelle
Centra
Timothy
Leighton
Jonathan
Chen,
Ph.
D.
Deborah
Smegal
John
Redden
PC
Code:
021101,
068302,
068304
On
November
12th
,
2003,
the
Antimicrobials
Division
=

s
Toxicology
Endpoint
Selection
Committee
(
ADTC)
in
conjunction
with
the
chair
of
the
Health
Effects
Division
Hazard
Identification
Assessment
Review
Committee
(
HIARC)
met
to
discuss
risk
issues
associated
with
dermal
exposure
to
hexavalent
chromium
(
CrVI).
On
August
17,
2004,
the
ADTC
along
with
scientists
from
the
Health
Effects
Division
met
again
to
discuss
the
additional
information
and
decisions
made
regarding
dermal
exposure
to
CrVI
and
to
finalize
a
level
of
concern
for
dermal
exposure
to
this
chemical.
The
results
of
these
discussions
are
included
in
this
memorandum.
2
Committee
Members
in
Attendance
Present
at
the
meeting
were
the
following
scientists
from
the
noted
respective
divisions
within
OPP:
From
the
Health
Effects
Division:
Jess
Rowland,
Stephen
Dapson,
Pv
Shah;
from
the
Biopesticides
and
Pollution
Prevention
Division:
Roger
Gardner;
from
the
Antimicrobials
Division:
Timothy
McMahon
(
chair),
Michelle
Centra,
Timothy
Leighton,
Jonathan
Chen,
Deborah
Smegal;
from
the
Registration
Division,
John
Redden.

Data
evaluation
prepared
by:
Timothy
F.
McMahon,
Ph.
D.
3
I.
Background
On
November
12,
2003,
an
internal
workgroup
composed
of
scientists
within
the
Office
of
Pesticide
Programs
met
to
discuss
dermal
risk
issues
associated
with
exposure
to
chromium
+
6
(
CrVI)
as
present
in
Acid
Copper
Chromate
(
ACC)­
treated
wood.
Present
at
the
meeting
were
the
following
scientists
from
the
noted
respective
divisions
within
OPP:
From
the
Health
Effects
Division:
Jess
Rowland,
Stephen
Dapson,
PV
Shah,
Yung
Yang;
from
the
Biopesticides
and
Pollution
Prevention
Division:
Roger
Gardner;
from
the
Antimicrobials
Division:
Timothy
McMahon
(
chair),
Michelle
Centra,
Timothy
Leighton,
Jonathan
Chen,
Sanyvette
Williams,
Melba
Morrow,
Deborah
Smegal.

As
a
brief
background,
this
standing
workgroup
in
the
Office
of
Pesticide
Programs
deliberated
on
an
application
pending
before
the
Antimicrobials
Division
for
the
use
of
ACC­
treated
wood
as
a
replacement
for
CCA­
treated
wood.
The
Division
had
expressed
concerns
for
dermal
risks
from
exposure
to
ACC­
treated
wood,
as
there
are
potentially
higher
levels
of
CrVI
in
ACC­
treated
wood
vs.
CCA­
treated
wood
(
approximately
1.5
times
higher
CrVI
content),
and
the
A
fixation
@

time,
or
time
in
which
CrVI
is
reduced
to
the
less
toxic
chromium
+
3,
can
be
significantly
longer
for
ACC­
treated
wood.
These
factors
can
result
in
a
potential
for
residential
dermal
exposure
to
CrVI
as
well
as
the
potential
for
children
=

s
incidental
oral
exposure
from
contaminated
soil
as
the
result
of
leaching
of
ACC
from
treated
wood.

Along
with
other
issues
(
discussed
in
the
previous
memorandum),
the
committee
considered
the
following
issue
with
respect
to
CrVI
itself:

Can
an
appropriate
dermal
endpoint
for
exposure
to
chromium
+
6
be
selected
based
on
the
available
data?
What
are
the
appropriate
uncertainty
considerations
to
address
if
such
an
endpoint
is
selected?

The
results
of
the
committee
=

s
initial
deliberation
on
this
issue
was
the
following,
in
summary:

As
an
interim
working
measure,
in
November
of
2003,
the
workgroup
determined
that
the
study
of
Nethercott
(
1994)
provides
some
dose­
response
data
on
dermal
sensitization
to
CrVI.
In
this
study,
a
value
of
0.018
Fg/
cm2
(
lowest
dose
tested)
was
reported
to
elicit
a
sensitization
response.
This
value
with
an
attendant
total
uncertainty
factor
of
10x
was
selected
by
the
committee.
A
factor
of
3x
was
applied
for
selection
of
an
LOAEL
to
extrapolate
to
a
NOAEL,
and
a
factor
of
3x
was
applied
to
account
for
the
relatively
small
study
population
and
attendant
variability
therein.

The
interim
endpoint
selected
by
the
ADTC
differed
from
a
proposal
by
the
registrant
made
prior
to
the
ADTC
meeting.
In
the
registrant
=

s
proposal
(
pages
41­
42
of
the
submitted
document
A
Meeting
with
U.
S.
Environmental
Protection
Agency
Antimicrobials
Division
and
Forest
Products
Research
Laboratory,
LLC
October
30,
2003:
Documents
Submitted
to
EPA
as
of
October
30,
2003,
Volume
I
of
II)
two
values
were
suggested
as
levels
of
concern:
the
LOAEL
of
0.018
Fg/
cm2
from
the
Nethercott
et
al.
study
using
only
a
factor
of
3x
to
account
for
the
use
of
a
LOAEL,
or
the
10%
minimum
elicitation
threshold
value
of
0.088
Fg/
cm2
with
again
a
3x
uncertainty
factor.
This
results
in
two
proposed
values
of
0.006
or
0.03
Fg/
cm2.
As
stated
in
the
4
submission,
>

This
would
suggest
that
any
exposures
to
Cr(
VI)
concentration
in
treated
wood
of
less
than
0.006
Fg/
cm2
(
or
0.03
Fg/
cm2
if
using
the
minimum
elicitation
threshold)
would
be
safe...@

II.
Update
of
Hexavalent
Chromium
Dermal
Risk
Issue
Following
the
selection
of
the
level
of
concern
for
hexavalent
chromium
by
the
ADTC,
scientific
issues
related
to
the
use
of
a
quantitative
RfD
approach
for
assessment
of
dermal
sensitization
risk
were
raised
by
the
registrant
of
the
treated
wood
product.
It
was
recognized
that
within
the
Agency,
quantitation
of
such
risk
had
never
been
performed
although
the
issue
had
been
raised
within
the
Office
of
Pesticide
Programs
with
regard
to
certain
agricultural
pesticides.
Thus,
the
issue
was
presented
before
the
FIFRA
Scientific
Advisory
Panel
(
SAP)
as
part
of
a
set
of
issues
on
May
4­
6,
2004.
The
SAP
issued
their
final
report
in
July
of
2004.

With
respect
to
the
question
of
sensitization
potential
from
exposure
to
hexavalent
chromium
in
treated
wood
and
what
level
of
concern
should
be
established,
the
SAP
recognized
that
allergic
contact
dermatitis
from
exposure
to
CrVI
may
sometimes
be
very
severe
with
a
major
impact
on
the
quality
of
life
for
some
sensitized
individuals.
The
condition
can
be
reversed
when
exposure
is
removed.
There
is
currently
no
published
literature
to
suggest
that
allergic
contact
dermatitis
results
from
exposure
to
chromate
in
treated
wood
(
although
no
such
studies
have
been
conducted
specifically,
and
no
such
data
exist
for
the
treated
wood
product
registration
currently
before
the
Agency­
comment
added).

Considering
all
of
the
data
made
available,
the
SAP
identified
the
same
study
as
that
chosen
by
the
ADTC
(
Nethercott
et
al.,
1994)
as
the
best
available
regarding
quantitation
of
a
level
of
CrVI
causing
dermal
sensitization
using
a
sensitized
human
study
population.
The
Panel
identified
the
A
critical
dose
(
lowest
observed
adverse
effect
level
[
LOAEL])
from
the
Nethercott
et
al.
(
1994)
study
should
be
0.088
Fg/
cm2,
which
the
Panel
considered
to
be
a
conservative
safety
level.@
This
represented
the
10%
minumum
elicitation
threshold,
or
MET,
in
that
study.

Uncertainty
considerations
in
the
selection
of
the
endpoint
included
inter­
and
intra­
species
variability,
and
exposure
matrix
uncertainty
(
i.
e.
differences
between
the
exposures
in
the
critical
study
which
was
an
acute
exposure
with
the
treated
area
occluded
and
anticipated
product
exposures,
which
are
expected
to
be
repeated
and
not
involve
occlusion).

As
a
result
of
the
Panel
=

s
recommendation,
the
estimated
RfD
was
determined
to
encompass
a
range
of
0.09­
0.3
Fg/
cm2
based
on
the
use
of
the
following
factors,
as
taken
from
the
SAP
report:

Condition
SAP
Recommended
Uncertainty
Factor
Matrix/
vehicle
factor
0.1
Interspecies
variation
(
uncertainty)
1
Intraspecies
variation
(
uncertainty)
1
Exposure
factor
3­
10
5
The
actual
calculation
is
illustrated,
from
the
SAP
report:

S­
RfD
=
0.088
Fg/
cm2
=
0.09
­
0.3
Fg/
cm2
(
1)(
1)(
0.1)(
3
to10)

The
Panel
concluded
that
this
estimate
of
a
RfD
should
be
protective
against
elicitation
(
i.
e.
reactions
in
already
sensitized
persons)
and
therefore
would
also
be
protective
against
induction
(
i.
e.
reaction
in
non­
sensitized
persons).
However,
the
Panel
also
stressed
that
the
Agency
A
consider
all
data
as
part
of
a
weight
of
evidence
approach.@

Subsequent
Agency
Considerations
The
Agency
recognized
that
defining
a
RfD
for
dermal
sensitization
was
a
new
approach.
Moreover,
there
was
a
need
to
better
characterize
uncertainty
to
account
for
differences
in
exposure
between
the
critical
study
and
the
anticipated
exposures.
These
issues
were
presented
to
the
Agency
=

s
Science
Policy
Council
Steering
Committee
(
SPC
SC)
on
August
11,
2004
for
further
discussion.

The
SPC
SC
considered
these
two
areas
and
provided
comments:
The
SPC
SC
agreed
that
dermal
sensitization
can
be
used
in
an
approach
to
determine
a
RfD.
Secondly,
the
UFs
for
matrix/
vehicle
and
exposure
as
recommended
by
the
SAP
are
not
recognized
UFs
by
the
Agency
(
cf.,
Agency
RfD/
RfC
technical
report
document,
EPA/
630/
P­
02/
002F,
2002).
Further,
factors
of
less
than
1
are
typically
not
applied.
The
SPC
SC
stated
that,
as
a
policy
issue,
it
does
not
recommend
setting
UFs
of
less
than
1
without
actual
data
to
indicate
it
is
appropriate
to
do
so
(
there
are
no
data
on
these
issues
for
Cr(
VI)).

In
this
particular
instance,
the
SPC
SC
recommended
that
to
address
the
SAP's
concerns
about
occlusion
and
repeated
exposure
are
to
be
addressed,
they
should
be
characterized
as
dose
adjustment
factors
to
apply
to
this
particular
situation
of
exposure
to
hexavalent
chromium
in
treated
wood
and
not
as
a
general
policy
at
this
time.
Dose
adjustment
can
be
thought
of
in
terms
of
what
concentration
of
chemical
would
cause
a
sensitization
response
under
occluded
vs.
nonoccluded
conditions,
and
how
repeated
exposures
over
time
might
cause
sensitization
reactions
in
the
human
population,
given
the
inherent
variability
of
the
human
population.
It
has
been
suggested
that,
given
the
same
area
dose
to
the
skin,
occluded
conditions
would
lead
to
a
sensitization
reaction
that
might
not
otherwise
occur
under
non­
occluded
conditions.
However,
this
statement,
particularly
with
regard
to
hexavalent
chromium,
has
never
been
systematically
investigated.
Thus
there
are
no
data
to
suggest
what
the
actual
magnitude
of
this
factor
would
be;
it
is
likely
a
chemical­
specific
phenomenon
and
could
vary
,
based
on
the
potency
of
the
sensitizing
agent.
The
SPC
SC
noted
that
further
study
is
necessary
to
examine
the
comparative
dose
between
occluded
and
non­
occluded
exposures
to
hexavalent
chromium
exposure.
6
The
use
of
a
factor
to
account
for
repeated
exposures
an
individual
may
receive
from
contacting
ACC­
treated
wood
was
supported
by
the
SPC
SC,
but
the
factor
was
felt
to
be
more
indicative
in
this
case
as
one
to
account
for
variations
in
response
to
repeated
exposure
among
the
human
population
(
i.
e.,
intraspecies
variation
UF)
.
Even
among
sensitized
individuals,
variations
in
response
may
occur
due
to
age,
gender,
previous
history
of
sensitization,
skin
condition,
etc.
and
the
response
over
time
to
repeated
exposures
may
also
show
variability.
There
was
no
specific
recommendation
of
the
SPC
SC
regarding
the
magnitude
of
this
factor.

Based
on
the
discussions
with
the
SPC
SC,
the
ADTC
was
convened
again
on
August
17,
2004
to
consider
all
of
the
updated
information
and
peer
reviews
since
issuance
of
the
first
memorandum
of
November
2003
and
to
decide
on
a
level
of
concern
regarding
the
concentration
of
hexavalent
chromium
on
the
surface
of
ACC­
treated
wood
that
would
be
protective
against
development
of
ACD.

Conclusions
of
Second
ADTC
Meeting
The
ADTC,
in
light
of
all
the
information
made
available
since
addressing
the
issue
of
dermal
sensitization
and
risk
assessment
(
including
open
literature,
the
SAP
recommendations,
and
the
SPC
SC
comments),
concluded
the
following:

1)
The
ADTC
agreed
with
the
SAP
recommendation
of
the
use
of
the
10%
MET
value
of
0.088
Fg/
cm2
from
the
Nethercott
et
al.
(
1994)
study
instead
of
the
previously
selected
value
of
0.018
Fg/
cm2
from
that
same
study.

2)
The
ADTC
agreed
with
the
SPC
=

s
SC
comment
that
a
dose
adjustment
factor
of
0.1
for
matrix
effects
was
not
supported
and
would
not
be
applied
at
this
time
for
determination
of
a
level
of
concern
for
hexavalent
chromium.
More
data
to
address
this
specific
issue
are
necessary
as
noted
above.

3)
The
ADTC
concluded
that,
for
addressing
the
human
variability
regarding
sensitization
from
repeated
dermal
exposures
expected
with
ACC­
treated
wood,
a
factor
of
10x
is
appropriate
at
this
time.
A
different
factor
is
not
warranted
at
this
time,
as
(
a)
there
is
no
definitive
data
on
levels
of
hexavalent
chromium
on
the
surface
of
freshly­
treated
wood
using
the
ACC
treatment
solution,
nor
is
there
definitive
data
on
the
time
course
for
the
conversion
of
this
surface
level
to
chromium
III
(
Cr
III);
and
(
b)
there
is
expected
to
be
variation
in
the
response
to
repeated
exposures
to
surface
residues
of
hexavalent
chromium
in
humans
but
there
is
no
data
to
suggest
a
different
factor.
As
data
become
available
regarding
human
variability
and
levels
of
Cr(
VI)
on
wood,
the
ADTC
can
revisit
the
RfD
for
Cr(
VI)
treated
wood.
7
Recommendation/
Conclusion:

The
derivation
of
the
level
of
concern
by
the
ADTC
for
hexavalent
chromium,
based
on
peer
review
by
the
FIFRA
SAP
and
comment
from
the
Agency
=

s
SPC
SC,
is
summarized
below.
At
this
time,
it
is
concluded
that
an
UF
that
applies
here
is
a
factor
of
10
for
intraspecies
variation.
This
factor
is
applied
at
this
time
based
on
the
lack
of
definitive
data
on
levels
of
hexavalent
chromium
on
the
surface
of
freshly­
treated
wood
using
the
ACC
treatment
solution,
the
lack
of
definitive
data
on
the
time
course
for
the
conversion
of
the
surface
level
to
chromium
III
(
Cr
III),
and
the
lack
of
definitive
data
on
variation
in
the
response
to
repeated
exposures
to
surface
residues
of
hexavalent
chromium
in
humans.
As
more
data
become
available,
the
10x
factor
can
be
reconsidered.

The
derivation
of
the
sensitization
RfD,
based
on
this
conclusion,
is
thus:

S­
RfD
=
0.088
Fg/
cm2
=
0.009
Fg/
cm2
(
10)

.
