[Federal Register Volume 79, Number 161 (Wednesday, August 20, 2014)]
[Rules and Regulations]
[Pages 49239-49244]
[FR Doc No: 2014-19554]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R10-OAR-2013-0713; FRL-9915-40-Region 10]

Approval and Promulgation of Implementation Plans; Washington:
Kent, Seattle, and Tacoma Second 10-Year PM10 Limited
Maintenance Plan

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: The EPA is approving a limited maintenance plan submitted by
the State of Washington on November 29, 2013, for the Kent, Seattle,
and Tacoma maintenance areas for particulate matter with an aerodynamic
diameter less than or equal to a nominal 10 micrometers
(PM10). The EPA first identified these areas in 1987 as
potentially violating the 24-hour PM10 national ambient air
quality standard (NAAQS). All three areas have been attaining the NAAQS
since 1990, due to State Implementation Plan (SIP) measures such as a
residential wood smoke control program, a prohibition on outdoor
burning, and industrial controls. The areas were redesignated to
attainment for the 24[hyphen]hour PM10 NAAQS effective May
2001, when the EPA approved the first 10[hyphen]year maintenance plan.
This limited maintenance plan covers the second 10-year maintenance
period ending in May 2021. The EPA received one set of adverse comments
focused primarily on proposed coal export terminals that may be built
in the Pacific Northwest or possible expansion of coal export terminals
in Canada that may impact the three maintenance areas in the future.

DATES: This final rule is effective September 19, 2014.

ADDRESSES: The EPA has established a docket for this action under
Docket ID No. EPA-R10-OAR-2013-0713. All documents in the docket are
listed on the www.regulations.gov Web site. Although listed in the
index, some information is not publicly available, e.g., Confidential
Business Information (CBI) or other information the disclosure of which
is restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available either electronically through www.regulations.gov or in hard
copy at the Air Programs Unit, Office of Air Waste and Toxics, EPA
Region 10, 1200 Sixth Avenue, Seattle, WA 98101. The EPA requests that
if at all possible, you contact the individual listed in the FOR
FURTHER INFORMATION CONTACT section to view the hard copy of the
docket. You may view the hard copy of the docket Monday through Friday,
8:00 a.m. to 4:00 p.m., excluding Federal holidays.

FOR FURTHER INFORMATION CONTACT: Jeff Hunt at telephone number: (206)
553-0256, email address<EMAIL_ADDRESS>or the above EPA, Region 10
address.

SUPPLEMENTARY INFORMATION:

Definitions

    For the purpose of this document, we are giving meaning to certain
words or initials as follows:
    (i) The words or initials ``Act'' or ``CAA'' mean or refer to the
Clean Air Act, unless the context indicates otherwise.
    (ii) The words ``EPA'', ``we'', ``us'' or our mean or refer to the
United States Environmental Protection Agency.
    (iii) The initials ``SIP'' mean or refer to State Implementation
Plan.
    (iv) The words ``Washington'' and ``State'' mean the State of
Washington.

Table of Contents

I. Background Information
II. Response to Comments
III. Final Action
IV. Statutory and Executive Orders Review

I. Background Information

    On August 7, 1987, the EPA identified portions of Kent, Seattle,
and Tacoma as ``Group I'' areas of concern for having a greater than
95% probability of violating the 24-hour PM10 NAAQS (52 FR
29383). On November 15, 1990, the Group I areas of Kent, Seattle, and
Tacoma were designated as nonattainment for PM10 by
operation of law upon enactment of the Clean Air Act Amendments. The
Washington Department of Ecology (Ecology) and the Puget Sound Clean
Air Agency (PSCAA) worked with the communities of Kent, Seattle, and
Tacoma to establish PM10 pollution control strategies.
Primary control strategies for the three areas included a residential
wood smoke control program, a prohibition on open burning, and
industrial emission controls. These control measures were highly
successful, with monitoring data showing Kent, Seattle, and Tacoma
meeting the PM10 NAAQS since 1987, 1990, and 1989,
respectively, with further declines in PM10 levels in
subsequent years.
    The EPA fully approved the PM10 attainment plans for
Kent, Seattle, and Tacoma on July 27, 1993, October 26, 1995, and
October 25, 1995, respectively (58 FR 40059, 60 FR 54812, and 60 FR
54599). The EPA then approved a 10-year maintenance plan redesignating
all three areas from nonattainment to attainment, making them
maintenance areas effective May 14, 2001 (66 FR 14492). The limited
maintenance plan that the EPA is approving in this final rule was
submitted to fulfill the second 10-year planning requirement in section
175A(b) of the Clean Air Act, to ensure compliance with the
PM10 NAAQS through May 14, 2021. The EPA proposed approval
of this limited maintenance plan on December 26, 2013 (78 FR 78311).

II. Response to Comments

    On March 10, 2014, the EPA received one set of comments opposing
the EPA's proposed approval of the PM10 limited maintenance
plan for Kent, Seattle and Tacoma. The comments primarily focus on the
potential impact that three coal export terminals, proposed to be built
in the Pacific Northwest, could have on PM10 concentrations
in the maintenance areas. The commenter also raises the possibility of
other similar impacts if there is an increase in locomotive traffic
related to tar sands/oil shipments or expansion of Canadian coal export
terminals. Lastly, the commenter questions the methodology used by the
EPA, PSCAA, and Ecology in estimating emissions in the 2011 emissions
inventory from current rail traffic to Canadian coal export terminals
that may pass through the maintenance areas.
    These comments are similar to comments previously submitted on
February 22, 2013, related to emissions impacts of locomotive coal
transport in the emissions inventory for the Tacoma fine particulate
matter (PM2.5) nonattainment area (Docket No. EPA-R10-OAR-
2012-0712). The EPA responded to these comments in the May 29, 2013
final rulemaking approving the inventory explaining that we found no
trends of increased PM2.5 impacts from coal dust at the
chemical speciation monitor using data as of 2011, or increases in
ambient concentrations of PM2.5 generally, corresponding to
the increased locomotive traffic from 2008 to 2011

cited by the commenter (78 FR 32131).\1\ The EPA also notes that the
Washington State Environmental Policy Act (SEPA) and the National
Environmental Policy Act (NEPA) processes for reviewing coal export
proposals cited in the February 22, 2013 letter are ongoing. The EPA
concluded that many of the issues raised by the commenter about the
potential impacts of future projects were beyond the scope of the EPA's
action on the Tacoma PM2.5 nonattainment area control
measures and baseline emissions inventory.
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    \1\ See Tacoma PMF Soil Results included in Docket No. EPA-R10-
OAR-2012-0712.
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    Due to the limited nature of this final action, we are only
responding to those comments directly relevant to the Kent, Seattle,
and Tacoma second 10-year maintenance plan for PM10. In
reviewing the geographic distance and the likely rail routes, the EPA
does not expect significant PM10 impacts to the Kent,
Seattle, and Tacoma maintenance areas from the terminal proposals for
Longview, Washington or Port of Morrow, Oregon cited by the commenter.
Other potential future impacts, such as proposals for the Gateway
Pacific Terminal at Cherry Point, Washington or the expansion of
Canadian terminals, are not far enough along in their development that
the scope or impact of their emissions can be estimated with any degree
of certainty. For example, the commenter questions future impacts from
empty rail cars returning through the maintenance areas if the Gateway
Pacific Terminal is constructed or if rail traffic increases due to the
expansion of Canadian terminals. However, it is not known whether empty
rail cars would return through the maintenance area or whether the
empty cars could use the more direct but mountainous route that
bypasses the maintenance area entirely. Such future route decisions
will depend on several rail system factors.
    Similarly, it is also unclear whether terminal operators would
implement measures to address potential fugitive dust. As noted by the
commenter, the draft Environmental Impact Statement (EIS) for the
Gateway Pacific proposal will not be complete for at least another year
and it is uncertain if washing of rail cars or other measures to reduce
fugitive dust would be implemented should that facility be built. Given
the range of uncertainty surrounding the proposed terminals, including
whether the terminals will be constructed, the location(s) of such
terminals, and decisions of terminal and railway operators that would
affect rail routes, locomotive emissions and fugitive dust emissions,
the EPA believes the level of project-specific inquiry suggested by the
commenter is beyond the scope of the Kent, Seattle, and Tacoma second
10-year maintenance plan for PM10.
    Accordingly, the EPA is responding to four parts of the March 10,
2014 comments that are pertinent to the limited maintenance plan:
Ensuring maintenance through the second 10-year maintenance period, the
EPA's approval of a monitoring system modification for PM10,
the proximity of monitors for determining compliance with the
PM10 NAAQS, and the adequacy of the State's current
emissions inventory for PM10.

A. Ensuring Maintenance Through the Second 10-Year Maintenance Period

    Comment: The commenter is concerned that proposed coal export
terminals, such as the proposed Gateway Pacific Terminal at Cherry
Point near Bellingham, Washington, could have dramatic impacts on the
Kent, Seattle, and Tacoma PM10 maintenance areas if the
terminals were to be approved and constructed as proposed.
Specifically, the commenter is concerned that, if constructed, the
proposed terminals could result in greater coal train traffic through
the maintenance areas with corresponding increases in locomotive and
fugitive coal dust emissions that could raise PM10
concentrations in the area. The commenter also raises concern that the
expansion of existing Canadian coal export terminals or increased
shipments of tar sand and/or Bakken oil to refineries could cause
similar increases in PM10. The commenter claims that because
the PM10 limited maintenance plan for Kent, Seattle and
Tacoma does not fully account for potential increases in locomotive and
fugitive coal dust emissions should the proposed terminals be
constructed, or existing facilities expanded, it does not ensure
maintenance and therefore must be disapproved by the EPA. The commenter
further states that the maintenance plan and contingency measures do
not contain regulatory mechanisms to address potential increases in
PM10 during the maintenance period.
    Response: Many of the proposed coal export terminals cited by the
commenter are undergoing NEPA and/or SEPA review and it is not known
whether the facilities will be constructed, and if they are
constructed, the size and scope of operations that would be authorized.
Nor is there certainty about other projects cited by the commenter,
such as the expansion of Canadian export terminals or the potential
future growth in the shipment of oil to refineries. In addition, as the
commenter notes, there are several possible rail routes that could be
used and it is not known whether locomotive traffic associated with
coal or oil shipments would traverse or bypass the maintenance areas
or, as may be the case, whether routes would constantly vary based on
decisions by the rail operator.
    At this time, due to the speculative nature of the projects,
neither PSCAA nor Ecology can reasonably evaluate the potential impact
of the projects on future emissions growth in the maintenance areas.
However, based on our experience to date with these areas, we believe
the dramatic PM10 impacts forecasted by the commenter are
likely overstated. A recent study entitled Diesel Particulate Matter
Emission Factors and Air Quality Implications from In-Service Rail in
Washington State, USA by Daniel A. Jaffe, et al. (``the Jaffe study'')
measured a PM10 to PM2.5 ratio of 1.15 for coal
trains.\2\ This means that the vast proportion (87%) of the total
PM10 mass measured from coal trains in the Jaffe study was
PM2.5, with only a minor fraction (13%) of particulate mass
falling within the PM2.5 to PM10 range. As noted
in the previous May 29, 2013 response to the commenter, the EPA found
no trend of increased PM2.5 impacts from coal dust at the
Tacoma chemical speciation monitor using data as of 2011, or increases
in ambient concentrations of PM2.5 generally, corresponding
to the increased locomotive traffic from 2008 to 2011 (78 FR 32131).\3\
Using the close relationship between PM10 and
PM2.5 found in the Jaffe study, the EPA would expect that
any dramatic rise in PM10 levels would have a corresponding
rise in PM2.5 levels. Instead, after accounting for year-to-
year meteorological variations, the general PM2.5 trend
appears to be declining despite increased coal export traffic between
2008 and the present.
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    \2\ Calculated from Figure 7, Jaffe, D. A., H. Greg, S.
Malashanka, J. Putz, J. Thayer, J. L. Fry, B. Ayres, J. R. Pierce,
Diesel particulate matter emission factors and air quality
implications from in-service rail in Washington State, USA,
Atmospheric Pollution Research 5, 344-351, 2014.
    \3\ See Tacoma PMF Soil Results included in Docket No. EPA-R10-
OAR-2012-0712.
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    The EPA also reviewed Federal Reference Method (FRM) and Federal
Equivalent Method (FEM) monitored PM10 and PM2.5
levels at the nearby Beacon Hill monitoring site which is located
approximately one mile from the rail lines that pass through
Seattle.\4\ In recent years, 2011 to 2014, there have been no
observations of PM10 at the

Beacon Hill FRM monitor above 35 [mu]g/m\3\, let alone the
PM10 standard of 150 [mu]g/m\3\. In addition, while the rail
transport of coal is new to the Kent, Seattle, and Tacoma maintenance
areas, rail traffic of coal nationally, including Powder River Basin
(PRB) coal, is not. In considering the dramatic rise in future
PM10 emissions predicted by the commenter, the EPA would
expect to have recorded observations of similar dramatic
PM10 impacts at monitors in other areas of the nation,
especially the East and Midwest where heavy rail traffic of coal has
been prevalent for decades. The EPA is not aware of any current
monitors exhibiting such dramatic PM10 impacts from coal
train dust.
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    \4\ See Beacon Hill monitoring included in the docket for this
action.
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    The EPA, Ecology, and PSCAA are fully committed to ensuring
maintenance through the second 10-year maintenance period. Contrary to
the commenter's assertion, the qualification criteria for the limited
maintenance plan option do provide a regulatory mechanism to address
the commenter's primary concern that rapid and significant increases in
locomotive and fugitive coal dust emissions could result in an
exceedance of the PM10 NAAQS. Under the August 9, 2001
limited maintenance plan guidance (Memorandum from Lydia Wegman,
Director, Air Quality Standards and Strategies Division, titled
``Limited Maintenance Plan Option for Moderate PM10
Nonattainment Areas''), as part of the qualification criteria, the EPA
sets a 5-year average margin of safety threshold of 98 [mu]g/m\3\, well
below the 150 [mu]g/m\3\ 24-hour PM10 NAAQS. To continue
qualifying for the limited maintenance plan option, a state is required
to recalculate the 5-year average PM10 emissions annually to
assure the averages for the areas continue to remain below the 98
[mu]g/m\3\ margin of safety. Emission increases that result in an
exceedance of the 98 [mu]g/m\3\ margin of safety require a state to
take actions to reduce PM10 concentrations and provide one
additional opportunity to requalify for the limited maintenance plan
option. If efforts to reduce PM10 concentrations fail, or if
they succeed but the area continues to experience increases in
PM10 concentrations, the limited maintenance plan option
will no longer be available and a state will be required to submit a
full maintenance plan, including a maintenance demonstration and
adequate contingency measures, within 18 months.
    The estimated 5-year average PM10 design values in the
areas are: 463 [mu]g/m\3\ for Kent, 505 [mu]g/
m\3\ for Seattle, and 588 [mu]g/m\3\ for Tacoma (estimated
using a PM2.5 correlation method discussed in more detail
below). Even assuming a certain level of statistical error, all of
these estimates are well below both the 98 [mu]g/m\3\ margin of safety
and the 150 [mu]g/m\3\ 24-hour NAAQS. In its limited maintenance plan
submission, PSCAA committed to conduct an annual recalculation of the
3-year and 5-year design value estimates. Any increases in future
estimated design values provide PSCAA an opportunity to assess and
address PM10 increases to continue qualifying for the
limited maintenance plan option. Based on the data and trends for the
Kent, Seattle, and Tacoma maintenance areas, the EPA believes that the
limited maintenance plan is protective of the PM10 NAAQS. If
the projects cited by the commenter are built and cause a corresponding
increase in PM10 concentrations such that the margin of
safety is exceeded, the limited maintenance plan requires appropriate
consequences that would address the increase in PM10
concentrations and/or revoke the area's ability to qualify for a
limited maintenance plan and require a full maintenance plan within 18
months.
    Lastly, based on our review of the data and emission sources, a
violation of the 24-hour PM2.5 standard would happen well
before a potential violation of the 24-hour PM10
standard.\5\ The PM10 to PM2.5 correlation
analysis provided in the limited maintenance plan shows that
PM2.5 levels would need to reach 122 [mu]g/m\3\ for Kent,
113 [mu]g/m\3\ for Seattle, and 114 [mu]g/m\3\ for Tacoma before a
violation of the 24-hour PM10 standard is likely. Even
factoring in the commenter's doubts about the accuracy of the
correlation analysis discussed below, these estimates provide a
significant margin of safety considering the 24-hour PM2.5
standard of 35 [mu]g/m\3\. As shown in the Jaffe study, and based on
our knowledge of sources in these maintenance areas, PM10
and PM2.5 emissions are closely intertwined. Any effort to
address PM2.5 nonattainment would have the co-benefit of
reducing PM10.
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    \5\ See page 26 of the SIP submittal and the discussion on
PM10/PM2.5 correlation in the section below.
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    In considering all the factors described above, the EPA has
determined that a limited maintenance plan that relies on the 98 [mu]g/
m\3\ margin of safety threshold for PM10 is both reasonable
and protective in ensuring continued maintenance, even as the mix of
emission sources may change over time.

B. The EPA's Approval of a Monitoring System Modification for PM10

    Comment: The commenter raises concern that monitoring which relies
on current PM2.5 monitors and historical PM10 and
PM2.5 correlation data does not accurately capture the
effects of changing PM10 emissions over time from sources
such as fugitive coal dust or other particulate matter from increased
locomotive traffic. The commenter also questions the accuracy of the
PM10 and PM2.5 correlation analysis, noting
specific data points where the monitored observation greatly exceeded
the statistical modeling estimate.
    Response: As described in the EPA's December 26, 2013 Federal
Register publication, the EPA proposed approval of a monitoring system
modification under 40 CFR 58.14(c)(3) which states that any state or
local air monitor station (SLAM) may be discontinued for any pollutant,
provided the monitor has not measured violations of the applicable
NAAQS in the previous five years, and the approved SIP provides for a
specific, reproducible approach to representing the air quality of the
affected county in the absence of actual monitoring data. See 78 FR
78311. In the case of the Kent, Seattle, and Tacoma maintenance areas,
the EPA proposed using existing PM2.5 monitors and
correlated PM10 and PM2.5 data to estimate
PM10 emissions. The EPA agrees with the commenter that
PM10 and PM2.5 correlations do vary over time and
location as the mix of emission sources change. However, for the
reasons described below, the EPA has determined that the monitoring
system modification proposed under 40 CFR 58.14(c)(3) is both
technically sound and protective of human health and the environment
with respect to the PM10 NAAQS.
    Ecology, as part of the approved monitoring network plan, maintains
collocated PM10 and PM2.5 FRM and FEM monitors at
the nearby Beacon Hill site in Seattle.\6\ This monitoring site
provides the EPA access to ongoing collocated PM10 and
PM2.5 data, similar to the historical data calculated for
the Kent, Seattle, and Tacoma maintenance areas. Following the same
methodology used by PSCAA and Ecology, the EPA calculated Beacon Hill
PM10 to PM2.5 ratios for the winter period using
2003-2006 data (0.99) and 2011-2013 data (1.37). PSCAA and Ecology's
calculated PM10 to PM2.5 ratios for Kent (1.22),
Seattle (1.26), and Tacoma (1.29) all fall with the range of the Beacon
Hill data for the winter period calculated by the

EPA. In the summer period, the EPA also calculated Beacon Hill
PM10 to PM2.5 ratios for 2003-2006 data (1.57)
and 2011-2013 data (1.70). The historical summer PM10 to
PM2.5 ratios calculated by PSCAA and Ecology for Kent
(2.07), Seattle (1.83), and Tacoma (2.44) are all greater than the
PM10 to PM2.5 ratio calculated by the EPA for
Beacon Hill (i.e., the PSCAA and Ecology PM10 to
PM2.5 ratios likely err on the side of overestimating
PM10 relative to the results calculated by the EPA).
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    \6\ 2012 Ambient Air Monitoring Network Report and October 25,
2012 Network Approval Letter, included in the docket for this
action.
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    The information above is relevant because the Jaffe study found
that the vast proportion (87%) of the total PM10 mass
measured from coal trains was PM2.5. Over time, if rail
traffic of coal becomes a more dominant factor in the emissions mix as
suggested by the commenter, the PM10 to PM2.5
ratio will be driven closer to the 1.15 ratio found in the Jaffe
study.\7\ Thus, the PM10 to PM2.5 ratios used for
Kent (2.07), Seattle (1.83), and Tacoma (2.44) will likely err on the
side of overestimating PM10 levels and are inherently more
protective than the ratio measured in the recent Jaffe study for coal
train emissions. It is also important to note that the nephelometers
used by PSCAA in all three maintenance areas measure light scatter at
one second intervals and do not exclude the PM2.5-10
particle range. Therefore, the commenter's concern about a sudden burst
of coal dust in the PM2.5-10 particle range would indeed be
measured by the instruments.
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    \7\ Calculated from Figure 7, Jaffe, D. A., H. Greg, S.
Malashanka, J. Putz, J. Thayer, J. L. Fry, B. Ayres, J. R. Pierce,
Diesel particulate matter emission factors and air quality
implications from in-service rail in Washington State, USA,
Atmospheric Pollution Research 5, 344-351, 2014.
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    Finally, the commenter questions the accuracy of the
PM10 and PM2.5 correlation analysis, noting
specific data points where the monitored observation exceeded the
statistical modeling estimate. The EPA raises two points in response to
this comment. First, the exact statistical fit of each data point is
less important than ensuring there is no bias in the models. In this
case, the EPA is satisfied that the slopes calculated by PSCAA are
representative of the data (i.e. for the outlier data points identified
by the commenter where the models underestimate actual PM10
emissions, the EPA can find an equal balance of data points where the
models overestimate actual PM10 emissions). Second, concern
over the statistical fit of the models might be greater but for the
fact that all of the data points collected over the entire eight years
of collocated monitoring, including the outliers identified by the
commenter, were all well below the 150 [mu]g/m\3\ NAAQS and also below
the 98 [mu]g/m\3\ margin of safety. Considering the form of the
PM10 NAAQS, which allows a certain degree of outliers, the
EPA believes it is highly unlikely that use of the statistical
correlation would result in undetected violations of the
PM10 NAAQS.\8\
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    \8\ The twenty-four-hour average concentration of
PM10 in the ambient air must not exceed 150 [mu]g/m\3\
more than one time per year, on a three-year average.
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    The EPA recognizes the importance of FRM and FEM monitoring. The
limited maintenance plan includes a trigger to reestablish FRM or FEM
PM10 monitoring should PM10 levels reach the 98
[mu]g/m\3\ margin of safety threshold. Reestablishing the FRM and FEM
above the margin of safety means that violations of the PM10
NAAQS and triggers for contingency measures would be assessed using
PM10 monitoring data collected by an FRM or FEM. However,
the EPA also recognizes that federal, state, and local monitoring
resources are finite. Agency resources to reestablish FRM or FEM
PM10 monitoring, as requested by the commenter, would likely
be at the expense of PM2.5 monitoring or other important
monitoring needs. Considering the far more pressing and likely greater
risks posed by PM2.5 as described above, the EPA is
approving the monitoring system modification under 40 CFR 58.14(c)(3).

C. The Proximity of Monitors for Determining Compliance With the PM10
NAAQS

    Comment: The commenter broadly asserts that the monitoring system
modification proposed by the EPA violates 40 CFR part 58, Appendix D
for comparing an area's air pollution levels to the NAAQS, as discussed
above. Included in the commenter's discussion are concerns that, the
``EPA offers no evidence that the placement of the monitors is
appropriate for monitoring the trains'' and ``[t]he Kent monitor is a
neighborhood scale site to be representative of the Kent Valley Area,
not coal trains.''
    Response: Many of the issues raised by the commenter, such as the
request for trackside microscale monitoring, are discretionary state or
local agency choices rather than a failure on the part of Washington to
meet 40 CFR part 58, Appendix D requirements. Appendix D to Part 58--
Network Design Criteria for Ambient Air Quality Monitoring describes
how data from FRM, FEM, and approved regional method (ARM) monitors
will be used for comparing an area's air pollution levels to the NAAQS.
Section 4.6 of the Pollutant-Specific Design Criteria for SLAMS Sites
contains the specific requirements for PM10. As discussed in
section 4.6(b), the EPA determined that the most important spatial
scales to effectively characterize the emissions of PM10
from both mobile and stationary sources are the middle scales and
neighborhood scales. Section 4.6(b)(c) describes the use of
neighborhood scale monitors for compliance with the NAAQS.
    The Kent monitor, although designated as a neighborhood scale
monitor, is almost immediately adjacent to the railroad tracks, less
than 0.2 miles according to the scale in Figure 2.1 of the State's
submittal. The Seattle and Tacoma monitors are similarly located near
railroad corridors reflecting the industrial nature of the previous
PM10 nonattainment areas. While the Seattle and Tacoma
monitors are likely too far away to detect immediate fence line
microscale impacts from rail traffic, they meet the middle scale
criteria described in section 4.6(b)(3). Under section 4.6(b)(3) the
EPA determined that much of the short-term public exposure to
PM10 is on the middle scale and on the neighborhood scale.
    The EPA regulations state that the middle scale and neighborhood
scale monitors are most important for determining compliance with the
NAAQS. This is not to dismiss the impact to environmental justice or
other sensitive populations from microscale impacts. The Jaffe study
found that, ``[f]or the one month of measurements at the Seattle site,
the average PM2.5 concentration was 6.8 [mu]g/m\3\ higher
near the rail lines compared to the average from several background
locations.'' Multiplying this 6.8 [mu]g/m\3\ increase in
PM2.5 levels times the PM10 to PM2.5
ratio for coal trains found in the Jaffe study (the highest ratio of
all the train types analyzed, and therefore the most conservative ratio
to use here) yields an estimated PM10 level of 7.82 [mu]g/
m\3\ at the immediate fence line. Even factoring in increased
locomotive growth at this conservative level, the extra increment
necessary to violate the 150 [mu]g/m\3\ PM10 NAAQS is
unlikely, given our understanding of current PM10 design
values of 46  3 [mu]g/m\3\ for Kent, 50  5
[mu]g/m\3\ for Seattle, and 58  8 [mu]g/m\3\ for Tacoma.

D. The Adequacy of the State's Current Emissions Inventory for PM10

    Comment: Setting aside the broader issue of future growth in
emissions, the commenter criticizes the methodology used by the State
to estimate the 2011 emissions inventory, particularly

emissions of fugitive dust from coal trains.
    Response: In responding to previous emissions inventory concerns
submitted by the commenter regarding the 2008 baseline emission
inventory for the Tacoma PM2.5 nonattainment area, the EPA
stated:

    As noted in the proposal for this action, the EPA referred to
the August 2005 ``Emissions Inventory Guidance for Implementation of
Ozone and Particulate Matter NAAQS and Regional Haze Regulations''
(hereafter ``emissions inventory guidance'' or ``guidance''), to
assess the adequacy of Washington's submission. The guidance covers
several elements related to this comment. First, the mobile source
section in the guidance contains no discussion or requirement for
calculating fugitive dust from locomotive payloads. Instead,
fugitive dust emissions from all source categories are discussed in
section 5.4 of the guidance addressing nonpoint sources. The
guidance states, ``[n]onpoint sources are generally described as
those sources that are too small, numerous, or difficult to be
inventoried individually. Potential nonpoint sources of emissions
are given in Table 5.4-1 and potential crustal (dust) sources of PM
emissions are in Table 5.4-2. These tables are presented as guides
to assist State, local and Tribal agencies in focusing their
nonpoint source emission inventory efforts.'' The guidance goes on
to state, ``[t]he State, local and Tribal agencies may want to
concentrate their efforts on the most significant source
categories.'' The guidance acknowledges that States cannot
individually inventory all nonpoint source emissions, but should use
the best available data to inform which nonpoint source categories
to focus on in creating a comprehensive and accurate inventory of
actual emissions.\9\
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    \9\ 78 FR 32131, May 29, 2013.

    For the Kent, Seattle, and Tacoma PM10 maintenance
areas, PSCAA and Ecology requested the EPA's assistance in estimating
possible fugitive coal dust emissions from rail transport in the 2011
emissions inventory included in the State's submittal. The EPA
suggested using a paper entitled A Study of Fugitive Coal Dust
Emissions in Canada, November 2001, by Douglas L. Cope and Kamal K.
Bhattacharyya (``the Cope study''). The EPA neither endorses nor
rejects the findings of the Cope study, but merely acknowledges it was
one of the only recent studies the EPA could find at that time on this
topic prior to publication of the recent Jaffe study. Using these
emission factors, the State calculated a modest contribution to overall
PM10 emissions from rail transport of coal including both
diesel emissions and an estimate of potential fugitive dust (Seattle =
5%, Tacoma = 2%, and Kent = 6%, respectively, of overall
PM10 emissions from both diesel emissions and fugitive
dust).
    As a general response to the commenter's concern about the fugitive
dust emissions methodology, the EPA notes that the Cope study and the
Jaffe study contain emission factors for both PM10 and
PM2.5. To the extent that the methodology used by the State
significantly underestimates PM10 emissions, as suggested by
the commenter, the EPA would expect to see similar increases in
PM2.5, particularly for the Kent monitor which is
immediately adjacent to a rail line. For example, the commenter
includes AMS/EPA Regulatory Model (AERMOD) modeling conducted for the
Port of Morrow, Oregon terminal proposal to suggest that the State
underestimated PM10 from fugitive dust and rail emissions in
the 2011 emissions inventory. The modeling submitted was for
PM2.5, with the commenter arguing that AERMOD ``does not
distinguish between PM10 and PM2.5 in terms of
modeled impacts.'' In assessing the predictive accuracy of any model,
it is important to measure against actual monitoring data. In this
case, figures 4.1.1, 4.1.4, and 4.1.7 of the limited maintenance plan
and the nearby Beacon Hill monitoring data show no dramatic increases
of PM2.5 in 2011 or the present. Therefore, the State's
conclusion that PM10 emissions in 2011 from rail transport
of coal constitute a minor proportion of the overall PM10
emissions inventory is consistent with all currently available
monitoring data for both PM10 and PM2.5.
    The commenter also questioned the accuracy of the State's 2011
baseline emissions inventory for using an 85% control factor in
calculating estimated fugitive dust emissions applying the Cope study
methodology. The EPA recalculated the 2011 fugitive dust estimates for
PM10 using the State methodology as well as a scenario
assuming no control, included in the docket for this action. The
difference between the methodology used by the State and the
uncontrolled scenario calculated by the EPA was approximately 17 tons
of cumulative impact for all three maintenance areas, representing 1.2%
of the total PM10 inventory. To be clear, the EPA is not
opining on the validity of the Cope study, the 85% control factor, or
any other analysis or conclusions that may or may not result from the
ongoing NEPA and SEPA evaluation process. The EPA is simply stating
that the generally modest PM10 impacts from fugitive dust
calculated in the 2011 emissions inventory for this limited maintenance
plan appear to be consistent with our calculations and with current
monitoring data, and may in fact overestimate these impacts.
    Lastly, the commenter questions the State's use of the Cope study
in calculating the 2011 emissions inventory because the Cope study does
not factor in the fugitive dust impact of empty rail cars returning
through the maintenance areas. More recent studies from Australia,
included in the docket for this action, suggest that the Cope study
might overestimate fugitive dust PM10 impacts from coal,
finding no statistically significant difference between coal trains
(both loaded and empty) and any other type of freight train.
Specifically, the Australian studies found ``that other contaminants
such as diesel may be of more concern than coal dust. This conclusion
is further supported by the fact that effect sizes were similar for
freight, loaded and unloaded coal trains, all of which are pulled by
diesel locomotives.'' \10\ Considering the study results and current
particulate matter monitoring data, the EPA concludes that the
relatively modest contributions calculated in the State's 2011
emissions inventory represent a good faith effort to quantify fugitive
dust emissions.
---------------------------------------------------------------------------

    \10\ See page 3, Re-analysis of ARTC Data on Particulate
Emissions from Coal Trains, included in the docket for this action.
---------------------------------------------------------------------------

III. Final Action

    The EPA is approving the limited maintenance plan submitted by the
State of Washington on November 29, 2013, for the Kent, Seattle, and
Tacoma PM10 maintenance areas, including approval of a
monitoring system modification for the areas. The EPA's approval of
this limited maintenance plan satisfies the section 175A Clean Air Act
requirements for all three areas, including the portion of the Puyallup
Indian Reservation that falls within the Tacoma PM10
maintenance area.

IV. Statutory and Executive Orders Review

    Under the Clean Air Act, the Administrator is required to approve a
SIP submission that complies with the provisions of the Act and
applicable Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a).
Thus, in reviewing SIP submissions, the EPA's role is to approve State
choices, provided that they meet the criteria of the Clean Air Act.
Accordingly, this action merely approves State law as meeting Federal
requirements and does not impose additional requirements beyond those
imposed by State law. For that reason, this action:

     Is not a ``significant regulatory action'' subject to
review by the Office of Management and Budget under Executive Order
12866 (58 FR 51735, October 4, 1993);
     does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because this action does not involve technical standards; and
     does not provide the EPA with the discretionary authority
to address, as appropriate, disproportionate human health or
environmental effects, using practicable and legally permissible
methods, under Executive Order 12898 (59 FR 7629, February 16, 1994).

In addition, this rule does not have tribal implications as specified
by Executive Order 13175 (65 FR 67249, November 9, 2000), because the
rule neither imposes substantial direct compliance costs on tribal
governments, nor preempts tribal law. Therefore, the requirements of
section 5(b) and 5(c) of the Executive Order do not apply to this rule.
Consistent with EPA policy, the EPA nonetheless provided a consultation
opportunity to the Puyallup Tribe in a letter dated October 18, 2013.
The EPA did not receive a request for consultation.
    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. The EPA will submit a report containing this action and
other required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the Clean Air Act, petitions for
judicial review of this action must be filed in the United States Court
of Appeals for the appropriate circuit by October 20, 2014. Filing a
petition for reconsideration by the Administrator of this final rule
does not affect the finality of this action for the purposes of
judicial review nor does it extend the time within which a petition for
judicial review may be filed, and shall not postpone the effectiveness
of such rule or action. This action may not be challenged later in
proceedings to enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Particulate matter, Reporting and recordkeeping
requirements.

    Dated: August 7, 2014.
Dennis J. McLerran,
Regional Administrator, Region 10.
    40 CFR part 52 is amended as follows:

PART 52--APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS

0
1. The authority citation for part 52 continues to read as follows:

    Authority: 42 U.S.C. 7401 et seq.

Subpart WW--Washington

0
2. Section 52.2470 is amended in paragraph (e) by adding a new entry in
Table 2--ATTAINMENT, MAINTENANCE, AND OTHER PLANS entitled
``Particulate Matter (PM10) 2nd 10-Year Limited Maintenance
Plan'' at the end of the section with the heading ``Attainment and
Maintenance Planning--Particulate Matter''.
    The addition reads as follows:

Sec.  52.2470  Identification of plan.

* * * * *
    (e) * * *

----------------------------------------------------------------------------------------------------------------
                                        Applicable
      Name of SIP provision           geographic or          State       EPA approval date         Comments
                                    nonattainment area  submittal date
----------------------------------------------------------------------------------------------------------------

                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------
                             Attainment and Maintenance Planning--Particulate Matter
----------------------------------------------------------------------------------------------------------------

                                                  * * * * * * *
Particulate Matter (PM10) 2nd 10-  Kent, Seattle, and         11/29/13  8/20/14 [Insert      ...................
 Year Limited Maintenance Plan.     Tacoma.                              Federal Register
                                                                         citation].

                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------

[FR Doc. 2014-19554 Filed 8-19-14; 8:45 am]
BILLING CODE 6560-50-P


Page 1 of 19 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES TXR No. 0054126 MEMORANDUM DATE: March 17, 2006 SUBJECT: Human Studies Review Board: Final Weight of Evidence Comparison of Human and Animal Toxicology Studies and Endpoints for ALDICARB Human Health Risk Assessment [ PC Code: 098301; DP Barcode: D299876] and Discussion of Interspecies Extrapolation in the N Methyl Carbamate Cumulative Risk Assessment [ DP Barcode 321873]

FROM: Linda L. Taylor, Ph. D., Toxicologist Reregistration Branch 1 Health Effects Division ( 7509C)

THRU: Whang Phang, Ph. D., Branch Senior Scientist. Reregistration Branch 1 Health Effects Division ( 7509C)

TO: Tina E. Levine, Ph. D., Director Health Effects Division ( 7509C)

Aldicarb is a N methyl carbamate pesticide that exerts its pesticidal activity and elicits adverse toxic effects by inhibition of cholinesterase activity [ ChEI], which has been demonstrated in whole blood, plasma, red blood cells, and brain of rats, mice, and dogs following acute, subchronic, and chronic exposure and in plasma and RBC in humans following acute exposure.

N methyl carbamate pesticides typically exhibit rapid ChE recovery ( minutes to hours), following maximum inhibition of ChE. The available data indicate a peak effect within an hour of dosing followed by recovery within 24 hours. As a result, a comparable degree of inhibition occurs whether delivered once or following subchronic or chronic dosing.

There is an acute oral exposure study on aldicarb [ MRID 42373001] involving direct dosing of humans in which plasma and RBC cholinesterase activity and Page 2 of 19 clinical signs were monitored. There is also a full database of animal toxicity studies.

OPPTS management has requested that when human studies support a risk assessment, HED should compare the strengths and weaknesses of the human and animal toxicity studies, present how the human studies could be used in endpoint selection, including whether the human data are consistent with animal data in terms of types of effects and effect levels, and if notable differences exist between animals and humans.

The first section of this document focuses on a single human acute oral exposure study in which humans were intentionally dosed with aldicarb. This beginning section will focus on the human study in regards to the single chemical risk assessment. The human data from this study are compared with animal data from the available aldicarb animal studies, and recommendations for endpoint selection are then presented based on the most appropriate studies and uncertainty factors. All of the studies are listed in summary form, followed by weight of evidence discussion for endpoint selection. Although there is another ( 1971) human study on aldicarb [ MRID 00101911], it has not been considered here. The 1971 study was flawed by the absence of a control group or a means of " blinding".

In summary, the aldicarb team for the single chemical risk assessment recommends that the rat subchronic neurotoxicity study [ MRID 43829602] and the rat acute neurotoxicity study ( MRID 45068601; Moser) be used as co critical studies for endpoint selection. The results of the acute oral human study [ MRID 42373001] suggest that animals and humans have similar toxic responses to aldicarb allowing reduction of the interspecies safety factor to 3X. A factor of 3X was retained for extrapolation from rats to humans because of the limitations of the human study as discussed in detail later in this document. The recommended endpoint selection is summarized in Table 3, column 4, together with two other possible options for endpoint selection in column 2 ( use of human study) and column 3 ( use of animal data without considering human data). For consistency, column 5 of Table 3 also lists the human RBC BMDL10 as the point of departure.

The last section of this document provides the rationale for incorporation of the human toxicity study into the N methyl carbamate pesticide ( NMC) preliminary cumulative risk assessment. Brain ChE data from acute rat toxicity studies are relied on by the Agency to provide the basis for potency determination, therefore, the Agency must consider interspecies extrapolation ( i. e., animal to human) in its cumulative risk assessment. The human study provides RBC ChE data for comparison to the available RBC and brain ChE rat data. The BMD and BMDL estimates for the rat and human data suggest similar ChE responses to aldicarb ( Table 4). Alternative approaches and the resulting uncertainties surrounding the interspecies factors are summarized and presented in Table 5. Page 3 of 19 For the cumulative risk assessment, the Agency recommends the use of the RBC BMD10 ratios of rat and human for a 2X interspecies extrapolation factor for aldicarb.

Toxicity Studies   Single Dose Oral Studies:

A. Human In a single oral dose human study with aldicarb ( MRID 42373001), following an overnight fast, subjects were dosed with aldicarb or placebo in orange juice at breakfast [ consumed over 15 30 minutes]. Cholinesterase [ ChE] activity [ plasma and RBC] was monitored hourly for the first 6 hours post dose and at 24 hours. Study design and number of subjects/ dose are provided in Table 1.

The NOAEL for males for RBC and plasma ChEI and clinical signs is 0.01 mg/ kg. The LOAEL is 0.025 mg/ kg based on sweating, plasma [ 36%] and RBC [ 12%] ChEI at 0.025 mg/ kg in males. Females were not tested at 0.01 mg/ kg, however, plasma ChEI was 50% and RBC ChEI was 20% at 0.025 mg/ kg. Although mean ChEI was different between males and females at the two mid doses, the standard error of the means of ChEI in females was greater than the standard error of the means in males. The duration of ChEI was longer in males [ at 0.050 mg/ kg: plasma ( males 1 21 hours) vs ( females 1 4 hours); RBC ( males 1 6 hours) vs ( females 1 4 hours)] than in females. Additionally, females did not display clinical signs at either dose. Both sexes show effects [ ChEI] at 0.025 mg/ kg [% inhibition listed above] and at 0.05 mg/ kg [ plasma ( males 52%/ females 68%); RBC ( males 29%/ females 36%)]. Because of uncertainty surrounding the lack of females at the lowest dose, the lowest dose tested [ 0.01 mg/ kg] is not considered an overall NOAEL for the study in the current assessment [ was considered the NOAEL in original DER].

Table 1: Summary of Dosing Regimen for Single Dose Human Oral Toxicity Study for Aldicarb There were a total of 38 men and 9 women, with 6 men/ 5 women participating in two sessions [ one placebo session and one aldicarb session]. The study consisted of several phases/ sessions such that all subjects were not dosed during the same time frame. However, there were a total of 4 females at each dose level and 4 8 males at each dose level. Page 4 of 19 Phase/ Session Placebo 0.01 mg/ kg 0.025 mg/ kg 0.05 mg/ kg 0.075 mg/ kg a 3   4 1   I males b 5     3 4*

c 4 2 2 2

d 1 3 1     II males e 3 3 1 2

f 1   1 1

g 2   1 1   III females h 3   2 2

# of subjects; * one subject received a dose of 0.06 mg/ kg, due to BW error.

Strengths  Double blind study design  Use of both sexes at mid dose levels. Both sexes were dosed at 0.025 mg/ kg and 0.05 mg/ kg thus allowing comparisons between male and female subjects.

 Administration of multiple dose levels provides quality dose response information. There were four dose groups of males [ 0.01, 0.025, 0.05, 0.075 mg/ kg] and two dose groups of females [ 0.025 and 0.05 mg/ kg]. For example, RBC ChE inhibition in males ranges from little to no inhibition at 0.01 mg/ kg to 38% at 0.075 mg/ kg.

 Blood sampling at multiple time points. Cholinesterase activity was monitored at 1, 2, 3, 4, 5, 6, and 24 hours post dose in the human study. These data provide information regarding time to recovery.

Weaknesses  Females only tested at mid doses. Females were dosed only at two dose levels compared to 4 dose levels for males; importantly females were not tested at the lowest dose ( 0.01 mg/ kg). As shown in Table 2 below, greater mean plasma and RBC ChE inhibition occurred in females at 0.05 mg/ kg compared to male subjects. The variance surrounding the mean in females was greater, however, than the variance in males. Additionally, the recovery data from samples taken every hour indicate the time of peak effect likely occurred prior to the 1 hour sampling event. Thus, the difference in ChEI observed in males and females may be due to a combination of factors of variance and timing of peak effect. Furthermore, the lack of dose response information for females at the low dose ( 0.01 mg/ kg) provides additional uncertainty for this study. Page 5 of 19  Blood sampling. The first measurement of cholinesterase activity post dose was at one hour, which may have been after the peak effect time. Clinical signs along with cholinesterase inhibition have been observed in rats as early as 0.5 hour and 0.75 hours, respectively.

 ChEI methodology. Because ChE inhibition recovers within 24 hours following exposure to N methyl carbamates, the laboratory protocol used to measure ChE inhibition is an important component of evaluating ChE inhibition data for Nmethyl carbamates. Specifically, under certain conditions recovery can occur prior to analysis and thus underestimating actual ChE inhibition. In the case of the aldicarb human study, some details surrounding the protocol for the modified Ellman were provided. These details suggest that samples were diluted to some degree. It is unknown the degree to which this may have underestimated ChE inhibition. A modified Ellman assay was also used in the guideline acute and subchronic neurotoxicity studies in rats. As noted below and in Table 2, results using a radiometric method ( preferred over Ellman) provided more inhibition at common dose levels.

B. Animals 1. In an acute [ guideline] neurotoxicity study in rats ( MRID 43442301), oral doses of 0, 0.05, 0.1, or 0.5 mg/ kg of aldicarb were administered via gavage [ vehicle water] to both sexes of young adult SD rats [ 5/ sex/ group]. Blood and brain ChE determination were made at estimated time of peak effect ( 0.75 hours) and 8 hours post dosing. Dose related increase in the inhibition of whole blood [ at 0.05 mg/ kg: males no change from pre test; females 23% inhibition from pretest value], RBC [ at 0.05 mg/ kg: males no inhibition; females 10% inhibition from pre test value], and plasma [ at 0.05 mg/ kg: males 56%; females 64%] cholinesterase activities was observed at 0.75 hours after dosing [ estimated time of peak effect], although statistical significance was not always attained at the lower dose levels. Examination of the standard deviation of the means for blood ChE measurements, especially RBC, revealed greater variability in females than males. At termination, brain cholinesterase activity was decreased significantly [ males 45%/ females 50% of control value] at 0.5 mg/ kg [ highest dose tested]. In general, mean ChE inhibition was greater in females than males, especially at the higher dose levels. At 0.5 mg/ kg, clinical signs of ChEI [ at 0.5 hours post dose: tremors, lacrimation, salivation, increased respiration, decreased body temperature, arousal, activity, reactivity, fore/ hind limb grip strength] and decreased motor activity [ 1 hour post dose] were observed. At 0.1 mg/ kg, there was decreased fore limb grip strength in females only. Recovery occurred by 8 hours after dosing. Time course of these effects were not measured in this study. The risk assessment team concludes that 0.05 mg/ kg can be considered the LOAEL for the guideline acute study. This is an acceptable guideline study.

Strengths:  Sufficient number of animals used [ 5 animals/ sex/ dose]  Both sexes tested at all dose levels Page 6 of 19  Concurrent control  3 dose levels provided quality dose response information  ChEI and clinical signs measured at estimated peak effect time ( 0.75 hours) and 8 hours postdosing Weaknesses:  Ellman method [ modified] used; a radiometric method provides a more appropriate method for measuring cholinesterase inhibition because the factors that promote reversibility are minimized.  No time course data of ChE recovery or clinical signs 2. In an acute [ non guideline] neurotoxicity study ( MRID 45068601; Moser), adult and young ( pre weanling; PND 17) Long Evans rats [ 4/ sex/ group] were directly dosed with aldicarb via gavage [ vehicle corn oil] at dose levels of 0, 0.05, 0.1, 0.2, or 0.3 mg/ kg. At 0.05 mg/ kg ( lowest dose tested) in PND 17 rats, whole blood ChE inhibition was 75% 81% and brain ChE inhibition was 24 28 %; in adult rats, whole blood ChE inhibition was 84% and brain inhibition was 10 12%. No difference between the sexes was identified in either age group. This study shows an increase in sensitivity only in terms of percent brain ChE inhibition for PND 17 rats in comparison to adults. Both age groups had greater than 75% whole blood ChE inhibition at all dose levels. The LOAEL is 0.05 mg/ kg. This study was classified acceptable/ non guideline.

Strengths:  Both sexes at all doses  Concurrent control group  4 treatment dose levels provided quality dose response information  4 animals/ sex/ group  Radiometric method used.  Adult and juvenile animals evaluated providing information on age related sensitivity Weaknesses:  Fewer animals per group than used in guideline study  Significant inhibition observed at all dose levels (> 75% whole blood inhibition at lowest dose level in adult and juvenile animals.)

! Repeated Dose Oral Studies A. Human There is no repeated dose study on aldicarb in humans. However, based on the reversibility of the effects observed within 24 hours following acute oral exposure of human and following oral exposures of varying lengths to rats, toxicity Page 7 of 19 observed in the acute oral human study is considered representative of all exposure durations.

B. Animal 1. Subchronic neurotoxicity ( 90 day rat). In a subchronic neurotoxicity study ( MRID 43829602), Crl: CDR( SD) BR rats were dosed via gavage with 0 [ water vehicle], 0.05, 0.20, or 0.40 mg/ kg/ day of aldicarb ( tech., 98.9%) for at least 13 weeks. Twelve animals/ sex/ group were selected for functional observational battery ( FOB) [ pre study and at weeks 4, 8, 13 at approximately 0.5 to 1 hour post dose] and motor activity ( MA) testing, and 15 animals/ sex/ group were selected for serial acetylcholinesterase ( ChE) analyses [ pre study and at weeks 4, 8, 13 at approximately 0.75 hour post dose]. Six rats/ sex/ dose were anesthetized, perfused, and sacrificed for histopathology. CNS sections were embedded in paraffin, while peripheral nerves and spinal ganglia were embedded in plastic.

No treatment related deaths occurred. Body weight and body weight gains were decreased in the high dose males, as was food consumption/ efficiency, but these parameters were comparable among the females groups. Dose related tremors and salivation were observed in both sexes in the mid and high dose group. Treatment related clinical signs of cholinesterase inhibition/ neurotoxicity [ home cage and arena tremors, pinpoint pupils, decreased tail pinch response, decreased hindlimb/ forelimb grip strength, increased tail flick latency times] were observed in both sexes at various time points during the study, with the severity increasing with dose, and there was some evidence that females were more sensitive. Additionally, motor activity was decreased in both sexes at the midand high dose levels throughout the study. Ophthalmoscopic examination [ performed at study termination and not at peak effect time], gross and histopathological evaluations did not show any treatment related effects.

There was a dose related inhibition in plasma [ 61% 90%], whole blood [ 42% 87%], and RBC [ 24% 70%] ChE in both sexes and at all doses. Statistical significance was not attained for plasma ChEI for the low dose rats of either sex. Whole brain ChE inhibition was observed in both sexes at the mid and highdose levels, and in females at the low dose, as well as in cerebellum in low dose females. The level of whole brain ChE inhibition at the mid [ males 26% 42%; females 33% 46%] and high [ males 58% 64%; females 57% 68%] dose appear to show some increase across weeks 4 13. Ophthalmoscopic examination and gross and histopathological evaluations did not reveal significant aldicarb related changes. An increased incidence of slight axonal degeneration in the sciatic nerve, described as affecting only individual nerve fibers, were found in 3 high dose males vs one control rat, and 2 high dose females vs one control rat, but these findings lacked statistical significance. Page 8 of 19 The LOAEL is 0.05 mg/ kg/ day, based on the FOB findings ( e. g., pinpoint pupils) and ChE inhibition in blood and brain. The NOAEL is < 0.05 mg/ kg/ day.

In Summary, the available data on the rat indicate a peak effect within an hour of dosing, and the inhibition recovers within 24 hours. Although this study, in which several time periods were investigated, shows an apparent increase in percent ChEI in some sections of the brain at the high dose levels, there was no decrease in the NOAEL or LOAEL for ChEI with time. For aldicarb RBC and/ or whole blood ChE inhibition are the most sensitive endpoints. In all available studies RBC and/ or whole blood ChE inhibition do not increase with repeated exposures.

2. Chronic and subchronic ( dog). In a 1 year dog feeding study ( MRID 40695901), groups of 5 beagle dogs/ sex/ dose were administered aldicarb technical in the diet daily for 52 weeks at 0, 1, 2, 5, and 10 ppm ( 0, 0.028, 0.056, 0.13, and 0.25 mg/ kg day). Blood ( plasma and red blood cell) cholinesterase determinations were made 3 times prior to exposure and during weeks 5, 13, 26, and 52, two hours after the 2 hour feeding period. Brain measures were made at study termination.

In the one year study, no effects were seen on mortality, body weight gain, food consumption, clinical signs, clinical chemistry, hematology, urinalysis, organ weights, ophthalmology, gross pathology or histopathology. At the 3 highest dose levels, dogs showed significant dose related inhibition in plasma ChE activity in both sexes. At the lowest dose, there was significant plasma cholinesterase inhibition in males ( 18 26%). Significant dose related decreases in RBC Cholinesterase were seen at the 2 highest doses in males and the highest dose in females. Brain cholinesterase was significantly inhibited only at the high dose in males ( 22%). Based on plasma ChEI, a NOAEL for ChE inhibition in the study was not established in the one year study [ LOAEL of 0.028 mg/ kg/ day].

In a subsequent subchronic study ( MRID 41919901), 6 beagle dogs/ sex/ dose were administered aldicarb via the diet at 0, 0.35, 0.7, and 2 ppm [ 0, 0.01, 0.02, and 0.06 mg/ kg/ day]. Plasma and RBC cholinesterase determinations were made at  3,  2,  1 weeks prior to dosing and at 2 and 5 weeks, two hours after a limited 2 hour feeding period.

In this subsequent 5 week study in dogs, a NOAEL for plasma and RBC cholinesterase activity inhibition was established at 0.020 mg/ kg/ day; LOAEL is 0.06 mg/ kg.

  Benchmark Dose ( BMD) Analysis A dose response analysis and estimation of the BMD10s were performed using the whole blood ChEI data from the two acute animal studies [ guideline and Page 9 of 19 Moser], as well as the whole blood ChEI data from the guideline subchronic neurotoxicity study. An exponential model similar to that used in the OP Cumulative Risk Assessment and supported by the FIFRA SAP was used. The BMD10s for whole blood ranged from 0.0031 to 0.012 mg/ kg in adult animals and 0.0038 to 0.0073 mg/ kg in juvenile animals. The BMD10s for brain ranged from 0.024 to 0.031 mg/ kg in adult animals and 0.014 to 0.020 mg/ kg in juvenile animals. Lack of dose response data in whole blood ( all doses > 75% inhibition) provide less confidence in the BMD10s compared to those calculated for brain ChE inhibition. Ratios of the BMD10s for brain ChE inhibition between juvenile and adult animals suggest that juvenile animals are 2X more sensitive than adult rats.

Endpoint Selection.

Acute RfD. The risk assessment team concludes that the similarity of response between humans and rats following acute oral exposure allows for the use of both sets of data in considering toxicity endpoint selection and uncertainty factors ( grey column in Table 3). Table 2 provides ChE inhibition observed in rats and humans at a dose level common to several studies, 0.05 mg/ kg. As shown in Table 2, there is remarkable similarity between the human study and rat studies ( subchronic and acute), which used a modified Ellman technique ( subchronic rat, acute rat, acute human). The Moser study, which considered both adult and juvenile animals, measured ChE inhibition using a preferred methodology, the radiometric method. It is also important to note that the Moser study used corn oil as the gavage vehicle, which may promote more absorption compared to water used as the gavage vehicle in the subchronic and acute rat studies performed by the pesticide registrant.

Table 2. Comparison of % ChEI at 0.05 mg/ kg compartment/ sex/ stu dy subchronic rat [ week 4] rat acute human acute rat acute [ Moser]

males RBC 32%  29% not measured plasma 61% 44% 55% not measured whole blood 42%  N/ A 84%

females RBC 24%  36% not measured plasma 65% 36% 68% not measured whole blood 47% 23% N/ A 81%

The risk assessment team considered the rat subchronic neurotoxicity study and the non guideline acute neurotoxicity study ( Moser) to be co critical for Page 10 of 19 assessment of the acute exposure scenarios. Due to the fact that reversibility of ChEI occurs within 24 hours following aldicarb exposure, the use of this subchronic neurotoxicity study in rats for endpoint selection is considered appropriate ( repeated dosing is considered a series of acute exposures). The cholinesterase inhibition in the acute human study and rat subchronic study were comparable at the 0.05 mg/ kg dose level. As noted above for the human study, there are uncertainties regarding the lack of female subjects at the lowest dose ( 0.01 mg/ kg), larger standard errors of the means for female ChEI, and no measurement at the estimated time of peak effect (< 1 hour). Mean female ChE inhibition was greater at the 0.025 and 0.05 mg/ kg levels 1 hour post dosing compared to male subjects. Although no rat studies have established a NOAEL for brain, RBC and/ or whole blood ChE inhibition, the database of rat studies includes studies where animals of both sexes were tested at each dose level, studies comparing adult and juvenile animals, measurement of clinical signs at < 1 hour, and evaluation using both Ellman and radiometric methods. Thus, the rat database provides a solid basis for developing the point of departure for aldicarb. The similarity in response between humans and rats at 0.05 mg/ kg ( Table 2), however, allows for the reduction of the interspecies factor [ Table 3, Column 4] from 10X to 3X. A factor of 3X was retained for extrapolation from rats to humans because of the limitations of the human study. These limitations include:

! Use of the Ellman method for human ChEI measurements rather than the more sensitive radiometric method which was used in the co critical Moser study;

! Human females were not dosed at the lowest dose level, and females may be slightly more sensitive than males ( either in time of peak effect, time of recovery, or magnitude of inhibition); therefore, an adequate comparison of human and rat females could not be made;

An additional 10X uncertainty factor is needed to account for extrapolating from a LOAEL to NOAEL. It is notable that greater than 75% whole blood ChEI was observed in both age groups at the LOAEL. The 10X LOAEL to NOAEL factor is supported by the estimated whole blood rat BMD10s [ 0.003 0.012]. In addition, female human subjects at the lowest dose ( 0.025 mg/ kg) had 20% RBC inhibition. Given these uncertainties, an additional 10X is appropriate to extrapolate from a LOAEL of 0.05 mg/ kg to NOAEL of 0.005 mg/ kg. Therefore, a total uncertainty factor of 300 ( 10X for intraspecies variations, 3X for interspecies differences, and 10X LOAEL to NOAEL) is appropriate.

FQPA Safety Factor Considerations For the recommended endpoints selected from animal studies, a Special Hazard Based FQPA safety factor is not needed. As shown by the BMD analysis, juvenile animals are approximately 2X more sensitive than adult rats. Using the recommended approach, this sensitivity is accounted for in the point of departure of 0.005 mg/ kg/ day as the BMDs for the young were estimated to be 0.0038 Page 11 of 19 0.0073mg/ kg/ day for whole blood ChE inhibition. The extrapolated NOAEL of 0.005 mg/ kg/ day incorporates this potential sensitivity since the point of departure risks are not likely to be under estimated based on the NOAEL = 0.005 mg/ kg/ day. The database for aldicarb is complete, including both rat [ MRID 41004501] and rabbit [ MRID 00132668] developmental toxicity studies, a rat 2 generation reproduction study [ MRID 42148401], acute and subchronic rat neurotoxicity studies, a rat developmental neurotoxicity study [ MRID43829601], as well as a special acute neurotoxicity study ( Moser). Therefore, an FQPA database UF is also not required. There is no evidence of increased sensitivity in any of the guideline studies.

Alternatively, if the endpoint from the human study were to be selected for risk assessment there are no juvenile data from the human study to address the FQPA safety factor. However, the acute neurotoxicity study ( Moser) in rats indicates the magnitude of the brain ChEI in the PND 17 pups was only 2X greater than that of the adult rat. There is currently no information to suggest that the difference in rat brain ChEI would be different than human brain ChEI. Therefore, the acute neurotoxicity study supports a FQPA safety factor of 2X [ see Table 3; column 2].

NOTE: There are no residential uses of aldicarb.

Short and intermediate term residential & occupational exposure.

Based on the fact that reversibility of effects within 24 hours is seen in both the human and animal studies and on the fact that dosing in the subchronic neurotoxicity study in rats and special acute neurotoxicity study are considered a series of acute exposures, the same co critical studies are considered appropriate for endpoint selection.

Chronic RfD and long term residential & occupational exposure.

The risk assessment team recommends the use of the same co critical studies for establishing a chronic RfD and to assess long term occupational or residential risk. However, the team has determined that a chronic risk assessment is not needed, since risks resulting from aldicarb exposure are better described as a series of acute risks.

Furthermore, any chronic risks would necessarily be lower than those estimated for acute exposure since long term average exposure levels rather than daily high end exposure estimates would be used to calculate chronic risks.

Short, intermediate and long term inhalation exposure. same as above Page 12 of 19 Table 3. Comparison of Endpoint Selection Possibilities Parameter Human study1 Rat study2 Rat ( human) 3 ( recommended) Human BMDL10 4 LOAEL 0.01 mg/ kg 0.05 mg/ kg 0.05 mg/ kg 0.013 mg/ kg UF LOAEL to NOAEL 3X 10X 10X 1X NOAEL 0.0033 mg/ kg 0.005 mg/ kg 0.005 mg/ kg 0.013 mg/ kg UF ( intraspecies) 10X 10X 10X 10X UF ( interspecies) 1X 10X 3X 1X FQPA SF 2X 1X 1X 2X acute RfD 0.00033 mg/ kg 0.00005 mg/ kg 0.00017 mg/ kg 0.0013 mg/ kg acute PAD 0.00017 mg/ kg 0.00005 mg/ kg 0.00017 mg/ kg 0.00065 mg/ kg chronic RfD 0.00033 mg/ kg/ day 0.00005 mg/ kg/ day 0.00017 mg/ kg/ day 0.0013 mg/ kg/ day chronic PAD 0.00017 mg/ kg/ day 0.00005 mg/ kg/ day 0.00017 mg/ kg/ day 0.00065 mg/ kg/ day endpoint RBC/ plasma ChEI whole blood/ brain ChEI whole blood/ brain ChEI RBC ChEI 1Human study = Endpoints and Points of Departure using human study 2Rat Study = Endpoints and Points of Departure using animal studies without consideration of human study 3Rat ( human) = Endpoints and Points of Departure using animal data for endpoint selection, comparing animal data to human data to reduce interspecies safety factor, both considered as part of weight ofevidence determination 4Human BMDL= Endpoint and Point of Departure using RBC ChEI human data for the BMD analysis   Part B of Weight of Evidence: Integration of Aldicarb into the Preliminary N Methyl Carbamate ( NMC) Cumulative Risk Assessment 1. Background:

The Food Quality Protection Act ( FQPA) was passed by Congress in 1996. The FQPA made key changes to the approaches used by EPA to assess pesticide chemicals. One of these changes was the requirement to consider cumulative risk to those pesticides which act by a common mechanism of toxicity. Pesticides are determined to have a " common mechanism of toxicity" if they act the same way in the body that is, the same toxic effect occurs in the same organ or tissue by essentially the same sequence of major biochemical events. OPP established the N methyl carbamate pesticides ( NMCs) as a common mechanism group and in accordance with FQPA has developed a preliminary cumulative risk assessment for this group of pesticides ( USEPA, 2005). Aldicarb is a member of the NMC common mechanism group.

OPP has developed a guidance document for developing cumulative risk assessments under FQPA ( USEPA, 2002). This guidance indicates that when developing a multi chemical hazard assessment, comparison of toxic potency Page 13 of 19 should be made using a uniform basis of comparison, by using to the extent possible a common response derived from a comparable measurement methodology, species, and sex for all the exposure routes of interest. In the preliminary cumulative risk assessment, the Agency considered RBC and brain ChE inhibition as potential endpoints. Plasma cholinesterase data were not considered since the primary enzyme in plasma is butylcholinesterase and not acetylcholinesterase. Ultimately, brain ChE data from acute rat toxicity studies measured at or near the time of peak effect have been used by EPA to estimate a relative potency factor ( RPF) and to develop the points of departure ( PoD) for extrapolating cumulative risk. For instance, the brain BMD10 has been used to calculate the RPF while the brain BMDL10 establishes the PoD in the preliminary cumulative risk assessment. Brain data have been selected over RBC data as brain ChE inhibition represents a direct measure of the target tissue ( as opposed to blood data which is considered a surrogate measure) and brain ChE inhibition data tend to have less variation and thus confer less uncertainty on cumulative risk estimates.

Because data from rat studies provide the basis for potency determination, the Agency must consider interspecies extrapolation ( i. e., animal to human) in its cumulative risk assessment. As such, human data may be used by the Agency to inform the pesticide specific interspecies extrapolation. In the specific case of aldicarb, MRID 42373001 is available.

2. Aldicarb Human Study Summary:

The aldicarb human study involved both male and female volunteers, with males only at the lowest dose ( 0.01 mg/ kg) and highest dose ( 0.075 mg/ kg). Blood samples were taken for ChE activity every hour, beginning at 1 hour post dosing until 6 hours and then at 24 hours. The multiple sampling over time provides the progression of enzyme inhibition along with enzyme reactivation. Peak ChE inhibition, however, likely occurred prior to the first sampling event at 1 hour.

The human toxicity study for aldicarb does not provide brain ChE data, for obvious reasons, but does provide ChE data for both males and females. The blood ChE activity ( plasma and RBC) provided in the human study is considered appropriate surrogate measures of potential effects on peripheral nervous system ( PNS) acetylcholinesterase ( AChE) activity, and of potential effects on the central nervous system ( CNS) when brain ChE data are lacking ( USEPA 2000). AChE is the target enzyme for the cumulative risk assessment and is the primary form of ChE found in RBCs. Butylcholinesterase ( BChE), on the other hand, is the primary for of ChE found in plasma. BChE is considered a measure of exposure but has not been shown to be of toxicological significance. RBC ChE data, therefore, is being utilized by the Agency to inform the pesticidespecific interspecies extrapolation. Page 14 of 19 The measured RBC ChE activity from the human study is adequate for estimation of BMD and BMDL estimates. The RBC ChE data from the aldicarb human study was utilized in the model in the same manner as the acute rat data ( brain and RBC) that are available for the NMCs of the cumulative hazard assessment ( USEPA 2005). The BMD10 and BMDL10 estimates for both rat ( RBC, brain) and human ( RBC) are included in Table 4 below. It should be noted that the samples collected at the hour time point only provide a brief look at ChE inhibition at that specific moment in time. Uncertainties still exist regarding the timing and magnitude of peak ChE inhibition in the male versus the female prior to 1 hour.

Based on the FIFRA SAP ( 2005) approval of statistical analyses for the BMD model, the single RBC BMD estimate for aldicarb indicates similar ChE activity in males and females ( 0.02 mg/ kg, M and F). Although the mean values for the RBC ChE in females of the study were greater than males at the two mid doses, the BMD analysis of the standard error of the means indicate no differences between sexes.

ChE inhibition from the two compartments also appears to be similar ( brain and RBC). For example, rat BMD10 for rat brain ( 0.05 mg/ kg F, 0.06 mg/ kg M) is similar to the BMD10 for rat RBC ( 0.03 mg/ kg, M and F). As such, the estimate from the aldicarb human study provides useful information into the sensitivity of RBC ChE inhibition of rats compared to humans.

Table 4. Oral BMD10s and BMDL10s Generated from Rat ChE ( RBC, brain) and Human ChE ( RBC) Data for Aldicarb.

Rat Human Brain RBC RBC Chemical BMD10 ( mg/ kg) BMDL10 ( mg/ kg) BMD10 ( mg/ kg) BMDL10 ( mg/ kg) BMD10 ( mg/ kg) BMDL10 ( mg/ kg) Aldicarb F= 0.05 M= 0.06 F= 0.03 M= 0.03 0.03 0.02 0.02 0.01 BMD estimates are presented as a single estimate when there are no differences between sexes. Human RBC data obtained from MRID 42373001 Rat brain and RBC data obtained from MRIDs 43442302, 43442305, 43829601, 43829602, 45068601.

3. Discussion Several studies for aldicarb are available that provide quality dose response and ChE inhibition data from both the rat and human. For purposes of the cumulative risk assessment, the difficulty lies in extrapolating information across compartments ( blood brain). The preliminary NMC cumulative risk assessment relies on rat brain ChE data for the relative potency factors ( RPFs) and points of departure ( PoDs). The FIFRA SAP supported the Agency's use of brain ChE data in August 2005 ( FIFRA SAP 2005). Page 15 of 19 By outlining the available data for aldicarb it is apparent that a couple of approaches are available for application of the interspecies extrapolation factor for the preliminary cumulative risk assessment. Table 5 below highlights for aldicarb the potential approach, BMD10 ratio, interspecies factor and confidence level, and the pros, cons, or uncertainties surrounding these options for interspecies calculation. The first approach is the use of the Agency's default 10X factor for extrapolation of animal to human. The second approach is the ratio of RBC BMD10 rat ( both sexes) to RBC BMD10 human ( both sexes). The estimated factor and confidence interval are based on the modeling of both rat and human RBC data. The uncertainties surrounding both of these approaches are highlighted in the table below. It should also be noted that an additional approach is the ratio of rat brain BMD10 to human RBC BMD10. This option would compare brain data relied on in the cumulative risk assessment with available RBC data from the human studies. This ratio does not compare ChE data from the same compartment and, therefore, is less appropriate for interspecies extrapolation for aldicarb.

At the present time, the BMD analysis for aldicarb indicates females and males are similar in sensitivity to ChE inhibition at low doses, which is the appropriate measurement for the cumulative risk assessment. Other evidence to consider is the mean and variance of ChE inhibition of females and males from the human study. Based strictly on mean percent ChE inhibition at the 1 hour time point, females had greater ChE inhibition than males. The variance of the ChE mean, however, was also greater in females than in males. Additionally, the timecourse data indicate the time of peak effect is likely less than 1 hour. There was no measurement prior to the one hour time point in the study for the elucidation of time of peak effect in either males or females. Recovery ChE data also indicate males ( 1 6 hours) are slower to recover than females ( 1 4 hours). As for rat data, there are conflicting ChE inhibition data. One acute neurotoxicity study ( Moser) indicated no sex differences in ChE inhibition in juvenile rats. However, another acute neurotoxicity study ( MRID 43442301) indicated greater ChE inhibition of adult females than adult males, but only at the higher dose levels.

As for compartment differences, given the similarity between brain and RBC ChE in rats, the Agency is not aware of any biological or physiological reason that human brain ChE would be more sensitive than the rat brain. The Agency, therefore, proposes to use the RBC BMD10 ratios of rats and human for a resulting interspecies extrapolation factor 2X for aldicarb ( CI 1.1 3.6). This interspecies extrapolation factor would be in addition to the other uncertainty factors for the cumulative risk assessment that includes intraspecies variability ( human variability) and FQPA. The acute neurotoxicity study ( Moser) will likely be considered for defining the FQPA safety factor. Page 16 of 19 Table 5. Comparison of the Alternative Choices and the Resulting Uncertainties Surrounding the Refinement of the Interspecies Extrapolation Factor for Aldicarb in the NMC Cumulative Risk Assessment Option of Refinement for Interspecies Factor Resulting Interspecies Factor Ratio Confidence Interval Pros Cons or Uncertainties 1. Default Factor for Risk Assessment 10X NA 1. Standard uncertainty factor for interspecies extrapolation. 2. Accounts for uncertainty regarding lack of female data at low dose. 3. Accounts for uncertainty regarding lack of ChE brain data in humans. 1. Ratio of RBC BMDs indicate 2X.

2. Ratio of RBC BMD10 rat vs. human RBC BMD10 2X1 1.1 to 3.6 1. BMD10 ratio is based on the same compartment ( RBC) in rat ( both sexes) and human ( male only at low dose). 2. Inhibition of RBC ChE in rats is similar between sexes. 1. Uncertainty remains for lack of brain ChE inhibition in humans. 2. Uncertainty remains for lack of female data at low dose.

1The resulting 2X interspecies factor based on the innovative BMD approach is concordant with the 3X interspecies factor of the single chemical assessment, which was based on the traditional HED approach of establishing an interspecies factor.

FIFRA SAP ( 2005). Meeting Minutes of the FIFRA Scientific Advisory Panel Held August 23 26, 2005. SAP Minutes No. 2005 04. Preliminary N Methyl Carbamate Cumulative Risk Assessment. October 13, 2005.

USEPA ( 2000). " The Use of Data on Cholinesterase Inhibition for Risk Assessments of Organophosphorous and Carbamate Pesticides"; August 18, 2000. Available: http:// www. epa. gov/ pesticides/ trac/ science/ cholin. pdf USEPA ( 2002). " Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity." January 14, 2002. ( 67 FR 2210; January 16, 2002) http:// www. epa. gov/ oppfead1/ trac/ science/# common USEPA ( 2005). Preliminary N Methyl Carbamate Cumulative Risk Assessment. Office of Pesticide Programs, U. S. Environmental Protection Agency. Washington, DC. http:// www. epa. gov/ scipoly/ sap/ index. htm# sept Page 17 of 19 APPENDIX I Aldicarb Toxicology Endpoint Selection.

Exposure Scenario Dose Used in Risk Assessment, UF1 Hazard Based FQPA SF and Endpoint for Risk Assessment Study and Toxicological Effects DIETARY EXPOSURES Acute Dietary: General US Population [ MRID No. 43829602, 45068601, & 42373001] LOAEL= 0.05 mg/ kg/ day UF= 300 Acute RfD= 0.00017 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD FQPA SF = 0.00017 mg/ kg/ day Rat subchronic/ acute neurotoxicity study LOAEL= 0.05 mg/ kg/ day, based on whole blood and brain ChEI and FOB findings ( pinpoint pupils) Human study [ reduction of interspecies factor to 3x]

Chronic Dietary: General US Population [ MRID No. 43829602, 45068601, 42373001] LOAEL= 0.05 mg/ kg/ day UF= 300 Chronic RfD= 0.00017 mg/ kg/ day FQPA SF= 1X cPAD= chronic RfD FQPA SF = 0.00017 mg/ kg/ day Rat subchronic/ acute neurotoxicity study LOAEL= 0.05 mg/ kg/ day, based on whole blood and brain ChEI and FOB findings ( pinpoint pupils)

Human study [ reduction of interspecies factor to 3x]

Dermal Exposures2 Short Term ( 1 30 days);

Intermediate Term ( 30 days to several months) [ MRID No. 43829602, 45068601, 42373001] Oral study LOAEL= 0.05 mg/ kg/ day Absorption Factor= 100% LOC for MOE= 3001 Rat subchronic/ acute neurotoxicity study LOAEL= 0.05 mg/ kg/ day, based on whole blood and brain ChEI and FOB findings ( pinpoint pupils)

Human study [ reduction of interspecies factor to 3x]

Inhalation Exposures2 Any Duration [ MRID No. 43829602, 45068601, 42373001] Oral study LOAEL= 0.05 mg/ kg/ day Absorption Factor= 100% LOC for MOE= 3001 Rat subchronic/ acute neurotoxicity study LOAEL= 0.05 mg/ kg/ day, based on whole blood and brain ChEI and FOB findings ( pinpoint pupils) Human study [ reduction of interspecies factor to 3x]

1 The combined UF of 300 includes 3X for interspecies extrapolation, 10X is for intraspecies variability, and a database UF of 10X for extrapolation from the LOAEL to the NOAEL.

2 Appropriate route to route extrapolation should be performed for these risk assessments. For both dermal and inhalation risks, a 100% absorption factor should be used to convert relevant exposure estimates to equivalent oral doses and compared to the oral LOAEL. Page 18 of 19 APPENDIX II Guideline No./ Study Type MRID No. ( year)/ Classification Results 870.3150 90 Day oral toxicity in non rodents ( dogs) 2 hours post dose 41919901 ( 1991) Acceptable NOAEL = 0.02 mg/ kg/ day LOAEL = 0.06 mg/ kg/ day based on plasma, RBC Cholinesterase Inhibition in male and female dogs 870.3700a Prenatal developmental in rodents ( rats) 41004501 ( 1988) Acceptable Maternal NOAEL = 0.125 mg/ kg/ day LOAEL = 0.25 mg/ kg/ day based on decreased body weight gain and food consumption. Developmental NOAEL = 0.125 mg/ kg/ day LOAEL = 0.25 mg/ kg/ day based on ecchymosis of the trunk.

870.3700b Prenatal developmental in non rodents ( rabbits) 00132668 ( 1983) Acceptable Maternal NOAEL = 0.1 mg/ kg/ day LOAEL = 0.25 mg/ kg/ day based on decreased body weight, pale kidneys, hydroceles on the oviducts. Developmental NOAEL = > 0.5 mg/ kg/ day 870.3800 Reproduction and fertility effects at termination 42148401 ( 1991) Acceptable Parental/ Systemic NOAEL = 0.4 mg/ kg/ day LOAEL = 0.7 0.9 mg/ kg/ day based on decreased body weight gains and RBC ChEI (&); plasma ChEI (%). Reproductive NOAEL = 0.7 0.9 mg/ kg/ day LOAEL = 1.4 1.7 mg/ kg/ day based on decreased viability and body weights, and signs of debilitation.

870.4100a Chronic toxicity rodents am sample 43045401 ( 1993) Acceptable NOAEL = 0.047 mg/ kg/ day LOAEL = 0.47 mg/ kg/ day based on plasma, RBC, cholinesterase inhibition (%).

870.4100b Chronic toxicity dogs beagle 2 hours after feeding 40695901, 42191501 ( 1988) Acceptable NOAEL < 0.028 mg/ kg/ day LOAEL = 0.028 mg/ kg/ day based on plasma ChEI.

870.6200a Acute neurotoxicity screening battery Sprague Dawley Crl: CD( SD) BR rat peak effect time 0.75 hour 43442301 ( 1994) Acceptable NOAEL = 0.05 mg/ kg/ day LOAEL = 0.1 mg/ kg/ day based on behavioral changes; plasma ChEI. at 0.05 mg/ kg 870.6200b Subchronic neurotoxicity screening battery Sprague Dawley Crl: CD( SD) BR rat peak effect time 0.75 hour 43829602 ( 1995) Acceptable NOAEL < 0.05 mg/ kg/ day LOAEL = 0.05 mg/ kg/ day based on pinpoint pupils and blood and brain ChEI. Page 19 of 19 Guideline No./ Study Type MRID No. ( year)/ Classification Results 870.6300 Developmental neurotoxicity Sprague Dawley Crl: CD( SD) BR rat ChE activity monitored 2 hours post dose 43829601 ( 1995) Acceptable Maternal NOAEL = 0.05 mg/ kg/ day LOAEL = 0.1 mg/ kg/ day based on plasma ChEI. Offspring NOAEL = 0.05 mg/ kg/ day LOAEL = 0.1 mg/ kg/ day based on reduced body weights and decreased motor activity.

Acute neurotoxicity Special studies Moser VC Long Evans rat peak effect time 1 hour 45068601 ( 1999) TAP 157 94 106 Acceptable NOAEL < 0.05 mg/ kg. PND 17 day pups 2x as sensitive as adults in brain ChEI. LOAEL = 0.05 mg/ kg pups blood (%,&), brain ChEI (%)

Acute oral  human ChE activity monitored at 1, 2, 3, 4, 5, 6, 24 hours post dose 42373001 ( 1992) Acceptable NOAEL for males 0.01 mg/ kg, based on RBC and plasma ChEI and sweating at LOAEL of 0.025 mg/ kg NOAEL not determined in females; LOAEL = 0.025 mg/ kg, based on RBC and plasma ChEI