UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

		     WASHINGTON, D.C. 20460

							                                              OFFICE OF

				PREVENTION, PESTICIDES

	AND TOXIC SUBSTANCES

March 24, 2008

MEMORANDUM

SUBJECT:	Response to Comments on the Preliminary Risk Assessments for
Wood

Preservatives Containing Arsenic and/or Chromium

FROM:	Lance Wormell, Chemical Review Manager

		A. Najm Shamim, PhD., Chemist

		Regulatory Management Branch 2

Antimicrobials Division (7510P)

Nader Elkassabany, Team Leader

Jonathan Chen, Ph.D., Risk Assessor

Tim McMahon, Ph.D., Toxicologist

Doreen Aviado, Occupational Risk Assessor

Rick Petrie, Ecological Risk Assessor

Siroos Mostaghimi, Environmental Modeler

Risk Assessment and Science Support Branch

Antimicrobials Division (7510P)

THROUGH:	Mark Hartman, Chief

		Regulatory Management Branch 2

Antimicrobials Division (7510P)

Norm Cook, Chief

Risk Assessment and Science Support Branch

Antimicrobials Division (7510P)

TO:		Public Docket EPA-HQ-OPP-2003-0250

	This document presents the Environmental Protection Agency’s (EPA or
“the Agency”) formal response to the comments received on the 2004
preliminary risk assessments for CCA heavy duty wood preservative uses.
These comments were received during the 60-day public comment period
that ended on May 17, 2004.

	During the comment periods EPA received comments from approximately 35
stakeholders (see Table 1).  EPA’s responses to these comments are
presented by topic in nine sections: Chemical Overview, Residue
Chemistry, Hazard, Human Exposure, Worker Study Review, Occupational
Risk, Environmental Risk, Benefits and Alternatives, and Risk
Mitigation.

Table 1. Docket IDs by Respondent Name

Docket ID	Respondent Name

EPA-HQ-OPP-2003-0250-0014	Citizen

EPA-HQ-OPP-2003-0250-0015	Citizen

EPA-HQ-OPP-2003-0250-0016	No comment or respondent associated with this
entry

EPA-HQ-OPP-2003-0250-0017	Evercrete Corp.

EPA-HQ-OPP-2003-0250-0018	California Regional Water Quality Control
Board

EPA-HQ-OPP-2003-0250-0019	Vetter Building Supply

EPA-HQ-OPP-2003-0250-0020	Citizen

EPA-HQ-OPP-2003-0250-0021	Steel and Post Building Supply

EPA-HQ-OPP-2003-0250-0022	Citizen

EPA-HQ-OPP-2003-0250-0023	A.J. Manufacturing, Inc.

EPA-HQ-OPP-2003-0250-0024	Citizen

EPA-HQ-OPP-2003-0250-0025	Hos-Cot Builders

EPA-HQ-OPP-2003-0250-0026	Thomsen Construction and Supply Co.

EPA-HQ-OPP-2003-0250-0027	Lester Building Systems

EPA-HQ-OPP-2003-0250-0028	Citizen

EPA-HQ-OPP-2003-0250-0029	Citizen

EPA-HQ-OPP-2003-0250-0030	Wick Buildings

EPA-HQ-OPP-2003-0250-0031	Rutgers University

EPA-HQ-OPP-2003-0250-0032	Blitz Builders

EPA-HQ-OPP-2003-0250-0033	No comment or respondent associated with this
entry

EPA-HQ-OPP-2003-0250-0034	San Francisco Dept. of the Environment

EPA-HQ-OPP-2003-0250-0035	Wood Truss Council

EPA-HQ-OPP-2003-0250-0036	Morton Buildings

EPA-HQ-OPP-2003-0250-0037	BANCCA.ORG

EPA-HQ-OPP-2003-0250-0038	Tailored Building Systems

EPA-HQ-OPP-2003-0250-0039	US Fish and Wildlife Service

EPA-HQ-OPP-2003-0250-0040	Competitive Enterprise Institute

EPA-HQ-OPP-2003-0250-0041	J.H. Baxter and Co.

EPA-HQ-OPP-2003-0250-0042	American Chemistry Council

EPA-HQ-OPP-2003-0250-0043	Gradient (for the American Chemistry Council)

EPA-HQ-OPP-2003-0250-0044	USWAG

EPA-HQ-OPP-2003-0250-0045	Sturdi-Built Corp.

EPA-HQ-OPP-2003-0250-0046	Hoge Lumber Co.

EPA-HQ-OPP-2003-0250-0047	Little Construction Co.

EPA-HQ-OPP-2003-0250-0048	Citizen

Chemical Overview Comments and Responses

Comment: The Chemical Overview section presents incorrect information on
products, use profile, target pests, application rates, RPAR, and the
Consumer Awareness Program.

EPA Response: The most recent and accurate information on products, use
profile, target pests, application rates, RPAR, and the Consumer
Awareness Program is presented in the revised Chemical Overview chapter.

Comment: EPA appears to allege that certain data requirements have not
been fulfilled but does not present information on any unfulfilled data
requirements.

EPA Response: Unfulfilled data requirements and/or future data needs
will be presented in the revised Chemical Overview chapter and/or the
reregistration eligibility decision (RED).

Residue Chemistry Comment and Response

Comment: The Residue Chemistry chapter focuses on a use that has been
deleted (home gardens) and contains inaccurate information.

EPA Response:  Because the use profile for CCA no longer includes uses
that will result in food exposure, a residue chemistry chapter is not
required.  The risk assessment will updated to reflect this change.

Hazard Comments and Responses

Comment: EPA should consider new scientific data that have become
available since the 2001 SAP reviewed several relevant issues regarding
the health effects of inorganic arsenic.

EPA Response:  The final CCA risk assessments will be based on the most
up-to-date information.  In 2004, the Agency presented issues associated
with both organic and inorganic arsenic hazard assessments to the
Scientific Advisory Board (SAB) and its final report was released in
2007.  The Agency is evaluating the impact of the new scientific
information and the SAB report on both cancer and non-cancer effects
associated with the inorganic arsenic exposure.

Comment: Inorganic chromium hazards and risk analysis failed to consider
the distinctions between the oral animal studies and the exposure to CCA
residues.

EPA Response:  The final CCA risk assessments will be based on the most
up-to-date information including both animal and human studies.

Comment: The majority of the chromium from wood treating is trivalent
not hexavalent.

EPA Response:  EPA agrees that most of the Cr(VI) will be converted to
Cr(III) after fixation; however, the risk assessment focuses on exposure
to Cr(VI) because it is many times more toxicologically potent than
Cr(III).

Comment: EPA did not consider important factors in deriving the human
hazard for chromium from the animal studies.

EPA Response:  The final CCA risk assessments will be based on the most
up-to-date information including consideration of all relevant factors
in deriving the human hazard for chromium from the animal studies.

Comment: There are concerns regarding the inhalation study relied upon
by EPA.

EPA Response:  The Agency will incorporate the comments on the
inhalation study in its final risk assessment.

Comment: EPA must consider the differences in exposure in wood treating
plants and chrome plating plants.

EPA Response:  In the risk assessment, both hazard identification and
exposure assessment are important.  For hazard assessment, because
Cr(VI) is the primary concern, any hazard associated with Cr(VI) will be
considered, no matter where the exposure is happening.  For the exposure
assessment, it is important to use  risk assessment specific exposure
information.  This is the reason, it is important for wood treatment
related risk assessment Agency will use the wood treatment plant
specific information.  For hazard assessment, however, the Agency will
consider all available information associated with Cr(VI) exposure.

Comment: OPP should revise the toxicity benchmark that it uses to
estimate short- and intermediate-term risk estimates to better reflect
available scientific data, including recently published studies
examining the noncancer toxicity of arsenic intake in therapeutic and
other settings.

EPA Response:  The final CCA risk assessment will consider all available
studies.

Comment: OPP should revise the toxicity benchmark that it uses to
estimate long-term risk estimates to better reflect available scientific
data, including recently published data regarding the impact of
malnutrition in enhancing susceptibility to arsenic-related health
effects.

EPA Response:  Malnutrition is a potential uncertainty associated with
the susceptibility to arsenic-related health effects, however, more
recent scientific evidence suggests that the toxicity associated with
inorganic arsenic exposure may involves several potential modes of
action.  In addition, inorganic arsenic exposure may be associated with
a wide range of health concerns, including neurotoxicity, cardiac
effects, diabetic concerns, etc.  Many of the effects are not
necessarily associated with malnutrition.

Comment: The assumption used to quantify dermal absorption of arsenic is
overly conservative and does not adequately reflect currently available
scientific information, including new absorption data from a recently
conducted animal study and relevant exposure data for the studied worker
population.

EPA Response:  The Agency is aware of the potential conservatism
associated with the dermal absorption of inorganic arsenic.  In the 2001
SAP meeting, the Panel cited the research of Wester et al. (1993) as a
source for the dermal absorption of soluble arsenic in water and soil.
With a radio-labeled arsenic mass-balance study, the results from this
study suggested that mean dermal absorption rates for soluble arsenic
were in the range of 2.0–6.4 percent of the applied dose for rhesus
monkeys.  Based on Wester et al. (1993), the Panel recommended using 2-3
% of dermal absorption rate for arsenic residue on the surface of wood.

Recently, using chemical analysis approach instead of using a
radio-labeled mass balance approach, Wester et al. (2004) and  Lowney et
al (2007) measured the dermal absorption of CCA-treated wood residues
and arsenic-containing soil in the rhesus monkey, and found  that
arsenic dermal absorption from both CCA-treated wood surface residue and
arsenic containing soil was much lower (approximately 0.01% for
CCA-treated wood residues and 0.5% or less for arsenic containing soil )
compared to the results published by Wester et al. (1993) for arsenic in
water.  The issue about the appropriateness of using the lower dermal
absorption factor (0.01%) was discussed in the 2003 SAP.

The Panel found three areas of concern with respect to the 2004 Wester
et al. study. These were:

a) Generic experimental issues such as sample size (n=3) and the absence
of a mass balance, the former limiting statistical power and the latter
being a significant shortcoming considering the use of an in vivo
primate protocol

b) The ACCR-skin contact scenario - the intimacy of contact between ACCR
and skin was less certain than that for arsenic in aqueous solution (5
µL/cm2). Also compounds with negligible vapor pressures can only be
transferred by direct contact or liquid phase diffusion and even a very
thin gap between the external medium and skin could represent an
absolute barrier to transport of non-volatiles (such as inorganic
arsenic). Hence the vertical configuration employed by Wester et al. was
not recommended. The Panel also stated that the authors overestimated
the mass of ACCR required to calculate monolayer covering.

c) Pharmacokinetics of absorbed arsenic – Wester et al. (1993 and
2003) adjusted their results using urinary recovery of arsenic following
intravenous injection of soluble arsenic. However, it is unknown whether
this adjustment is appropriate following dermal application since
binding of arsenic by keratin in skin may delay excretion or following
dermal absorption the fate of complexed arsenic may be different than
that of inorganic arsenic.

Given the uncertainties discussed above, the Panel decided that “no
quantitative estimate of dermal availability from ACCR could be derived
from the 2003 Wester et al. experiments. The Wester et al. (2003) study
was thus insufficient grounds to alter the dermal bioavailability
assumption used SHEDS-Wood.”

SAP concluded that “although this remains an area of uncertainty,
research in this laboratory, using radiolabeled arsenic (Wester et al.,
1993), suggests that this is a reasonable assumption for assessing the
urinary excretion fraction of any absorbed dose of arsenic.”

Although there are limitations in both Wester et al. (2004) and Lowney
et al (2007) studies, the results indicate that the urinary arsenic
levels following topical administration of arsenic in CCA residues are
not distinguishable from background, the non-zero values for background
urinary arsenic excretion, and the variability of the measured
background values, impose some limits regarding the sensitivity of the
model to detect an absorbed dose.

Comment: The PRA documentation should acknowledge the substantial debate
that surrounds evaluations of arsenic carcinogenicity (particularly in
determining appropriate approaches for quantifying potential
carcinogenic risks associated with oral arsenic exposure) and the risk
assessment approach applied in the PRA should be modified to reflect the
results of numerous rigorous new epidemiological studies that have been
issued in the last several years and which indicate that the PRA
approach is likely to overestimate arsenic carcinogenic risks.

EPA Response:  The Agency is aware of the substantial debate that
surrounds evaluations of arsenic carcinogenicity. This is the reason
that, in September 2005, EPA scientists presented the proposed approach
in the dose response assessment of cancer effects for inorganic arsenic
to the Science Advisory Board (SAB).  Linear dose response was selected
for inorganic arsenic-induced bladder and lung cancer.  The SAB
Committee released its final report in 2007 and indicated that the
proposed approaches for dose response modeling for the inorganic arsenic
cancer assessments is supported by the available information.   SAB
concluded that the southwestern Taiwan data set still remains the
appropriate dataset for cancer risk.  Inorganic arsenic has the
potential for a highly complex mode of action in causing different forms
of cancer.  Indirect genotoxicity suggests a threshold, but studies do
not show where the threshold might be or the shape of the dose-response
curve at low dose levels. SAB (2007) concluded that use of a linear
model until more is learned about the pharmacokinetics and
pharmacodynamics in the causation of different forms of cancer in human
population.

Human Exposure Comments and Responses

Comment: Analysis should reflect the changes in exposures resulting from
the voluntary cancellation.

EPA Response:  The final assessment will reflect the changes in exposure
resulting from the voluntary cancellation.

Comment: The risk assessment should cover shellfish consumption because
both humans and wildlife consume shellfish from shoreline areas where
treated wood is used.

EPA Response:  Very little CCA is expected to leach from treated wood
and any CCA that might leach would be heavily diluted by adjacent water
bodies.  Because significant contribution to food or drinking water is
not expected from the currently registered uses and because no tolerance
exists for CCA, a dietary risk assessment is not appropriate.

Comment: There are important characteristics about ACZA and the
treatment process that require adjustments in the exposure and risk
estimates.

EPA Response:  The Agency appreciates the clarification provided will
take these comments under consideration in characterizing differences in
formulation, wood treatment use patterns, and in deriving ACZA and CCA
dose estimates for treatment plant workers in the final version of the
occupational exposure chapter.

Comment: When interpreting the results of the exposure and risk
analyses, OPP should recognize observed differences among different
types of wood treating facilities.

EPA Response:  Worker exposures were determined by using the geometric
mean exposure values for monitored workers from all study test sites
(i.e., Sites A, B, and C).  The Agency is in the process of evaluating
the differences in monitored worker exposures between sites across
similar job functions and will reexamine the worker study data to refine
the assessment.  This refinement will capture, where appropriate, the
differences between sites (e.g., pesticide concentrations, cycle
duration) which may impact exposures and revise the ORE accordingly.

Comment: EPA omits a number of recent studies that substantially alter
the conclusions that should be drawn regarding the potential health
risks associated with the evaluated exposure scenarios.

EPA Response:  The final CCA risk assessments will be based on the most
up-to-date information including consideration of recent studies.

Worker Study Review Comments and Responses

Comment: Requested unit of exposures measurement is in the report but is
not relevant for exposures at wood treating facilities.

EPA Response:  This was noted during the previous review as an issue
and, at the time, the Agency was interested in relating monitored
exposure to unit exposure such as mg/lb a.i. to gauge differences in
CCA/ACZA chemical usage and exposures within and between test sites. The
respondent notes that this metric is not suitable because, “unlike an
agricultural field, there is no useful way to quantitatively extrapolate
worker exposure from amount of pesticide used at a wood treating
facility.”  The respondent emphasized differences between ACZA and CCA
treatment processes (amount of arsenic used and length of treatment
cycle) that must be taken into consideration.  The Agency is aware that
a metric based on surrogate UE estimates (mg/lb a.i.) is not appropriate
when actual chemical-specific dermal/inhalation dosimetry data have been
developed, as is the case for this RED.  The Agency is in the process of
reexamining the worker study data to refine exposures in the ORE based
on differences between sites, pesticide concentrations, cycle duration,
and other factors.

Comment: The agricultural use pesticide evaluation process is not
appropriate for arsenical wood preservatives.

EPA Response:  Although the agricultural use pesticide evaluation
process does not take into account every aspect of the CCA wood
preservative uses, this process does provide a reasonable estimate for
potential exposure and risk and is useful for identifying potential
risks that may require mitigation.

Occupational Risk Comments and Responses

Comment: OPP identifies almost all of the carcinogenic risk estimates
associated with arsenic inhalation as being of potential health concern;
however, the PRA fails to note that all of the underlying measured
concentrations of arsenic in air measured in the exposure study used to
estimate inhalation risks are less than occupational standards
established by OSHA.

EPA Response:  The Agency will include references to the applicable
occupational standards established by OSHA.

Comment: MOE values selected for use in analyses should reflect the
substantial database of information that is available regarding the
toxicity of arsenic in human populations.

EPA Response:  The Agency relies on the best available toxicity data for
risk assessment purposes and reflects a consideration of the available
data regarding toxicity of arsenic in human populations.

Environmental Risk Comments and Responses

Comment: Because available environmental data for arsenic indicate that
the concentrations of total arsenic in marine and estuarine bivalve
mollusks greatly exceed those in freshwater fish, evaluating risks to
saltwater shellfish should be a high priority.

EPA Response: While it is true that some data appear to show that total
arsenic concentration in some marine and estuarine bivalves may exceed
those in the freshwater fish, the Agency is cognizant of the fact that
there are many sources for the presence of arsenic in water bodies.
There is very little quantitative information available (data, research,
monitoring) linking arsenic in water bodies to potential anthropogenic
sources (e.g., industrial, pesticidal).

Available studies indicate that any potential release of metals from CCA
treated wood would be highest for the first few days and minimal
thereafter. Therefore, any presence of metals that leach from CCA
treated wood would be expected to be episodic and heavily diluted by the
surrounding water.

Comment: EPA should compare estimated environmental concentrations of
arsenic and chromium from wood preservatives use to its water quality
objectives. Any anticipated exceedance of these objectives has potential
environmental and regulatory consequences that should be identified in
the risk assessment and addressed with mitigation in the Registration
Eligibility Decision.

EPA Response: Currently it is not possible to conduct a reliable risk
assessment for metals released by CCA treated wood into marine
environments because there is such large uncertainty associated with
estimating arsenic and chromium concentrations from pesticidal and/or
other exposure sources. In addition, release of these metals into marine
environment is expected to be episodic and may subsequently undergo
speciation which may or may not make the compounds largely bioavailable
to the marine organisms.

Comment: EPA should incorporate a comprehensive review of the open
literature in its risk assessments.

EPA Response: The Agency evaluated the open literature and included
relevant information the ecological risk assessment.

Comment: EPA should require fulfillment of all data requirements related
to aquatic toxicity including those relevant to estuarine and marine
mollusks.

EPA Response:  The Ecological Hazard and Environmental Risk Assessment
RED chapter for CCA addresses the need for confirmatory sediment
toxicity, non-target plant toxicity, and avian reproduction studies.

Comment: EPA should assess risk to the hard-substrate community.

EPA Response: To the extent possible based on available information, the
Ecological Hazard and Environmental Risk Assessment RED chapter for CCA
addresses impacts to the hard-substrate aquatic community.

Comment: EPA should estimate surface water pollutant concentrations from
use of wood preservatives at urban shorelines where runoff (from distant
as well as near-shore areas) flows untreated to surface water. EPA
should compare these estimated concentrations to the EPA-required water
quality criteria. Any exceedance of these criteria should be identified
in the risk assessment and eliminated with required mitigation in the
Registration Eligibility Decision.

EPA Response: Based on available literature, EPA acknowledges that wood
preservative uses like CCA may contribute to arsenic, chromium, and
copper in surface water.  To the extent possible based on available
data, the Agency will estimate potential contributions to surface water
to determine whether or not wood preservative uses of CCA would cause
unreasonable adverse effects to human health or the environment as
required by FIFRA.

Comment: EPA could have developed a risk assessment from available data.

EPA Response: Currently available models are not suitable for aquatic
risk assessment of CAA wood preservative uses.  The Agency is currently
developing a Biotic Ligand Model which, in the future, could potentially
be used for such uses.

Comment: EPA must be transparent on estimated environmental
concentrations (EEC).

EPA Response: Available avian and mammalian EECs are presented in the
Ecological Hazard and Environmental Risk Assessment RED chapter for CCA.

Benefits and Alternatives Response

Several respondents raised questions regarding potential benefits and
alternatives to CCA as a wood preservative.  These issues raised in
these comments will be addressed in the 2008 document titled “A
Qualitative Economic Impact Assessment of the Use of Alternatives to CCA
as a Wood Preservative.”

Risk Mitigation Response

Several respondents offered suggestions for mitigating risks posed by
CCA-treated lumber.  Upon finalization of the risk assessment, EPA will
evaluate the appropriateness of these and other measures in its
reregistration eligibility decision (RED) document.

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