[Federal Register Volume 80, Number 28 (Wednesday, February 11, 2015)]
[Notices]
[Pages 7674-7675]
[FR Doc No: 2015-02785]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

[Summary Notice No. PE-2015-02 ]

Petition for Exemption; Summary of Petition Received

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of petition for exemption received.

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SUMMARY: This notice contains a summary of a petition seeking relief
from specified requirements of 14 CFR. The purpose of this notice is to
improve the public's awareness of, and participation in, this aspect of
FAA's regulatory activities. Neither publication of this notice nor the
inclusion or omission of information in the summary is intended to
affect the legal status of the petition or its final disposition.

DATES: Comments on this petition must identify the petition docket
number and must be received on or before February 23, 2015.

ADDRESSES: You may send comments identified by Docket Number FAA-2014-
0482 using any of the following methods:
     Government-wide rulemaking Web site: Go to http://www.regulations.gov and follow the instructions for sending your
comments electronically.
     Mail: Send comments to the Docket Management Facility;
U.S. Department of Transportation, 1200 New Jersey Avenue SE., West
Building Ground Floor, Room W12-140, Washington, DC 20590.
     Fax: Fax comments to the Docket Management Facility at
202-493-2251.
     Hand Delivery: Bring comments to the Docket Management
Facility in Room W12-140 of the West Building Ground Floor at 1200 New
Jersey Avenue SE., Washington, DC, between 9 a.m. and 5 p.m., Monday
through Friday, except Federal holidays.
    Privacy: We will post all comments we receive, without change, to
http://www.regulations.gov, including any personal information you
provide. Using the search function of our docket Web site, anyone can
find and read the comments received into any of our dockets, including
the name of the individual sending the comment (or signing the comment
for an association, business, labor union, etc.). You may review DOT's
complete Privacy Act Statement in the Federal Register published on
April 11, 2000 (65 FR 19477-78).
    Docket: To read background documents or comments received, go to
http://www.regulations.gov at any time or to the Docket Management
Facility in Room W12-140 of the West Building Ground Floor at 1200 New
Jersey Avenue SE., Washington, DC, between 9 a.m. and 5 p.m., Monday
through Friday, except Federal holidays.

FOR FURTHER INFORMATION CONTACT: Sandra K. Long, ARM-201, Office of
Rulemaking, 800 Independence Ave SW., Washington DC 20591, 202-267-
7414, Sandra.long@faa-gov
    This notice is published pursuant to 14 CFR 11.85.

    Issued in Washington, DC, on February 5, 2015.
Lirio Liu,
Director, Office of Rulemaking.

Petition for Exemption

    Docket Nos.: FAA-2014-0482, FAA-2014-0992, FAA-2014-0993.
    Petitioner: Commemorative Air Force.
    Section of 14 CFR Affected: 14 CFR 91.319(c).

    Description of Relief Sought: The petitioner is seeking relief to
allow it to operate multiple single and multi-engine experimental
aircraft over densely populated areas during the celebration of the
70th Anniversary of the WWII Victory in Europe Day on May 8, 2015.

[FR Doc. 2015-02785 Filed 2-10-15; 8:45 am]
BILLING CODE 4910-13-P


For #86 (Data CD with DDVP DEEM R98 and RDF Files):

"This CD-ROM contains 64 residue distribution (*.rdf) files and 2 *.R98
files.  The *.rdf files are text files that contain residue
distributions for many of the foods included in the DDVP assessment.
Each of these files may contain summary source information as a header.
The .R98 files are the input files necessary for estimating the food
exposure using DEEM-FCID.  The *.R98 files contain all of the
appropriate input parameters, including either residue values or
pointers to residue distribution files (*.rdf files described above),
for acute and chronic analyses.  The CD-ROM containing all of these
files is located in the DDVP Special Review Docket
(EPA-HQ-OPP-2006-0396)."


	UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

DATE: December 21, 2006

MEMORANDUM

SUBJECT:	Hexavalent Chromium – Summary of issues related to
Quantitation of Dermal Sensitization Risk from exposure to treated wood
containing hexavalent chromium

FROM:	Timothy F. McMahon, Ph.D.

		Senior Toxicologist

Antimicrobials  Division (7510C)

THROUGH:   Timothy Leighton

Jonathan Chen, Ph.D.

John Liccione

PC Codes: 021101, 068302, 068304

This memorandum presents summary results of several meetings that have
occurred between 2003 and the present date involving The Office of
Pesticide Program’s efforts to form a scientifically sound basis for
quantitation of dermal sensitization risk, using hexavalent chromium as
a case study and application of this methodology to assessment of risk
to wood preservatives containing hexavalent chromium to which repeated
dermal contact could occur.

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) and to make an initial
recommendation of a level of concern for dermal exposure to CrVI.  In
July of 2004, a set of scientific issues was presented to the FIFRA
Scientific Advisory Panel to further the development of a quantitative
approach to assessment of dermal sensitization risk. On August 17, 2004,
the ADTC along with scientists from the Health Effects Division met
again to discuss  additional information and recommendations made by the
FIFRA Science Advisory Panel and the EPA’s Science Policy Council
Steering Committee  regarding dermal exposure to CrVI and to reconsider
the level of concern for dermal exposure to this chemical.  In addition,
the study of Nethercott et al. on which the level of concern for CrVI
was based was presented before the Agency’s Human Studies Review Board
(HSRB) in May of 2006 for  their comment on the scientific and ethical
merits of this study.  In July of 2006, a Repeat Open Application Test
(ROAT) study was submitted to the Office of Pesticide Programs for the
purpose of refining further the level of concern recommended by the
FIFRA SAP.  On October 17-18, 2006,  a meeting was held with the
Agency’s Human Studies Review Board to consider  scientific and
ethical issues with regard to the ROAT  that was submitted.

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 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 “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.

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 µg/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 “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:   (a) the LOAEL of 0.018  µg/cm2 from the
Nethercott et al.  study using only a 3x uncertainty  factor  to account
for the use of a LOAEL;  or (b) the 10% minimum elicitation threshold
value of 0.088 µg/cm2  also using  a 3x uncertainty factor.  This
results in two proposed values of 0.006 or 0.03 µg/cm2 as levels of
concern for repeated dermal contact with CrVI.   As stated in the
submission, ‘This would suggest that any exposures to Cr(VI)
concentration in treated wood of less than 0.006 µg/cm2 (or 0.03
µg/cm2 if using the minimum elicitation threshold) would be safe...”

II. Update of Hexavalent Chromium Dermal Risk Issue

Following the selection of  an initial level of concern for dermal
exposure to 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 applicant seeking registration of
the treated wood product.  It was recognized that within the Agency, a
quantitative approach to assessment of dermal sensitization risk  had
never been performed,  although the issue had been raised within the
Office of Pesticide Programs with regard to certain agricultural
pesticides.  In order to form a scientifically sound basis for using a
quantitative approach to assessment  of dermal sensitization, the Office
of Pesticide Programs presented a set of issues to the  FIFRA Scientific
Advisory Panel (SAP)  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 available
published literature to suggest that allergic contact dermatitis results
from exposure to chromate in treated wood

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 in
their report stated that the “critical dose (lowest observed adverse
effect level [LOAEL]) from the Nethercott et al. (1994) study should be
0.088 µg/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 µg/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

The actual calculation of the ‘sensitization Reference Dose’ (S-RfD)
is illustrated, from the SAP report:

 S-RfD =          0.088 µg/cm2   =   0.09 - 0.3 µg/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 “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,
uncertainty factors of less than 1 are typically not applied by the
Agency. 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 were no data on these issues for Cr(VI) at
the time).

  In this particular instance, the SPC SC recommended that to address
the SAP's concerns about occlusion and repeated exposure, 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. non-occluded 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.  There were no data at the time 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.

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.

III. 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 µg/cm2 from the Nethercott et al. (1994) study instead
of the previously selected value of 0.018 µg/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 are 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.

 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.    It was concluded at that time
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 derived value for a sensitization RfD  based on all discussions held
and materials considered up to August of 2004  was as follows:

S-RfD =          0.088 µg/cm2   =   0.009  µg/cm2

           (10)

In May of 2006, the study of Nethercott et al. upon which the derivation
of the S-RfD was based was presented to the Agency’s Human Studies
Review Board for their comment on the scientific and ethical merits of
this study.  At this time the concept of the Minimum Elicitation
Threshold, or MET, replaced the S-RfD terminology.

IV. Developments Since August 2004

As part of the SAP report in 2004, the Panel suggested a Repeat Open
Application Test (ROAT) study could be conducted to better represent
real-life exposures to treated wood containing hexavalent chromium for
refinement of this risk assessment.  Although not specifically requested
by the Agency, the registrant did conduct such a study and this study
was submitted and reviewed by the Office of Pesticide Programs’
Antimicrobials Division in 2006. The executive summary of this study is
presented below.

CITATIONS:

Proctor, D.; Gujral, S.; Fowler, J. (2006) Repeated Open Application
Test for Allergic Contact Dermatitis due to Hexavalent Chromium [Cr(VI)]
as CopperShield®: Risk Assessment for Dermal Contact with Cr(VI).
Unpublished study conducted by Dermatology Specialists, PSC, and
Exponent under Project No. FPRL #012506. 324 p. (MRID 46884001)

Proctor, D.; Gujral, S.; Fowler, J. (2006) Supplemental Information to
the Final Report Titled “Repeated Open Application Test for Allergic
Contact Dermatitis due to Hexavalent Chromium [Cr(VI)] as
CopperShield®: Risk Assessment for Dermal Contact with Cr(VI).”
Unpublished document dated August 24, 2006. Project No. FPRL #012506.
347 p. (MRID 46922901)

Proctor, D.; Gujral, S.; Su, S.; Fowler, J. (2006) Repeated Open
Application Test for Allergic Contact Dermatitis due to Hexavalent
Chromium [Cr(VI)] as Potassium Dichromate: Risk Assessment for Dermal
Contact with Cr(VI). Unpublished study conducted by Dermatology
Specialists, PSC, and Exponent under Project No. FPRL #012406. Includes
Supplemental Information documenting ethical conduct of the research.
664 p. (MRID 46930701)

EXECUTIVE SUMMARY:

A Repeat Open Application Test (ROAT) was performed on 60
chrome-sensitive human subjects and 10 non-sensitive control subjects.
Sensitization status of subjects was confirmed through occluded patch
testing.  The purpose of this study was to develop a 10% minimum
elicitation threshold value (MET10%) for elicitation of allergic contact
dermatitis for hexavalent chromium (as contained within the
CopperShield® wood preservative treatment solution).  The study design
involved the application of five concentrations of hexavalent chromium
(as contained within the CopperShield® wood preservative treatment
solution) to the right forearm of the test subjects and application of
five concentrations of potassium dichromate to the left forearm of the
same subjects. Ten additional subjects not sensitive to hexavalent
chromium served as controls using the highest concentration of copper
contained within the wood treatment solution.

Test subjects received application of both CopperShield® treatment
solution and potassium dichromate once per day for 10 days.   After a
6-hour exposure the subjects washed their forearms using soap provided
to them.  Prior to the next application, participants were evaluated for
occurrence of any skin responses, including erythema, papules, pruritis,
scaling, and vesicles.  Results were evaluated by Dr. Fowler, who
interpreted them as either allergic or irritant in nature and graded
each response.  Seventy-two hours following the last testing day
participants were evaluated by Dr. Fowler to determine if an allergic
contact dermatitis response had occurred.   Results from the ROAT phase
of the study were modeled using Benchmark Dose Software (BMDS) to fit
the dose-response data and calculate the 10% Minimum Elicitation
Threshold value.

Results of closed-patch testing with potassium dichromate using 12mm
Finn Chambers showed that all participants for the ROAT phase of the
study were confirmed to have sensitivity to hexavalent chromium.
According to the report, the proportion of participants in the ROAT
phase of the study who exhibited a high grade of ACD response (+3) in
this patch test was much higher than than the overall proportion graded
at +3 in the North American Contact Dermatitis Group database from
1998-2002.  Twenty-six percent (26%) of the ROAT study participants
showed a +3 reaction to the initial patch test, while the NACDG database
of 495 individuals shows a 7.7% response percentage for a +3 reaction.
Thus, in an effort to make the dose-response observed in this study more
representative of the overall hexavalent chromium-sensitized population
in the United States, the authors reported both unadjusted results and
results adjusted to the NACDG database by simulating the percent
response expected in the ROAT study if the proportions of +1, +2, and +3
responders in the current study had been consistent with those in the
NACDG database.

In addition to this adjustment of the dose-response data, two scenarios
were modeled from the CopperShield® results.  Scenario 1 included only
responses graded as allergic in nature.  Scenario 2 combined both
irritant and allergic responses in calculation of a 10% response level.

For Scenarios 1 and 2, the report stated that of all the models run, the
unconstrained log-probit model provided the best fit for the
dose-response data.   For CopperShield®, the 10% MET values for
Scenarios 1 and 2 of the unadjusted dose-response data were 270 and 91.8
ng Cr(VI)/cm2 respectively, while 10% MET values for the adjusted data
were 349 and 166 ng Cr(VI)/cm2 respectively.   With the exception of the
Scenario 2 unadjusted data, these 10% MET values are higher than the
value by Nethercott et al. (1994) of 89 ng Cr(VI)/cm2 from occluded
patch testing.

This study is classified acceptable/non-guideline and fulfills the
purpose for which it was conducted.

Because this study involved intentional exposure of human subjects and
reported a toxic endpoint, EPA’s rule for the protection of human
subjects of research requires review of the study by the Human Studies
Review Board (HSRB).  The ROAT study was presented to the HSRB on
October 18, 2006 for their advice on its scientific and ethical merits.

The HSRB considered the ROAT study to be scientifically sound and
ethically acceptable.  The HSRB recommended defining the level of
concern (10% MET) based on Scenario 2 data, combining allergic and
irritant responses, without adjustment to the NACDG database.   The HSRB
recommended use of Scenario 2 data because:

The principal investigator, Dr. Fowler, was not blinded to the dose
levels on the test subjects

Only one person made the observations of ACD vs irritation when two
would have been more appropriate

The control group of non sensitized individuals that received the ACC
solution did not exhibit irritation (nor ACD).

In addition, the HSRB recommended that the non-normalized data set be
used on the basis that the dose level used in the patch test portion of
the ROAT study compared to the dose level for the individuals in the
NACDG data base is unknown, and that  there is uncertainty in comparing
the data in the older NACDG data base and the data from the ROAT study
(e.g., potential changes in the population’s chromium sensitivity over
time and how  ROAT study test subjects would fit into the NACDG
database).

The value recommended by the HSRB and selected by the Agency is 91.8 ng
Cr(VI)/cm2 (rounded to 92 ng Cr(VI)/cm2).  This value is similar to the
previously reported 10% MET value of 89 ng Cr(VI)/cm2 derived from the
1994 study of Nethercott et al., recommended by the SAP and adopted by
the Agency in 2004.

In the memorandum of August 30, 2004, a 10x uncertainty factor was
applied to the 10% MET value of 0.088 µg/cm2  selected from the
Nethercott et al. study, resulting in a level of concern of 0.009
µg/cm2  for CrVI residues on ACC-treated wood.  The 10x uncertainty
factor was applied for three reasons:

There was no definitive data on levels of hexavalent chromium on the
surface of freshly-treated wood using the ACC treatment solution

There was no definitive data on the time course for the conversion of
surface residues of Cr VI to chromium III (Cr III)

There is expected to be variation in the response to repeated exposures
to surface residues of Cr VI in humans.

Since 2004 data on surface residues of CrVI on freshly treated wood
using the ACC treatment solution and on the time-course of conversion
from CrVI to CrIII have become available.  In addition, the ROAT study
has provided data on elicitation thresholds following repeated open
application.  These new data address the initial uncertainties that were
expressed by the Agency in 2004 and support removal of the 10x
uncertainty factor and the use of the 92 ng Cr(VI)/cm2 value for
regulatory purposes.

A comment from Elizabeth Brown, Ph.D., of Steptoe and Johnson, LLP, to
the HSRB argued for retaining a 10x uncertainty factor, and raised
several issues, summarized below, with the Agency’s response:

Issue 1: Both children and adults are likely to contact residues on
treated wood multiple times daily.  The single daily exposure in the
ROAT study may not be representative of the actual exposure.  In
addition, oral exposure of children from hand-to-mouth behavior may
increase potential for sensitization.

Agency Response:

It is understood that there may be more than a single daily contact with
treated wood.  However, the exposure in the ROAT study was for a 6 hour
duration and involved subjects with known sensitivity to Cr(VI).  This
exposure was carried out over a period of 10 days and is considered a
conservative model for dermal sensitization exposure to Cr(VI) in
treated wood for residential risk assessment purposes.  As for the
potential of oral exposure to result in dermal sensitization, there are
very few reports of this in the scientific literature, and these are
limited to a few individuals.  As suggested by Farage et al. (Contact
Dermatitis 49(3): 140-147), the use of larger uncertainty factors to
account for contact sensitization from mucosal (oral) exposures is
likely based upon the increased permeability of mucosal surfaces as
compared to the skin and not an inherent increased susceptibility by the
oral route.  In addition, any oral risk assessment would be conducted
using an endpoint based on an oral study, not a dermal study.

Issue 2:  Consumers can come in to contact with Cr(VI) from multiple
sources, as well as from Cr(III).  The potential for additive exposure
needs to be taken into consideration.

Agency Response:

In addition to the known sensitivity to Cr(VI) in the study subjects, it
was also known that these subjects had been previously exposed to
chromium from many sources.  Thus, having a study population that
already includes exposures from several sources is inclusive of any
increased potential sensitivity.  With regard to exposure to Cr(III),
the available scientific literature on thresholds for dermal
sensitization show clearly that induction  and sensitization thresholds
are much higher for Cr(III) than Cr(VI).

Issue 3:  Damaged skin can further increase the likelihood of an adverse
response (e.g., ACD) in addition to the normal human variability in
response to sensitizers.  Eczema is a predisposing condition for
allergic contact dermatitis.

Agency Response:

The chromium-sensitive population selected in the Proctor et al. 2006
study likely had particular sensitivity to Cr(VI), supported by the
observation (and as noted by the HSRB) that the control subjects in the
Proctor et al. study showed no irritant responses to Cr(VI).  Thus,
basing the 10% MET value on this study population includes not only
persons with known Cr(VI) sensitivity, but likely includes the prior
history of irritancy and effects of compromised skin. Uncertainty is
possible.     From a practical standpoint, the 10% MET, which is already
known to be protective of 99% of the general population (as noted in
Nethercott et al., 1994) is felt to be protective in this case.

Issue 4:  The use of a LOAEL strongly suggests that a UF of 10x should
be applied to adequately protect consumers who contact wood treated with
the ACC treatment solution.

Agency Response:

The quantitative assessment for dermal sensitization is based not on a
LOAEL but on the MET10. The MET is defined by a specific response level;
in the present case, the 10% response level was determined by the FIFRA
SAP to be adequate and sufficiently conservative. The LOAEL by contrast
does not imply a specific level of response but an interpretation of an
adverse effect at a certain dose level.  An uncertainty factor does not
necessarily need to be applied to the MET as it is traditionally done in
the case of the use of a LOAEL, as the MET is more analogous to a
benchmark dose, to which uncertainty factors are not routinely applied.

Conclusions

The 10x uncertainty factor that was applied to the 10% MET value
selected from the single occluded dose Nethercott study in 2004 is no
longer needed.  The value of  92 ng Cr(VI)/cm2 as recommended by the
HSRB is a  level of dermal exposure at which elicitation of allergic
contact dermatitis is not expected to occur from repeated dermal contact
with ACC-treated wood, and can be used for the dermal risk assessment of
CrVI in ACC-treated wood as the updated 10% MET.

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