[Federal Register: May 15, 2009 (Volume 74, Number 93)]
[Rules and Regulations]
[Page 23045-23095]
[DOCID:fr15my09-13]

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Part III

Environmental Protection Agency

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40 CFR Part 180

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Carbofuran; Final Tolerance Revocations; Final Rule

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0162; FRL-8413-3]

Carbofuran; Final Tolerance Revocations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: EPA is revoking all tolerances for carbofuran. The Agency has
determined that the risk from aggregate exposure from the use of
carbofuran does not meet the safety standard of section 408(b)(2) of
the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This final rule is effective August 13, 2009. Written
objections, requests for a hearing, or requests for a stay identified
by the docket identification (ID) number EPA-HQ-OPP-2005-0162 must be
received on or before July 14, 2009, and must be filed in accordance
with the instructions provided in 40 CFR part 178 (see also Unit I.C.
of the SUPPLEMENTARY INFORMATION).

ADDRESSES: Written objections and hearing requests, identified by the
docket ID number EPA-HQ-OPP-2005-0162, may be submitted to the Hearing
Clerk by one of the following methods:
     Mail: U.S. EPA Office of the Hearing Clerk, Mailcode 1900
L, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001.
     Delivery: U.S. EPA Office of the Hearing Clerk, 1099 14th
St., NW., Suite 350, Franklin Court, Washington, DC 20005. Deliveries
are only accepted during the Office's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Office's telephone number is<PHONE_NUMBER>.
    In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2005-0162, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is<PHONE_NUMBER>.
    Docket: All documents in the docket are listed in the docket index.
Although listed in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure 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 in the electronic docket at http://www.regulations.gov, or,
if only available in hard copy, at the OPP Regulatory Public Docket in
Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal Dr.,
Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The Docket Facility
telephone number is<PHONE_NUMBER>.
    Submitting CBI. Do not submit this information to EPA through
regulations.gov or e-mail. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as
CBI and then identify electronically within the disk or CD-ROM the
specific information that is claimed as CBI. In addition to one
complete version of the objection that includes information claimed as
CBI, a copy of the objection that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.

FOR FURTHER INFORMATION CONTACT: Jude Andreasen, Special Review and
Reregistration Division (7508P), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave, NW.,
Washington, DC 20460-0001; telephone number:<PHONE_NUMBER>; e-mail
address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does This Action Apply to Me?

    You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. To determine
whether you or your business may be affected by this action, you should
carefully examine the applicability provisions in Unit II.A. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.

B. How Can I Access Electronic Copies of This Document?

    In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://
www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.

C. What Can I Do if I Wish the Agency To Maintain a Tolerance That the
Agency Has Revoked?

    Any affected party has 60 days from the date of publication of this
order to file objections to any aspect of this order with EPA and to
request an evidentiary hearing on those objections (21 U.S.C.
346a(g)(2)). A person may raise objections without requesting a
hearing.
    The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objection (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). If a

hearing is requested, the objections must include a statement of the
factual issue(s) on which a hearing is requested, the requestor's
contentions on such issues, and a summary of any evidence relied upon
by the objector (40 CFR 178.27).
    Although any person may file an objection, the substance of the
objection must have been initially raised as an issue in comments on
the proposed rule. As explained in the July 31, 2008 proposed rule (73
FR 44864) (FRL-8378-8), EPA will treat as waived any issue not
originally raised in timely submitted comments. Accordingly, EPA will
not consider any legal or factual issue presented in objections that
was not presented by a commenter in response to the proposed rule, if
that issue could reasonably have been raised at the time of the
proposal.
    Similarly, if you fail to file an objection to an issue resolved in
the final rule within the time period specified, you will have waived
the right to challenge the final rule's resolution of that issue (40
CFR 178.30(a)). After the specified time, issues resolved in the final
rule cannot be raised again in any subsequent proceedings on this rule.
See Nader v EPA, 859 F.2d 747 (9th Cir. 1988), cert denied 490 US 1931
(1989).
    You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in 40 CFR part
178. To ensure proper receipt by EPA, you must identify docket ID
number EPA-HQ-OPP-2005-0162 in the subject line on the first page of
your submission. All requests must be in writing, and must be received
by the Hearing Clerk as required by 40 CFR part 178 on or before July
14, 2009.
    EPA will review any objections and hearing requests in accordance
with 40 CFR 178.30, and will publish its determination with respect to
each in the Federal Register. A request for a hearing will be granted
only to resolve factual disputes; objections of a purely policy or
legal nature will be resolved in the Agency's final order, and will
only be subject to judicial review pursuant to 21 U.S.C. 346a(h)(1),
(40 CFR 178.20(c) and 178.32(b)(1)). A hearing will only be held if the
Administrator determines that the material submitted shows the
following: There is a genuine and substantial issue of fact; there is a
reasonable probability that available evidence identified by the
requestor would, if established, resolve one or more of such issues in
favor of the requestor, taking into account uncontested claims to the
contrary; and resolution of the issue(s) in the manner sought by the
requestor would be adequate to justify the action requested (40 CFR
178.30).

II. Introduction

A. What Action Is the Agency Taking?

    EPA is revoking all of the existing tolerances for residues of
carbofuran. Currently, tolerances have been established on the
following crops: Alfalfa, forage; alfalfa, hay; artichoke, globe;
banana; barley, grain; barley, straw; beet, sugar roots; beet, sugar
tops; coffee bean, green; corn, forage; corn, grain (including
popcorn); corn, stover; corn, sweet, kernel plus cob; cotton,
undelinted seed; cranberry; cucumber; grape; grape raisin; grape,
raisin, waste; melon; milk; oat, grain; oat, straw; pepper; potato;
pumpkin; rice, grain; rice, straw; sorghum, forage; sorghum, grain
grain; sorghum, grain, stover; strawberry; soybean, forage; soybean,
hay; squash; sugarcane, cane; sunflower, seed; wheat, grain; wheat,
straw.
    As discussed at greater length in Unit VII., on September 29, 2008,
the sole registrant of carbofuran pesticide products, FMC Corporation
requested that EPA cancel certain registrations. Consistent with the
request, the registrant indicated that it no longer seeks to maintain
the tolerances associated with the domestic use of carbofuran on the
eliminated crops, and therefore no longer opposes the revocation of
those tolerances. No other commenter indicated any interest in
maintaining these tolerances. EPA is therefore revoking the tolerances
associated with those domestic uses on two separate grounds. The first
is that the tolerances will no longer be necessary because the
registrations for these uses have been canceled (74 FR 11551, March 18,
2009) (FRL-8403-6). The tolerances that EPA is revoking on this basis
are: Alfalfa, forage; alfalfa, hay; artichoke, globe; barley, grain;
barley, straw; beet, sugar roots; beet, sugar tops; corn, fresh
(including sweet); cotton, undelinted seed; cranberry; cucumber; grape;
grape raisin; grape, raisin, waste; melon; oat, grain; oat, straw;
pepper; rice, straw; sorghum, forage; sorghum, grain grain; sorghum,
grain, stover; strawberry; soybean, forage; soybean, hay; squash;
wheat, grain; and wheat, straw. The second basis is that EPA also
finds, that as outlined in its July 31, 2008 proposed rule, revocation
of these tolerances is warranted on the grounds that aggregate exposure
to residues from these tolerances do not meet the safety standard of
section 408(b)(2) of the FFDCA. The Agency is therefore revoking
tolerances for these crops because aggregate dietary exposure to these
residues of carbofuran, including all anticipated dietary exposures and
all other exposures for which there is reliable information, is not
safe.
    The remaining tolerances the commenters seek to retain are: Banana;
coffee bean; corn, forage; corn, grain; corn, stover; milk; potato;
pumpkin; rice, grain; sugarcane, cane; and sunflower, seed. EPA has
determined that aggregate exposure to carbofuran greater than 0.000075
milligrams/kilogram/day (mg/kg/day) (i.e., greater than the acute
Population Adjusted Dose (aPAD)) does not meet the safety standard of
section 408(b)(2) of the FFDCA. For the 11 remaining tolerances, based
on the contribution from food alone, exposure levels are below EPA's
level of concern. At the 99.9th percentile of exposure, aggregate
carbofuran dietary exposure from food alone was estimated to range
between 0.000020 mg/kg/day for children 6 to 12 years old (29% of the
aPAD) and 0.000058 mg/kg/day (78% of the aPAD) for children 1 to 2
years old, the population subgroup with the highest estimated dietary
exposure. However, EPA's analyses show that those individuals--both
adults and children--who receive their drinking water from sources
vulnerable to carbofuran contamination are exposed to carbofuran levels
that exceed EPA's level of concern--in some cases by orders of
magnitude. This primarily includes those populations consuming drinking
water from ground water from shallow wells in acidic aquifers overlaid
with sandy soils that have had crops treated with carbofuran. Aggregate
exposures from food and from drinking water derived from ground water
in vulnerable areas (e.g., from shallow wells associated with sandy
soils and acidic aquifers) result in significant estimated exceedances.
The estimates for aggregate food and ground water exposure from such
sources range between 780% of the aPAD for adults over 50 years, to
9,400% of the aPAD for infants. Similarly, EPA analyses show
substantial exceedances for those populations that obtain their
drinking water from reservoirs (i.e., surface water) located in small
agricultural watersheds, prone to runoff, and predominated by crops
that are treated with carbofuran, even though there is more uncertainty
associated with these exposure estimates. For example, estimated
aggregate exposures from food and drinking water derived from surface
water, based on corn use in Nebraska, range between 330% of the aPAD
for

youths 13 to 19 years old and 3,900% of the aPAD for infants.
    Every analysis EPA has performed has shown that estimated exposures
from drinking water from each remaining domestic use significantly
exceed EPA's level of concern for children. Accordingly, aggregate
exposures from food and water significantly exceed safe levels.
Although the magnitude of the exceedance varies depending on the level
of conservatism in the assessment, the fact that in each case aggregate
exposures to residues of carbofuran fail to meet the FFDCA section
408(b)(2) safety standard, including where EPA relied on highly refined
estimates of risk, using all relevant data and methods, strongly
corroborates EPA's conclusion that aggregate exposures to residues of
carbofuran are not safe.

B. Overview of Final Rule

    EPA's final rule preamble is organized primarily into two sections.
Following a brief summary of the July 31, 2008 proposed rule, EPA
summarizes the major comments received on the proposed rule, along with
the Agency's responses in Unit VII. Because EPA only presents a summary
of all of the comments received, readers are encouraged to also consult
EPA's Response to Comments Documents, found in the docket for today's
action (Refs. 111, 112, 113). These documents contain EPA's complete
responses to all of the significant comments received on this
rulemaking, and therefore will contain a more detailed explanation on
many of the issues presented in Unit VII.
    Unit VIII. presents the results of EPA's analyses of carbofuran's
dietary risks. This Unit generally describes the bases for the Agency's
conclusions that carbofuran presents unacceptable dietary risks to
children. Readers are also encouraged to consult EPA's underlying risk
assessment support documents, identified in the References section, and
contained in the docket for today's action, for a more detailed
presentation of EPA's scientific analyses.
    Each of these units is generally organized consistent with the
structure of a risk assessment. Each unit begins with a discussion of
carbofuran's toxicity, and EPA's hazard identification, including a
discussion of the issues surrounding the selection of the children's
safety factor EPA has applied to this chemical. EPA then discusses
issues relating to carbofuran's exposures from food and drinking water.
The final section of each unit relates to EPA's conclusions regarding
the risks from carbofuran's aggregate (i.e., food + water) exposures.

C. What Is the Agency's Authority for Taking This Action?

    EPA is taking this action, pursuant to the authority in FFDCA
sections 408(b)(1)(b), 408(b)(2)(A), and 408(e)(1)(A). 21 U.S.C.
346a(b)(1)(b), (b)(2)(A), (e)(1)(A).

III. Statutory and Regulatory Background

    A ``tolerance'' represents the maximum level for residues of
pesticide chemicals legally allowed in or on raw agricultural
commodities (including animal feed) and processed foods. Section 408 of
FFDCA, 21 U.S.C. 346a, as amended by the Food Quality Protection Act
(FQPA) of 1996, Public Law 104-170, authorizes the establishment of
tolerances, exemptions from tolerance requirements, modifications to
tolerances, and revocation of tolerances for residues of pesticide
chemicals in or on raw agricultural commodities and processed foods.
Without a tolerance or exemption, food containing pesticide residues is
considered to be unsafe and therefore ``adulterated'' under section
402(a) of the FFDCA, 21 U.S.C. 342(a). Such food may not be distributed
in interstate commerce (21 U.S.C. 331(a)). For a food-use pesticide to
be sold and distributed, the pesticide must not only have appropriate
tolerances under the FFDCA, but also must be registered under the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C.
136 et seq.). Food-use pesticides not registered in the United States
must have tolerances in order for commodities treated with those
pesticides to be imported into the United States.
    Section 408(e) of the FFDCA, 21 U.S.C. 346a(e), authorizes EPA to
modify or revoke tolerances on its own initiative. EPA is revoking
these tolerances to implement the Agency's findings made during the
reregistration and tolerance reassessment processes. As part of these
processes, EPA is required to determine whether each of the existing
tolerances meets the safety standard of section 408(b)(2) (21 U.S.C.
346a(b)(2)). Section 408(b)(2)(A)(i) of the FFDCA requires EPA to
modify or revoke a tolerance if EPA determines that the tolerance is
not ``safe'' (21 U.S.C. 346a(b)(2)(A)(i)). Section 408(b)(2)(A)(ii) of
the FFDCA defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information'' (21
U.S.C. 346a(b)(2)(A)(ii). This includes exposure through drinking water
and in residential settings, but does not include occupational
exposure.
    Risks to infants and children are given special consideration.
Specifically, section 408(b)(2)(C) states that EPA:

    shall assess the risk of the pesticide chemical based on-- . . .
    (II) available information concerning the special susceptibility
of infants and children to the pesticide chemical residues,
including neurological differences between infants and children and
adults, and effects of in utero exposure to pesticide chemicals; and
    (III) available information concerning the cumulative effects on
infants and children of such residues and other substances that have
a common mechanism of toxicity. . . .

    (21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)).
    This provision further directs that ``[i]n the case of threshold
effects, . . .an additional tenfold margin of safety for the pesticide
chemical residue and other sources of exposure shall be applied for
infants and children to take into account potential pre- and post-natal
toxicity and completeness of the data with respect to exposure and
toxicity to infants and children'' (21 U.S.C. 346a(b)(2)(C)). EPA is
permitted to ``use a different margin of safety for the pesticide
chemical residue only if, on the basis of reliable data, such margin
will be safe for infants and children'' (Id.). The additional safety
margin for infants and children is referred to throughout this final
rule as the ``children's safety factor.''

IV. Carbofuran Background and Regulatory History

    In July 2006, EPA completed a refined acute probabilistic dietary
risk assessment for carbofuran as part of the reassessment program
under section 408(q) of the FFDCA. The assessment was conducted using
Dietary Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCID\TM\, Version 2.03), which incorporates consumption data from the
United States Department of Agriculture's (USDA's) Nationwide
Continuing Surveys of Food Intake by Individuals (CSFII), 1994-1996 and
1998, as well as carbofuran monitoring data from USDA's Pesticide Data
Program\1\ (PDP), estimated percent crop treated information, and
processing/cooking factors, where applicable. The assessment was
conducted applying a

500-fold safety factor that included a 5X children's safety factor,
pursuant to section 408(b)(2)(C). That refined assessment showed acute
dietary risks from carbofuran residues in food above EPA's level of
concern (Ref. 19). Since 2006, EPA has evaluated additional data
submitted by the registrant, FMC Corporation, and has further refined
its original assessment by incorporating more recent 2005/2006 PDP
data, and by conducting additional analyses. In January 2008, EPA
published a draft Notice of Intent to Cancel (NOIC) all carbofuran
registrations, based in part on carbofuran's dietary risks. As mandated
by FIFRA, EPA solicited comments from the FIFRA Scientific Advisory
Panel (SAP) on its draft NOIC. Having considered the comments from the
SAP, EPA initiated the process to revoke all carbofuran tolerances,
publishing its proposed revocation on July 31, 2008 (73 FR 44864). The
comment period for the proposed rule closed on September 29, 2008.
Having considered all comments received by this date, EPA is now
finalizing the revocation of all existing carbofuran tolerances. As
noted above, aggregate exposures from food and water to the U.S.
population at the upper percentiles of exposure substantially exceed
the safe daily levels and thus are ``unsafe'' within the meaning of
FFDCA section 408(b)(2) (Ref. 71). It is particularly significant that
under every analysis EPA has conducted, the levels of carbofuran exceed
the safe daily dose for children, even when EPA used the most refined
data and models available. Based on these findings, EPA has decided to
move expeditiously to address the unacceptable dietary risks to
children. EPA anticipates issuing the NOIC subsequent to undertaking
the activities required to revoke the carbofuran tolerances.
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    \1\ USDA's Pesticide Data Program monitors for pesticides in
certain foods at the distribution points just before release to
supermarkets and grocery stores.
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V. EPA's Approach to Dietary Risk Assessment

    EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. A short summary is provided
below to aid the reader. For further discussion of the regulatory
requirements of section 408 of the FFDCA and a complete description of
the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/
1999/January/Day-04/p34736.htm
    To assess the risk of a pesticide tolerance, EPA combines
information on pesticide toxicity with information regarding the route,
magnitude, and duration of exposure to the pesticide. The risk
assessment process involves four distinct steps: (1) Identification of
the toxicological hazards posed by a pesticide; (2) determination of
the exposure ``level of concern'' for humans; (3) estimation of human
exposure; and (4) characterization of human risk based on comparison of
human exposure to the level of concern.

A. Hazard Identification and Selection of Toxicological Endpoint

    Any risk assessment begins with an evaluation of a chemical's
inherent properties, and whether those properties have the potential to
cause adverse effects (i.e., a hazard identification). EPA then
evaluates the hazards to determine the most sensitive and appropriate
adverse effect of concern, based on factors such as the effect's
relevance to humans and the likely routes of exposure.
    Once a pesticide's potential hazards are identified, EPA determines
a toxicological level of concern for evaluating the risk posed by human
exposure to the pesticide. In this step of the risk assessment process,
EPA essentially evaluates the levels of exposure to the pesticide at
which effects might occur. An important aspect of this determination is
assessing the relationship between exposure (dose) and response (often
referred to as the dose-response analysis). In evaluating a chemical's
dietary risks EPA uses a reference dose (RfD) approach, which involves
a number of considerations including:
     A ``point of departure'' (PoD)--the value from a dose-
response curve that is at the low end of the observable data and that
is the toxic dose that serves as the `starting point' in extrapolating
a risk to the human population.
     An uncertainty factor to address the potential for a
difference in toxic response between humans and animals used in
toxicity tests (i.e., interspecies extrapolation).
     An uncertainty factor to address the potential for
differences in sensitivity in the toxic response across the human
population (for intraspecies extrapolation).
     The need for an additional safety factor to protect
infants and children, as specified in FFDCA section 408(b)(2)(C).
    EPA uses the chosen PoD to calculate a safe dose or RfD. The RfD is
calculated by dividing the chosen PoD by all applicable safety or
uncertainty factors. Typically in EPA risk assessments, a combination
of safety or uncertainty factors providing at least a hundredfold
(100X) margin of safety is used: 10X to account for interspecies
extrapolation and 10X to account for intraspecies extrapolation.
Further, in evaluating the dietary risks for pesticide chemicals, an
additional safety factor of 10X is presumptively applied to protect
infants and children, unless reliable data support selection of a
different factor. In implementing FFDCA section 408, EPA also
calculates a variant of the RfD referred to as a Population Adjusted
Dose (PAD). A PAD is the RfD divided by any portion of the children's
safety factor that does not correspond to one of the traditional
additional uncertainty/safety factors used in general Agency risk
assessment. The reason for calculating PADs is so that other parts of
the Agency, which are not governed by FFDCA section 408, can, when
evaluating the same or similar substances, easily identify which
aspects of a pesticide risk assessment are a function of the particular
statutory commands in FFDCA section 408. For acute assessments, the
risk is expressed as a percentage of a maximum acceptable dose or the
acute PAD (i.e., the acute dose which EPA has concluded will be
``safe''). As discussed below in Unit V.C., dietary exposures greater
than 100% of the acute PAD are generally cause for concern and would be
considered ``unsafe'' within the meaning of FFDCA section 408(b)(2)(B).
Throughout this document general references to EPA's calculated safe
dose are denoted as an acute PAD, or aPAD, because the relevant point
of departure for carbofuran is based on an acute risk endpoint.
    Carbofuran is a member of the class of pesticides called n-methyl
carbamates (NMCs). The primary toxic effect caused by NMCs, including
carbofuran, is neurotoxicity resulting from inhibition of the enzyme
acetylcholinesterase (AChE, See Unit VIII.A.). The toxicity profile of
these pesticides is characterized by rapid time to onset of effects
followed by rapid recovery (minutes to hours). Consistent with its
mechanism of action, toxicity data on AChE inhibition from laboratory
rats provide the basis for deriving the PoD for carbofuran.

B. Estimating Human Dietary Exposure Levels

    Pursuant to section 408(b) of the FFDCA, EPA has evaluated
carbofuran's dietary risks based on ``aggregate exposure'' to
carbofuran. By ``aggregate exposure,'' EPA is referring to exposure to
carbofuran by multiple pathways of exposure. EPA uses available data
and standard analytical methods, together with assumptions designed to
be protective of public health, to produce separate estimates of
exposure for a highly exposed subgroup of the general population, for
each potential pathway and route of exposure. For acute risks,

EPA then calculates potential aggregate exposure and risk by using
probabilistic \2\ techniques to combine distributions of potential
exposures in the population for each route or pathway. For dietary
analyses, the relevant sources of potential exposure to carbofuran are
from the ingestion of residues in food and drinking water. The Agency
uses a combination of monitoring data and predictive models to evaluate
environmental exposure of humans to carbofuran.
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    \2\ Probabilistic analysis is used to predict the frequency with
which variations of a given event will occur. By taking into account
the actual distribution of possible consumption and pesticide
residue values, probabilistic analysis for pesticide exposure
assessments ``provides more accurate information on the range and
probability of possible exposure and their associated risk values''
(Ref. 101). In capsule, a probabilistic pesticide exposure analysis
constructs a distribution of potential exposures based on data on
consumption patterns and residue levels and provides a ranking of
the probability that each potential exposure will occur. People
consume differing amounts of the same foods, including none at all,
and a food will contain differing amounts of a pesticide residue,
including none at all.
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    1. Exposure from Food. Data on the residues of carbofuran in foods
are available from a variety of sources. One of the primary sources of
data comes from federally conducted surveys, including the PDP
conducted by the USDA. Further, market basket surveys, which are
typically performed by registrants, can provide additional residue
data. These data generally provide a characterization of pesticide
residues in or on foods consumed by the U.S. population that closely
approximates real world exposures because they are sampled closer to
the point of consumption in the chain of commerce than field trial
data, which are generated to establish the maximum level of legal
residues that could result from maximum permissible use of the
pesticide. In certain circumstances, when EPA believes the information
will provide more accurate exposure estimates, EPA will rely on field
trial data (see below in Unit VIII.E.1.).
    EPA uses a computer program known as the DEEM-FCID\TM\ to estimate
exposure by combining data on human consumption amounts with residue
values in food commodities. DEEM-FCID\TM\ also compares exposure
estimates to appropriate RfD or PAD values to estimate risk. EPA uses
DEEM-FCID\TM\ to estimate exposure for the general U.S. population as
well as for 32 subgroups based on age, sex, ethnicity, and region.
DEEM-FCID\TM\ allows EPA to process extensive volumes of data on human
consumption amounts and residue levels in making risk estimates.
Matching consumption and residue data, as well as managing the
thousands of repeated analyses of the consumption database conducted
under probabilistic risk assessment techniques, requires the use of a
computer.
    DEEM-FCID\TM\ contains consumption and demographic information on
the individuals who participated in the USDA's CSFII in 1994-1996 and
1998. The 1998 survey was a special survey required by the FQPA to
supplement the number of children survey participants. DEEM-FCID\TM\
also contains ``recipes'' that convert foods as consumed (e.g., pizza)
back into their component raw agricultural commodities (e.g., wheat
from flour, or tomatoes from sauce). This is necessary because residue
data are generally gathered on raw agricultural commodities rather than
on finished ready-to-eat food. Data on residue values for a particular
pesticide and the RfD or PADs for that pesticide are inputs to the
DEEM-FCID\TM\ program to estimate exposure and risk.
    For carbofuran's assessment, EPA used DEEM-FCID\TM\ to calculate
risk estimates based on a probabilistic distribution. DEEM-FCID\TM\
combines the full range of residue values for each food with the full
range of data on individual consumption amounts to create a
distribution of exposure and risk levels. More specifically, DEEM-
FCID\TM\ creates this distribution by calculating an exposure value for
each reported day of consumption per person (``person-day'') in CSFII,
assuming that all foods potentially bearing the pesticide residue
contain such residue at a value selected randomly from the
concentration data sets. The exposure amounts for the thousands of
person-days in the CSFII are then collected in a frequency
distribution. EPA also uses DEEM-FCID\TM\ to compute a distribution
taking into account both the full range of data on consumption levels
and the full range of data on potential residue levels in food.
Combining consumption and residue levels into a distribution of
potential exposures and risk requires use of probabilistic techniques.
    The probabilistic technique that DEEM-FCID\TM\ uses to combine
differing levels of consumption and residues involves the following
steps:
    (1) Identification of any food(s) that could bear the residue in
question for each person-day in the CSFII.
    (2) Calculation of an exposure level for each of the thousands of
person-days in the CSFII database, based on the foods identified in
Step 1 by randomly selecting residue values for the foods from
the residue database.
    (3) Repetition of Step 2 one thousand times for each
person-day.
    (4) Collection of all of the hundreds of thousands of potential
exposures estimated in Steps  2 and 3 in a frequency
distribution.
    The resulting probabilistic assessment presents a range of
exposure/risk estimates.
    2. Exposure from water. EPA may use field monitoring data and/or
simulation water exposure models to generate pesticide concentration
estimates in drinking water. Monitoring and modeling are both important
tools for estimating pesticide concentrations in water and can provide
different types of information. Monitoring data can provide estimates
of pesticide concentrations in water that are representative of the
specific agricultural or residential pesticide practices in specific
locations, under the environmental conditions associated with a
sampling design (i.e., the locations of sampling, the times of the year
samples were taken, and the frequency by which samples were collected).
Although monitoring data can provide a direct measure of the
concentration of a pesticide in water, it does not always provide a
reliable basis for estimating spatial and temporal variability in
exposures because sampling may not occur in areas with the highest
pesticide use, and/or when the pesticides are being used and/or at an
appropriate sampling frequency to detect high concentrations of a
pesticide that occur over the period of a day to several days.
    Because of the limitations in most monitoring studies, EPA's
standard approach is to use simulation water exposure models as the
primary means to estimate pesticide exposure levels in drinking water.
Modeling is a useful tool for characterizing vulnerable sites, and can
be used to estimate peak pesticide water concentrations from
infrequent, large rain events. EPA's computer models use detailed
information on soil properties, crop characteristics, and weather
patterns to estimate water concentrations in vulnerable locations where
the pesticide could be used according to its label (69 FR 30042, 30058-
30065, May 26, 2004) (FRL-7355-7). These models calculate estimated
water concentrations of pesticides using laboratory data that describe
how fast the pesticide breaks down to other chemicals and how it moves
in the environment at these vulnerable locations. The modeling provides
an estimate of pesticide concentrations in ground water and surface
water. Depending on the modeling algorithm (e.g., surface water
modeling scenarios), daily concentrations can be estimated

continuously over long periods of time, and for places that are of most
interest for any particular pesticide.
    EPA relies on models it has developed for estimating pesticide
concentrations in both surface water and ground water. Typically EPA
uses a two-tiered approach to modeling pesticide concentrations in
surface and ground water. If the first tier model suggests that
pesticide levels in water may be unacceptably high, a more refined
model is used as a second tier assessment. The second tier model for
surface water is actually a combination of two models: The Pesticide
Root Zone Model (PRZM) and the Exposure Analysis Model System (EXAMS).
The second tier model for ground water uses PRZM alone.
    A detailed description of the models routinely used for exposure
assessment is available from the EPA OPP Water Models web site: http://
www.epa.gov/oppefed1/models/water/index.htm. These models provide a
means for EPA to estimate daily pesticide concentrations in surface
water sources of drinking water (a reservoir) using local soil, site,
hydrology, and weather characteristics along with pesticide application
and agricultural management practices, and pesticide environmental fate
and transport properties. Consistent with the recommendations of the
FIFRA SAP, EPA also considers regional percent cropped area factors
(PCA) which take into account the potential extent of cropped areas
that could be treated with pesticides in a particular area. The PRZM
and EXAMS models used by EPA were developed by EPA's Office of Research
and Development (ORD), and are used by many international pesticide
regulatory agencies to estimate pesticide exposure in surface water.
EPA's use of the PCA area factors and the Index Reservoir scenario was
reviewed by the FIFRA SAP in 1999 and 1998, respectively (Refs. 37 and
38).
    In modeling potential surface water concentrations, EPA attempts to
model areas of the country that are vulnerable to surface water
contamination rather than simply model ``typical'' concentrations
occurring across the nation. Consequently, EPA models exposures
occurring in small highly agricultural watersheds in different growing
areas throughout the country, over a 30-year period. The scenarios are
designed to capture residue levels in drinking water from reservoirs
with small watersheds with a large percentage of land use in
agricultural production. EPA believes these assessments are likely
reflective of a small subset of the watersheds across the country that
maintain drinking water reservoirs, representing a drinking water
source generally considered to be more vulnerable to frequent high
concentrations of pesticides than most locations that could be used for
crop production.
    EPA uses the output of daily concentration values from tier two
modeling as an input to DEEM-FCID\TM\, which combines water
concentrations with drinking water consumption information in the daily
diet to generate a distribution of exposures from consumption of
drinking water contaminated with pesticides. These results are then
used to calculate a probabilistic assessment of the aggregate human
exposure and risk from residues in food and drinking water.
    3. Aggregate exposure analyses. Using probabilistic analyses, EPA
combines the national food exposures with the exposures derived for
individual region and crop-specific drinking water scenarios to derive
estimates of aggregate exposure. Although food is distributed
nationally, and residue values are therefore not expected to vary
substantially throughout the country, drinking water is locally derived
and concentrations of pesticides in source water fluctuate over time
and location for a variety of reasons. Pesticide residues in water
fluctuate daily, seasonally, and yearly as a result of the timing of
the pesticide application, the vulnerability of the water supply to
pesticide loading through runoff, spray drift and/or leaching, and
changes in the weather. Concentrations are also affected by the method
of application, the location and characteristics of the sites where a
pesticide is used, the climate, and the type and degree of pest
pressure.
    EPA's standard acute dietary exposure assessment calculates total
dietary exposure over a 24-hour period; that is consumption over 24
hours is summed and no account is taken of the fact that eating and
drinking occasions may spread out exposures over a day. This total
daily exposure generally provides reasonable estimates of the risks
from acute dietary exposures, given the nature of most chemical
endpoints. Due to the rapid recovery associated with carbofuran
toxicity (AChE inhibition), 24-hour exposure periods may or may not, a
priori, be appropriate. To the extent that a day's eating or drinking
occasions leading to high total daily exposure might be found close
together in time, or to occur from a single eating event, minimal AChE
recovery would occur between eating occasions (i.e., exposure events).
In that case, the ``24-hour sum'' approach, which sums eating events
over a 24-hour period, would provide reasonable estimates of risk from
food and drinking water. Conversely, to the extent that eating
occasions leading to high total daily exposures are widely separated in
time (within 1 day) such that substantial AChE recovery occurs between
eating occasions, then the estimated risks under any 24-hour sum
approach may be overstated. In that case, a more sophisticated approach
- one that accounts for intra-day eating and drinking patterns and the
recovery of AChE between exposure events -- may be more appropriate.
This approach is referred to as the ``Eating Occasions Analysis'' and
it takes into account the fact that the toxicological effect of a first
dose may be reduced or tempered prior to a second (or subsequent) dose.
    Thus, rather than treating a full day's exposure as a one-time
``bolus'' dose, as is typically done in the Agency's assessments, the
Eating Occasion Analysis uses the actual time of eating or drinking
occasion, and amounts consumed as reported by individuals to the USDA
CSFII. The actual CSFII-recorded time of each eating event is used to
``separate out'' the exposures due to each eating occasion; in doing
so, this ``separation'' allows the Agency to distinguish between each
intake event and account for the fact that at least some partial
recovery of AChE inhibition attributable to the first (earlier)
exposure occurs before the second exposure event. For chemicals for
which the toxic effect is rapidly reversible, the time between two (or
more) exposure events permits partial to full recovery from the toxic
effect from the first exposure and it is this ``partial recovery'' that
is specifically accounted for by the Eating Occasion Analysis. More
specifically, an estimated ``persisting dose'' from the first exposure
event is added to the second exposure event to account for the partial
recovery of AChE inhibition that occurs over the time between the first
and second exposures. The ``persisting dose'' terminology, and this
general approach were originally offered by the FIFRA SAP in the
context of assessing AChE inhibition from cumulative exposures to
organophosphorous pesticides (OPs) (Ref. 40).

C. Selection of Acute Dietary Exposure Level of Concern

    Because probabilistic assessments generally present a realistic
range of residue values to which the population may be exposed, EPA's
starting point for estimating exposure and risk for such aggregate
assessments is the 99.9th percentile of the population under

evaluation, which represents one person out of every 1,000 persons.
When using a probabilistic method of estimating acute dietary exposure,
EPA typically assumes that, when the 99.9th percentile of acute
exposure is equal to or less than the aPAD, the level of concern for
acute risk has not been exceeded. By contrast, where the analysis
indicates that estimated exposure at the 99.9th percentile exceeds the
aPAD, EPA would generally conduct one or more sensitivity analyses to
determine the extent to which the estimated exposures at the high-end
percentiles may be affected by unusually high food consumption or
residue values. To the extent that one or a few values seem to
``drive'' the exposure estimates at the high end of exposure, EPA would
consider whether these values are reasonable and should be used as the
primary basis for regulatory decision making (Ref. 101).

VI. Summary of the Proposed Rule

    EPA proposed to revoke all of the existing tolerances for residues
of carbofuran on the grounds that aggregate exposure from all uses of
carbofuran fail to meet the FFDCA section 408 safety standard (73 FR
44864). Based on the contribution from food alone, EPA calculated that
dietary exposures to carbofuran exceeded EPA's level of concern for all
of the more sensitive subpopulations of infants and children. At the
99.9th percentile, carbofuran dietary exposure from food alone was
estimated at 0.000082 mg/kg/day (110% of the aPAD) for children 3-5
years old, the population subgroup with the highest estimated dietary
exposure (Ref. 16). In addition, EPA's analyses showed that those
individuals--both adults as well as children--who receive their
drinking water from vulnerable sources are also exposed to levels that
exceed EPA's level of concern--in some cases by orders of magnitude.
This primarily included those populations consuming drinking water from
ground water from shallow wells in acidic aquifers overlaid with sandy
soils that have had crops treated with carbofuran. It also included
those populations that obtain their drinking water from reservoirs
located in small agricultural watersheds, prone to runoff, and
predominated by crops that are treated with carbofuran, although there
was more uncertainty associated with these exposure estimates. The
proposal discussed a number of sensitivity analyses the Agency had
conducted in order to further characterize the potential risks to
children. Every one of these sensitivity analyses determined that
estimated exposures significantly exceeded EPA's level of concern for
children.

VII. Summary of Public Comments and EPA Responses

    This section presents a summary of some of the significant comments
received on the proposed rule, as well as the Agency's responses. More
detailed responses to these comments, along with the Agency's responses
to other comments received can be found in the Response to Comments
Documents, located in the docket for this rulemaking (Refs. 111, 112,
and 113).

A. Tolerances Associated With Voluntarily Canceled Uses

    On September 29, 2008, the registrant, FMC Corporation requested
EPA to eliminate several uses from their end-use products. Consistent
with this request, the registrant has indicated that it no longer seeks
to maintain the tolerances associated with the domestic use of these
products, and therefore no longer opposes the revocation of those
tolerances. No other commenter indicated any interest in maintaining
these tolerances. EPA is therefore revoking the tolerances associated
with those domestic uses, on two separate grounds. The first ground is
that the tolerances will no longer be necessary because the
registrations for these uses have been canceled. The tolerances that
EPA is revoking on this basis are: Alfalfa, forage; alfalfa, hay;
artichoke, globe; barley, grain; barley, straw; beet, sugar roots;
beet, sugar tops; corn, fresh (including sweet); corn, popcorn; cotton,
undelinted seed; cranberry; cucumber; grape; grape raisin; grape,
raisin, waste; melon; oat, grain; oat, straw; pepper; rice, straw;
sorghum, forage; sorghum, grain grain; sorghum, grain, stover;
strawberry; soybean, forage; soybean, hay; squash; wheat, grain; and
wheat, straw.
    EPA also finds, however, that revocation of these tolerances is
warranted on the grounds that aggregate exposures to these residues of
carbofuran do not meet the safety standard of section 408(b)(2) of the
FFDCA. The Agency is therefore revoking tolerances for these crops
because aggregate dietary exposures to residues of carbofuran,
including all anticipated dietary exposures and all other exposures for
which there is reliable information, are not safe.
    As noted in the proposed rule, based on the contribution from only
the foods bearing residues resulting from all of these tolerances,
dietary exposures to carbofuran would be unsafe for the more sensitive
children's subpopulations. At the 99.9th percentile, carbofuran dietary
exposure from food alone was estimated at 0.000082 mg/kg/day (110% of
the aPAD) for children 3-5 years old, the population subgroup with the
highest estimated dietary exposure (Ref. 70). In addition, as discussed
in more detail, both in the proposed rule, and in Unit VIII.E.2. below,
drinking water residues of carbofuran contribute significantly to
unsafe aggregate exposures. Accordingly, it has not been shown that
exposures from these uses would meet the FFDCA safety standard.

B. Comments Relating to EPA's Toxicology Assessment

    1. Comments relating to EPA's PoD. One group of commenters stated
that the studies clearly support EPA's conclusion that the post-natal
day (PND)11 brain data on the inhibition of AChE in juvenile rats
provide the most appropriate PoD for risk assessment. The commenters
also claimed, however, that ``the specific PoD proposed by EPA is 0.03
mg/kg/day, but our analysis of the best data for the risk assessment
are found in the good laboratory practices (GLP) compliant studies and
those studies support 0.033 as a better value for the PND11 rat.'' This
group of commenters also described an analysis their consultant had
conducted. According to the commenters, their consultant calculated the
value of 0.033 mg/kg/day/day from the BMD10s and
BMDL10s \3\ in the four FMC studies with first observation
time equal to 0.25 hours. The BMDs and BMDLs were calculated separately
for each of these datasets. The results for the four datasets were
combined, but, unlike EPA's analyses, the datasets themselves were not
combined.
---------------------------------------------------------------------------

    \3\ BMD is an abbreviation for benchmark dose. The
BMDL10 is the lower 95% confidence limit on the
BMD10. The BMD10 is the estimated dose (i.e.,
benchmark dose) to result in 10% AChE inhibition. EPA uses the BMDL,
not the BMD, as the point of departure.
---------------------------------------------------------------------------

    With respect to using the PND11 rat pup data as the PoD, the Agency
acknowledges this area of agreement with the commenters. Ultimately,
the BMDL10 recommended by the commenters differs from the
EPA's BMDL10 by only 6% (0.031 mg/kg/day vs. 0.033 mg/kg/
day), a difference that is not biologically significant. Moreover, when
rounded to one significant digit, as is done by typical convention and
consistent with the dose information provided in the comparative
cholinesterase (ChE) studies (also called CCA studies), both values
yield the identical PoD of 0.03 mg/kg/day.
    Moreover, the Agency notes that the value of 0.033 mg/kg/day
recommended

by the commenter does not include the 0.5-hr time-point from MRID no.
47143705 although this dataset yielded the lowest BMDL for individual
datasets reported by the commenters. As such, the commenter's
recommended value does not include all of the relevant data collected
at the time of peak effect. The commenters have provided no rationale
for why it would be appropriate to selectively exclude data from the
time frame in this study most relevant to the risk assessment.
Accordingly, as noted in footnote 115 of the comment, when the
commenters included the data at 0.5-hr timepoint from MRID no.
47143705, the BMDL10 was lowered from 0.033 to 0.030 mg/kg/
day--a value almost identical to the Agency's BMDL10 of
0.031 mg/kg/day.
    Thus, although the commenters are critical of the Agency's
approach, there is basic consensus between EPA and the commenters that
the PoD is 0.03 mg/kg/day given the precision of available data in
deriving the BMDL10.
    The Agency also notes that specific details about the commenter's
BMD modeling were not provided to the Agency. The Agency is therefore
unable to fully evaluate the scientific validity of the modeling
procedure used by the commenter.
    Some commenters claimed that ``EPA's derivation of its PoD,
however, is not transparent and is not scientifically supported.
Equally important, based on a recent review of the raw data from the
Moser study (obtained via a FOIA request originally filed in April
2008), we believe that the Moser study may not meet minimum criteria
for scientific acceptability. Critical data are simply unavailable for
this study, including: a complete protocol, analysis of dosing
solutions, clinical observations, standardization of brain and red
blood cell (RBC) AChE results in terms of amount per unit of protein,
and quality assurance records of inspections for the carbofuran portion
of the study.'' As a result, the commenters assert that the better
approach is to use the brain AChE inhibition values calculated from the
GLP-compliant registrant studies, because the commenters claim that EPA
has acknowledged them to be valid, and which the commenters claim are
fully documented. Using EPA's BMD dose-time response model, the
commenters claim that the correct PoD is 0.033 mg/kg/day.
    The Agency disagrees with the commenters' assertions that the
derivation of the PoD was not transparent. The Agency's analysis,
computer code, and data have been placed in the docket for public
scrutiny. EPA's models have been repeatedly reviewed and approved by
the FIFRA SAP (Refs. 42, 43, and 44), and, as part of that process,
been made available to the public. The most recent occasion was as part
of the February 2008 FIFRA SAP meeting on the draft carbofuran NOIC. As
EPA has explained numerous times, the Agency has not deviated from its
standard practice. Most recently, EPA laid out its approach at length
in the proposed rule. While it is true that EPA may not have repeated
in this most recent analysis all of the specifics that it has
previously provided, it is inaccurate for the commenter to claim that
the information is not available, or that its review has in any way
been hampered by this so-called lack of transparency. Indeed, given
that the commenters appear to have been able to duplicate EPA's
analyses, it seems reasonable to assume that the information was
available. It is further worth noting that the commenters had
sufficient access to the Moser data to allow a complete re-analysis
before the 2008 SAP on the draft carbofuran NOIC, which was months
before the FOIA request was filed with the Agency. In addition, a
complete study protocol as well as a report of the quality assurance
(QA) technical and data reviews of the study were included in the
documents provided in response to the FOIA request. The Agency further
notes that although the commenters complain about their perceived lack
of transparency in EPA's BMD calculations, they did not provide any
detailed information about the derivation of their proposed value.
    EPA also disagrees with the claim that EPA's PoD is not
scientifically supported. As an initial matter, EPA notes that the
commenters' suggested PoD of 0.033 mg/kg/day is not significantly
different than EPA's PoD of 0.03 mg/kg/day (see Unit VIII.B.). The
criticisms of the Moser study are also incorrect. The procedures and
documentation are in accordance with the ORD Quality Assurance
Management Plan. Concerning standardization of brain and RBC AChE in
terms of protein, it is interesting to note that, despite their
complaints that EPA had failed to do this, the registrant also failed
to do this in their own studies. However, in the Moser study, the AChE
activity was standardized in terms of tissue weight per ml, so the
amount of protein was consistent across samples. This is an acceptable
and widely used practice. Further, abnormal (or ``clinical'')
observations were recorded when they occurred; however, it is not
technically possible to observe the animals while they are being tested
for motor activity. Finally, the registrant is correct that the dosing
solutions for the CCA study were not analyzed, but this was done for
the adult studies in McDaniel et al., (2007), and the preparation and
stability of the carbofuran samples were confirmed therein.
    If, however, the Agency elected to follow the commenters'
recommendation to not use the ORD data in the risk assessment, there
would be no high quality RBC AChE inhibition data available in juvenile
rats. As such, there would be no surrogate data evaluating AChE
inhibition in the peripheral nervous system (PNS), much less any data
from the PNS itself. As discussed in Unit VIII.C., with the
availability of some RBC data from ORD evaluating the effects in the
PNS, the Agency is able to reduce the children's safety factor from 10X
to 4X. Without the ORD data, the Agency would be required to retain the
statutory 10X.
    Some commenters raised concern that EPA's PoD was not sufficiently
protective. The commenters point to comments from the February SAP
review of EPA's draft carbofuran NOIC, quoting the following language
from the report, which indicated concern that the starting point used
in the risk assessment was not sufficiently protective:

    Some Panel members questioned the assumption that a 10% level of
brain AChE inhibition (i.e., BMD10) is sufficiently
harmless to be used as a point of departure in risk assessment. It
was noted that as more refined brain data become available, we are
beginning to understand that not all regions of this organ show the
same level of AChE inhibition. Thus a 10% inhibition for the whole
brain may imply significantly greater inhibition in a more sensitive
region.

    The FIFRA SAP report provides conflicting information on the issue
of the benchmark dose response used by EPA in its BMD calculations. On
page 53 of the FIFRA SAP report, the text suggests that the available
data do not support the 10% response level used in BMD modeling and
that a 20% response level is more appropriate. The text quoted by the
commenters from the report argues that a 10% response level may not be
sufficiently health protective, but that a 5% response level may be
more appropriate. Given the lack of unanimous advice by the Panel in
this case, and that past SAPs have previously supported the use of a
10% level in comparable cases, the Agency has concluded that the
overall weight of the available evidence supports a decision that use
of a 10% response level will be protective of human health.

A more detailed response to this issue can be found in the Agency's
response to the SAP (Ref. 109).
    2. Comments relating to the children's safety factor--a. Reliance
on RBC to predict effects on the PNS. Some commenters argued that brain
is a better surrogate for the PNS than RBC, and that therefore reliance
on the brain data is sufficiently protective that no additional
children's safety factor is necessary. The commenters claim that the
carbofuran data on brain AChE inhibition and on clinical signs of
toxicity indicate that PNS AChE inhibiton is sufficiently modeled by
brain AChE inhibtion. They note that the available data show that brain
AChE responds rapidly to carbofuran; it readily passes the blood-brain
barrier and the data show maximal AChE inhibition within minutes. The
commenters also alleged that brain and tissue AChE are more similar to
each other than to RBC AChE. The commenters also point to the fact that
oral time-course studies by EPA and the registrant show that brain
cholinesterase responds quickly and recovers promptly. Carbofuran
clearly reaches the brain quickly. They also cite to the fact that EPA
has acknowledged that in adults, no difference in sensitivity is seen
between brain and RBC AChE inhibition.
    The commenters repeatedly mention the rapid speed by which
carbofuran reaches the brain and the rapid onset and recovery of AChE
inhibition as support for the notion that reliance on the brain data
will be adequately protective of PNS toxicity. The Agency agrees with
the commenters on the rapid nature of carbofuran toxicity. However,
this rapid toxicity occurs in multiple tissues, not just the brain.
Moreover, the time course of such toxicity is not relevant to
determining which tissue is more sensitive. Therefore, these comments
are not relevant to a discussion of the use of brain versus RBC AChE as
a surrogate for PNS toxicity.
    The commenters' allegation that brain and tissue AChE are more
similar to each other than to RBC AChE is not scientifically
supportable. Radic and Taylor (2006), for example, state, ``In humans
and most other vertebrate species, only one gene encodes AChE'' (Ref.
81). Accordingly, if only one gene encodes the enzyme, then the
structure of the active site is the same throughout the body.
    Responses in adult animals are not necessarily predictive or
relevant to responses in juveniles since the metabolic capacity of
juveniles is less than that of adults. As such, juveniles can be more
sensitive to some toxic agents. Specific to carbofuran, multiple
studies have shown juvenile rats to be more sensitive than adult rats.
Thus, comments about responses in adults are less relevant compared to
data in pups from the carbofuran risk assessment, particularly in the
evaluation of the children's safety factor.
    One group of commenters argue that there is evidence that RBC AChE
activity can be inhibited to a greater degree than AChE in peripheral
organs. For example, Marable et al., (2007), showed that chlorpyrifos
caused much greater inhibition of AChE in RBC than in diaphragm, left
atrium, and quadriceps, as well as in brain. Similarly, Padilla et al.,
(2005), reported a greater inhibition of AChE in RBC than in diaphragm
or brain. Bretaud et al., (2000), showed that carbofuran caused
significant inhibition of AChE in brain tissues but not in muscle in
goldfish. The commenters claim that these results demonstrate that RBC
AChE activity does not reflect AChE activity in peripheral organs.
    The commenters mention three references: Padilla et al., 2005;
Marable et al., 2007; Bretaud et al., 2000. Two of these studies
involve testing with chlorpyrifos in rats (Refs. 65 and 77) and the
third involves testing fish with carbofuran (Ref. 14). Quantitative
extrapolation of RBC and peripheral AChE inhibition differences from
fish to mammals is highly uncertain because distribution of carbofuran
across fish and mammalian tissues may be quite different. The Padilla
et al., (2005) and Marable et al., (2007) references include testing
with chlorpyrifos, an OP whose primary mode of action is also AChE
inhibition (Refs. 65 and 77). Exposure to OP and NMC insecticides
results in inhibition of AChE. The Agency assumes it is this similarity
in mechanism of toxicity, which provides the basis for inclusion of
these chlorpyrifos references by the commenters.
    The Agency believes that direct comparison between the results of
studies with chlorpyrifos and carbofuran should be done with great
caution. OP and NMC insecticides have different time courses of
effects, which lead to toxicity profiles that are somewhat different.
The studies cited by the commenters (Padilla et al., 2005, Marable et
al., 2007) involve long-term treatment (chronic exposure) in adult
animals where blood, brain and peripheral tissue AChE inhibition were
at steady-state. The time course and AChE inhibition in various tissues
at steady state is distinctly different from acute AChE inhibition at
the time of peak effect, like that in the carbofuran studies. In the
case of acute toxicity with NMCs, the time course of inhibition and
reactivation of the AChE is rapid (minutes to hours). In the case of
OPs, when steady state inhibition is achieved in adults, recovery is
slow (days to weeks) and is influenced by synthesis of new AChE
protein. In addition, as stated above, responses in adults are not
adequate for drawing conclusions in the young. As such, the Agency
views the Padilla et al., (2005) and Marable, et al., (2007) references
as providing limited useful information for the carbofuran risk
assessment.
    Although the Agency is cautious about direct comparisons between
OPs and NMCs, it must be noted in this case that: (1) The commenters
have provided an incomplete review of the literature and ignored more
relevant studies; and (2) the chlorpyrifos literature does, in fact,
generally support the Agency's conclusions with respect to carbofuran.
    The commenters state specifically that ``[t]here is also evidence
that RBC AChE activity can be inhibited to a greater degree than AChE
in peripheral organs.'' The assertion that RBC AChE activity can be
more inhibited than peripheral tissues ignores relevant chlorpyrifos
data. For example, Richardson and Chambers (2003) showed that lung AChE
can be more sensitive than serum and brain AChE in rat fetuses (Ref.
82).
    EPA's response to comments document provides a more extensive
review of chlorpyrifos studies (those that include data in peripheral
tissue) than that discussed by the commenters (Ref. 112). While there
are many studies that have measured AChE inhibition with chlorpyrifos,
the Agency has limited its discussion here only to those in pregnant
rats and fetuses which provide peripheral AChE data (e.g., heart, lung,
and liver) as they are the most relevant to the present issues raised
by the commenters. Several chlorpyrifos studies in pregnant dams and/or
their fetuses show that peripheral AChE is more sensitive than brain
AChE. For example, a study conducted by Dow AgroSciences showed that a
dose of 1 mg/kg results in 4-6 fold more inhibition in heart AChE than
in brain tissues (Refs. 66 and 67). Similarly, Hunter et al., (1999)
showed that in pregnant dams at doses of 3 mg/kg liver AChE was
inhibited 84% when brain tissues were inhibited by only 41% (Ref. 51).
Fetuses evaluated at or near the peak time of effect in the Hunter et
al., (1999) study showed 2-8 fold more AChE inhibition in liver than in
brain. (Id.). Although there is some variation among studies, the
preponderance of data supports the

conclusion that peripheral tissues are more sensitive to chlorpyrifos
exposure than brain tissues. Thus, the chlorpyrifos data in fetuses and
pregnant rats supports the Agency's concern that sole reliance on brain
data may not be protective of the PNS following carbofuran exposure.
Chlorpyrifos data in post-natal pups are described in the Agency's
Response to Comments on the proposed tolerance revocation (Ref. 112).
    Although OPs and NMCs both inhibit AChE, the chemical reaction at
the active site differs. This difference leads to different time
courses of toxicity and recovery. As such, comparisons, particularly
quantitative ones, between chlorpyrifos and carbofuran should be done
with care. However, in general, review of these data supports the
Agency's conclusion for carbofuran that in the absence of high quality
data that is relevant for risk assessment in either peripheral tissue
or a surrogate (i.e., RBCs), the Agency cannot be certain that brain
AChE inhibition is protective of potential peripheral toxicity
following carbofuran exposure. Therefore, the chlorpyrifos data support
the Agency's conclusion that at least a portion of the children's
safety factor must be retained for carbofuran given the lack of
peripheral AChE data and lack of RBC AChE (as a surrogate for
peripheral AChE) at the low end of the dose-response curve.
    b. Comments relating to EPA's approach to deriving the 4X factor.
One group of commenters argued that EPA's approach to calculating its
4X Children's Safety Factor was flawed. According to the commenters, it
would be more plausible and straightforward to compare the RBC and
brain AChE levels at the same time in the same rat when these rats are
exposed to carbofuran. Based on an analysis of the RBC and brain AChE
inhibition data, the commenters' claim that the percentage reduction in
RBC AChE in a rat is almost the same as the percentage reduction in
brain AChE in that same rat. The commenters summarize a statistical
evaluation of the experimental data on AChE inhibitions in RBC and
brain in rats due to carbofuran exposure conducted by their contractor,
and claim that this evaluation shows that the percentage inhibition of
RBC AChE in a rat compared to the percentage inhibition of brain AChE
in the rat is no more than 1.5X--a difference that they claim is not
meaningful from a physiological perspective and does not warrant
imposition of a 4X FQPA safety factor.
    EPA notes that the commenters recommended this approach of
comparing the degree of inhibition for each animal as part of their
presentation to the Carbofuran SAP. EPA also addressed this approach,
comparing RBC to brain in the same animals, at the SAP and in the
responses to the SAP report (Ref. 109). It is notable that the SAP did
not endorse this approach.
    EPA's analyses of the commenters' approach identified several
significant deficiencies. First, the comparison suggested by the
commenter means that EPA would need to ignore existing data. This is
because only EPA's study of PND11 animals contains both brain and RBC
data, so the comparisons suggested by the commenter can only be made
using that dataset. However, the dose levels in that study were so high
that the lower portion of the dose-response curve was missed. At these
higher doses, there is little difference between the levels of brain
and RBC inhibition. This phenomenon, namely the relative sensitivity of
RBC compared to brain appears smaller at higher doses. This phenomenom
is also shown in multiple chlorpyrifos studies, where blood or
peripheral measures of AChE inhibition are more sensitive than brain at
low to mid doses but the tissues appear to be similar at higher doses.
    Second, the commenters' approach is fundamentally flawed. The
commenters' suggested alternative relies exclusively on comparisons
between the degree of inhibition in the treated animals without any
regard to the doses at which the effects occurred. For example, one
animal may have shown, on average, 10% inhibition in the brain, when it
demonstrated 20% RBC inhibition. Under this approach, what would be
relevant would simply be the ratio of 1:2. But the Agency believes it
is critical to focus on the ratios of potency, which is the ratio of
the doses in the data that cause the same level of AChE inhibition. The
Agency's approach of comparing potencies is more directly relevant for
regulatory purposes than comparisons of average inhibition. This is
because dose corresponds more directly to potential exposures, which is
what EPA regulates (i.e., how much pesticide residue does a child
ingest). By comparison, the commenters' suggested reliance purely on
the average degree of inhibition provides no information that
corresponds to a practical basis for regulation.
    Finally, the range of ratios of effects that the commenters propose
as an alternative is consistent with range of potencies that EPA has
calculated at the higher doses in the available data, so the
commenters' results do not ultimately contradict EPA's assessment,
which tries to account for what occurs at lower doses. Briefly, if the
dose-responses for RBC and brain inhibition were linear, ratios of
inhibition would equal ratios of BMDs. However, these dose-responses
are not at all linear, and the available data demonstrate that brain
and blood dose-responses have somewhat different shapes. Thus,
estimates of relative effects at particular, relatively high, doses are
not relevant to the problem of estimating potency ratios at lower
doses. The dose-response curves level off at about the same level of
inhibition, so, at high doses, there is no difference between the ratio
of inhibitions. Except at the lowest dose, where the ratio is slightly
greater than 2, the remaining ratios are only slightly greater than 1.
Given the inevitable statistical noise in these measures, it is clear
that the ratios expected from EPA's modeling are substantially similar
to what the commenter finds in its comparison between individuals.
Accordingly, the commenter's suggested comparisons at higher doses
provide no evidence of what occurs at lower doses; and thus provides no
evidence that demonstrates that EPA's modeling results at lower doses
is inaccurate.
    One group of commenters claimed that the statistical comparisons
that support EPA's selection of a 4X children's safety factor are
flawed. The commenters claim that, even assuming that RBC values are
relevant, EPA's conclusion that RBC effects in the relevant studies
were four times more sensitive than brain effects is not mathematically
supportable. The commenters reference statistical analyses performed
for them by a contractor, which they claim show that EPA's calculation
of the 4X children's safety factor is simply incorrect. The commenters
complain that the datasets EPA used for brain differ not only because
they were from different studies, but also because the data were taken
at different times ranging from 15 minutes to 4 hours after dosing. The
commenters also raise the concern that EPA's decision to combine data
for different strains of rats, sexes, experiments, laboratories, dates,
dose preparations, rat ages, and times between dosing and AChE
measurement, is problematic, claiming that these differences in study
design severely limit the validity of EPA's comparisons. In addition,
the commenters claim to have found a number of errors and
inconsistencies in how the modeling was conducted. Correcting for these
errors, the commenters claim, shows that the

BMDs for brain and RBC data are essentially the same.
    As discussed at length below, and in EPA's Response to Comments
document, EPA disagrees that its statistical modeling was in any way
flawed (Ref. 112).
    In general, EPA believes that consideration of all available data
is the scientifically more defensible approach, rather than the
selective exclusion of reliable data. The Agency's Draft BMD Guidance
says the following: ``Data sets that are statistically and biologically
compatible may be combined prior to dose response modeling, resulting
in increased confidence, both statistical and biological, in the
calculated BMD'' (Ref. 100). The Agency's carbofuran analysis has
included all available, valid data in its analysis. Further regarding
combining data from multiple strains, the SAP was fully aware that the
Agency was planning to derive BMD estimates from data sets using
different strains of rats (Ref. 43).
    By contrast, the commenters' suggested analysis ignores relevant,
scientifically valid data. The FMC analysis left out the 30-minute data
from MRID no. 47143705. The commenters have provided no rationale as to
why it would be appropriate to selectively exclude data from the time
frame in this study most relevant to the risk assessment (i.e., peak
AChE inhibition). The commenters' analysis of the individual datasets
from MRID no. 47143705, showed that at 30 minutes the females and males
provide BMDL10s of 0.009 mg/kg/day and 0.014 mg/kg/day,
respectively. When the datasets were combined, inclusion of the 30-
minute timepoint from MRID no. 47143705 decreased the BMDL10
from 0.033 mg/kg/day to 0.030 mg/kg/day.
    EPA has used a sophisticated analysis of multiple studies and
datasets to develop the PoD for the carbofuran risk assessment.
However, instead of this analysis, EPA could simply have followed the
general approach laid out in its BMD policy (Ref. 100), which is used
in the majority of risk assessments. Under this general approach, EPA
would regulate using the most sensitive effect, study, and/or dataset.
If the Agency chose not to combine the data in its analyses, as the
commenters' suggested, data collected at or near the peak time of
effect (i.e., 30 minutes) would in fact provide the more relevant
datasets. If this more simple approach were taken, in accordance with
BMD guidance, EPA would select the lowest BMDL10. Assuming
the commenters' values were used, EPA would have selected a PoD of
0.009 mg/kg/day, instead of 0.03 mg/kg/day, which is the value EPA is
currently using in its risk assessment.
    Further, the commenters complain that EPA's approach of combining
data across multiple studies is scientifically inappropriate. The
commenters have, however, combined the results of analysis from four
datasets. It is notable that most of the issues cited by the commenters
also apply equally to the commenter's own analysis, as described in
more detail in EPA's Response to Comments document (Ref. 112).
    EPA has addressed all of the commenters' claimed inconsistencies in
its Response to Comments document (Ref. 112). The majority of these
claimed flaws and inconsistencies were either misunderstandings by the
commenters or areas where it was the commenters who were incorrect, not
EPA. However, in response to some of their allegations, EPA conducted
new analyses to determine whether the suggested alternative approaches
would make any significant difference in EPA's modeling outcomes. For
example, in response to one of their comments, EPA used the dose-time-
response model to extrapolate BMD50s to develop a common
point of comparison between all studies. Specifically, EPA extrapolated
the PND11 brain analysis to estimate BMD50 for 40 minutes
after dosing for comparison with the existing PND11 RBC
BMD50, and extrapolated the PND11 RBC BMD50 to 15
minutes after dosing for a range of assumed recovery half-lives, for
comparison to the existing PND11 brain BMD50 (Refs. 30 and
31). In either approach, the estimate of the RBC to brain potency ratio
in PND11 animals is increased, and EPA's safety factor would
correspondingly increase to reflect that larger difference. For
example, when the PND11 brain BMD50 is extrapolated to 40
minutes, the RBC to brain potency ratio grows to 4.7 (Ref. 30), and
when the PND11 RBC BMD50 is extrapolated to 15 minutes,
using a range of estimates for the recovery half-life of the RBC
endpoint, the RBC to brain potency ratio ranges from 4.2 to 4.6 (Ref.
31). The commenter's approach would therefore support a children's
safety factor of 5X rather than 4X.
    Similarly, in response to the complaint that EPA should have
generated a new dose-response model in order to calculate the
BMD50s for brain and RBC, EPA conducted the suggested
calculation (Ref. 112). The ratio of brain to RBC BMD50s in
this new analysis is the same as that calculated by EPA using the
mathematical expression. Both provide a ratio of brain to RBCs
BMD50 of 4X. Specifically, the values are for PND11 brain
BMD50 0.35 and for RBC, 0.086, resulting in a ratio of 4.09
(Ref. 112).
    Several commenters disagreed with the Agency's decision to apply a
4X, arguing that the high bar set by the statute for lessening the
tenfold safety factor has not been achieved because ``important data
gaps exist.'' These commenters raised the concern that key data on
carbofuran toxicity and exposure for the very young are inadequate.
Examples include: No data were presented for pre-natal sensitivity as
would have been desirable for addressing the need to protect developing
individuals; BMD10 estimates from the available RBC AChE
inhibition data are not reliable due to lack of data at the low end of
the dose response curve. The commenters also highlighted EPA's
assumption that the RBC and brain AChE dose response curves are
parallel, noting that there are currently no data to test this
assumption for carbofuran. One commenter raised the concern that ``EPA
has no substantial research on alternate mechanisms of carbofuran
toxicity. EPA has acknowledged but failed to incorporate in its
assessment the potential for lasting adverse effects from transient
exposures during fetal and newborn life-stages, and EPA has
acknowledged that there are uncertainties in the available data (as
raised by the SAP).'' The commenters concluded that the Agency does not
have the requisite ``completeness of data'' required by law to lessen
the safety factor,'' and urged the Agency to reinstate the default 10X
safety factor.
    Section 408(b)(2)(C) of the FFDCA requires that EPA consider the
``completeness of data with respect to exposure and toxicity to infants
and children'' when evaluating whether retention of the default 10X
safety factor is appropriate. The Agency has concluded that available
exposure information is sufficient for purposes of developing its human
health risk assessment, and has adequately accounted for the lack of
certain hazard information with the retention of a 4X children's safety
factor. Moreover, the Agency has concluded that the exposure assessment
does not substantially underestimate food or water exposure. The
completeness of the hazard database and the interpretation of available
toxicity studies were described elsewhere in this final rule preamble.
The Agency continues to believe that a 4X children's safety factor is
appropriate for carbofuran.
    Several commenters alleged that application of a 4X children's
safety factor, rather than a 10X, is inconsistent with the SAP's
advice. These

commenters argued that the SAP report reflected strong support, if not
unanimity, among panel members for a safety factor of at least
fivefold, and pointed to the statement in the report that ``some Panel
members considered it reasonable to retain the full 10X [children's]
safety factor (Panel Scenario 5). Given the uncertainty in the data and
in its interpretation for risk assessment by the entire Panel, these
Panel members believed that this standard for change had not been
met.''
    As described in detail in the Agency's response to the SAP report
(Ref. 109), the Agency believes there was a general consensus that a
children's safety factor of 2X or greater was necessary. The Agency
does note that one Panel member thought a 1X was appropriate and at
least two believed a 2X was appropriate. Given that the Panel did not
take a vote on the record and the report notes that the Panel did not
endorse a particular approach, any conclusions about the possible
``unanimity'' of the Panel is speculation. However, as described in the
Agency's response to the SAP and in the July 2008 proposed rule, EPA
believes that on balance, its reliance on the data derived factor of 4X
is consistent with the SAP's advice, as a whole.
    Several commenters raised concern that EPA's application of a 4X
children's safety factor did not adequately account for the differences
between children and adults. The commenters raised several reasons that
children are more vulnerable than adults to carbofuran. These include
the following:
    (1) Children are growing. Pound for pound, children eat more food,
drink more water and breathe more air than adults. Thus, the commenters
conclude, they are likely to be more exposed to substances in their
environment than are adults. Children have higher metabolic rates than
adults and are different from adults in how their bodies absorb,
detoxify and excrete toxicants.
    (2) Children's bodies, including their nervous, reproductive,
digestive, respiratory and immune systems, are developing. This process
of development creates periods of vulnerability. Exposure to toxicants
at such times may result in irreversible damage when the same exposure
to a mature system may result in little or no damage.
    (3) Children behave differently than adults, leading to a different
pattern of exposures to the world around them. For example, they
exhibit hand-to-mouth behavior, ingesting whatever substances may be on
their hands, toys, household items, and floors. Children play and live
in a different space than do adults. For example, very young children
spend hours close to the ground where there may be more exposure to
toxicants in dust, soil, and carpets as well as low-lying vapors.
    (4) The recovery time from carbofuran exposure for the very young
is more than four times that of adults, as the SAP noted.
    Carbofuran does not have any residential uses. As such, comments
about the breathing rate of children and hand-to-mouth behavior do not
apply to carbofuran's risk assessment. The Agency agrees with the
commenters that infants and children represent a potentially
susceptible lifestage to carbofuran exposure. Accordingly, the Agency
has taken steps to incorporate lifestage specific information in its
risk assessment. For example, the Agency's hazard assessment has used
data from PND11 rat pups as the PoD in extrapolating human risk.
Although it is not possible to directly correlate ages of juvenile rats
to humans, PND11 rats are believed to be close in development to
newborn humans (Refs. 5, 12, and 26). The Agency's food exposure
assessment relies on DEEM-FCID\TM\, which uses the CSFII database,
including the 1998 supplemental survey of children. As such, the
Agency's aggregate risk assessment accounts for the decreased metabolic
capacity of juveniles in addition to age-specific behaviors in eating
and drinking.
    One commenter noted that while they agreed that the use of brain
and RBC AChE inhibition data is an appropriate endpoint for use in
EPA's risk assessment, they did not believe that it is sufficiently
health-protective to only rely on this endpoint without an uncertainty
factor because it has not been established scientifically that AChE
inhibition is the most sensitive endpoint. The commenter noted that one
SAP member argued for retaining a 10X children's safety factor because
of uncertainty in both the dosimetry in subtle developmental effects
and also the available data on related pesticides suggesting effects on
nerve outgrowth at cholinesterase inhibition levels of 20% or less, and
some effects at less than 10%. The commenter asserted that ``this
position is supported by published studies on the toxicity of a related
family of pesticides, the OPs, reporting that exposures during fetal
and newborn life-stages affect diverse cellular functions by mechanisms
of toxicity that are independent of cholinesterase inhibition, and may
occur at exposures that elicit less than 20% inhibition (Refs. 1, 2,
32, and 91). This is important because while the systemic toxicity that
results from cholinesterase inhibition is reasonably well
characterized, it does not explain why rodents exposed pre- and post-
natally seem to recover from cholinesterase inhibition relatively
rapidly, yet display persistent and more severe damage to the central
nervous system'' (Ref. 90). The commenter also pointed to what they
assert is a ``growing body of science for OPs demonstrating that non-
cholinergic mechanisms of toxicity may be acting to disrupt multiple
brain targets'' (Ref. 80). According to the commenter, experts have
warned that ``the fact that alterations in neurodevelopment occur with
OPs below the threshold for cholinesterase inhibition reinforces the
inadequacy of this biomarker [cholinesterase inhibition] for assessing
exposure or outcome related to developmental neurotoxicity'' (Ref. 92).
When reviewing the EPA assessment of the OPs, the commenter asserted
that the FIFRA SAP in 2002 had raised the same concern, stating that
``reliance on a single biochemical assay to measure brain damage may
become problematic'' (Ref. 41).
    The Agency is aware of the available studies noted by the
commenters on the OPs and has recently developed a draft issue paper on
many such studies as part of its on-going review of chlorpyrifos. The
Agency cautions the commenters against extrapolating these studies to
the NMCs. The Agency is not aware of any studies in laboratory animals
where long-term behavioral or other effects were noted with exposure to
NMCs. Moreover, the Agency is not aware of any epidemiology study that
has associated NMC exposure with adverse birth or neurodevelopmental
outcomes in children. Although OPs and NMCs both inhibit AChE, the
chemical reaction at the active site differs. This difference leads to
different time courses of toxicity and recovery. Time to peak effect
and time to recovery for the NMCs is very rapid in comparison to OPs.
Moreover, once reactivation of the AChE occurs, the parent compound is
no longer active. As such, NMCs may not be present in the body long
enough to cause the types of outcomes associated with OP exposure. The
Agency concludes that there are no data which link NMC exposure,
including studies with carbofuran, at relatively low doses to long-term
outcomes in juvenile animals or children. Therefore, the Agency further
concludes that the OP studies noted by the commenters have limited
relevance to the carbofuran human health risk assessment.
    c. Comments regarding consistency in approach. One group of
commenters

claimed that the derivation of carbofuran's PoD and children's safety
factor was inconsistent with EPA's analyses for other NMCs, including
aldicarb and carbaryl.
    The commenters are incorrect. The Agency's recent hazard
assessments of carbaryl and aldicarb are each consistent with OPP
policies and practice, as well as with the Agency's approach to the
assessment of carbofuran.
    The commenters' assertions regarding aldicarb were based on an
earlier assessment. At the time the Agency conducted the assessment to
which the commenters refer, the Agency was unaware of the differences
in sensitivity between PND17 and PND11 animals. Since EPA became aware
of the differences, EPA has required the aldicarb registrant to conduct
a CCA study in PND11 rats; the Agency anticipates the receipt of this
study and the companion range-finding and time course studies in 2009.
In the absence of these data, EPA will apply the statutory default
children's safety factor to account for the additional sensitivity of
PND11 animals, because the Agency lacks any data that could be used to
derive a reduced factor that EPA could determine will be ``safe for
infants and children.''
    Carbaryl was not evaluated any differently than carbofuran. EPA's
typical practice which was used in both the carbofuran and carbaryl
risk assessments, is to use the central estimate on the BMD to provide
an appropriate measure for comparing chemical potency and to use the
lower limit on the central estimate (i.e., BMDL) to provide an
appropriate measure for extrapolating risk. This approach is also
consistent with the NMC cumulative risk assessment (CRA) and single
chemical risk assessments for multiple OPs.
    In the case of carbaryl, the commenters inappropriately focused on
the BMDL10s, instead of the BMD10s. The more
appropriate comparison is between the BMD10s; the carbaryl
brain BMD10 is 1.46 mg/kg/day compared with the RBC
BMD10 of 1.11 mg/kg/day. As such, the brain to RBC ratio is
1.3X. Therefore, for carbaryl, the brain and RBC AChE data are
similarly sensitive, and, when the tissues are similarly sensitive, the
Agency prefers to use data from the nervous system tissue (i.e., brain)
over data from a surrogate tissue (i.e., RBC) (Ref. 108). Thus, for
carbaryl, the RBC AChE inhibition (a surrogate for PNS AChE inhibition)
and brain AChE inhibition were basically equivalent. This contrasts
with the situation with carbofuran where a significant difference in
AChE inhibition between the two is noted.
    With regard to the carbaryl children's safety factor, the available
brain and RBC dose-response data in PND11 pups include data from the
lower end of the dose-response curves. ORD's comparative AChE data with
carbaryl show that at the lowest dose at or near 20% inhibition in
brain and RBC AChE was observed. Although not ideal, the carbaryl data
provide information closer to the benchmark response of 10%, which
allows for a reasonable estimation of the BMD10 and
BMDL10. This is distinctly different from ORD's data with
carbofuran in PND11 and PND17 pups where 50% or greater RBC AChE
inhibition was observed at the lowest dose.

C. Comments Relating to EPA's Exposure Assessment

    1. Food exposures. One group of commenters alleged that it is more
appropriate to apply USDA PDP residue monitoring data from winter
squash to pumpkins, rather than residue data from cantaloupes.
    The Agency agrees with the commenters. An appropriate residue
assignment has been made in the latest dietary exposure assessment
(Ref. 71). The results of this assessment are discussed below in Unit
VIII.E.1.b.
    One group of commenters asserted that the measurable residues of
carbofuran in milk obtained by the USDA PDP program should be
``adjusted to a lower level because a significant proportion of the
milk residues in the PDP database are due to carbofuran use on alfalfa,
which is no longer permitted under the carbofuran label.'' The same
commenters discussed the results of an exposure assessment that they
apparently conducted, in which they have reduced the residues
anticipated to be found in milk by some unspecified amount.
    Based on the commenters' results, their adjustments to milk
residues appear to have about a 50% reduction on the risk estimates for
the food only results. While the commenters appeared to have made the
adjustments to milk residues in most of their food-only assessments, as
well as their food+water assessment, they did not: (1) Describe the
amount by which residues were reduced; (2) present the DEEM-FCID\TM\
input files detailing the residue inputs used in their assessment; or
(3) provide to the Agency related data to support any such reduction
factor--information that the Agency would need to accept such an
adjustment. Because of the lack of any explanation or rationale, the
Agency attempted to determine how the commenters made the ``adjustment
to residues'' to account for the cancellation of use on alfalfa. As
described in the Agency's Response to Comments, EPA was not able to
reproduce the commenters' results, but did approximate their reported
results after reducing milk residues by 77% (Ref. 112).
    In actuality, it is difficult to ascertain how the recent
cancellation of carbofuran use on alfalfa may affect future residues
found on milk (from dairy feed items associated with corn, potatoes or
sunflowers). This is especially true for milk since it is a blended
commodity. That is, milk may be obtained from dairy cows from multiple
farms (i.e., a dairy cooperative). The milk in any particular PDP
sample may have come from dairy cows that might have had a diet that
contained substantial amounts of alfalfa, or a diet that contained
predominately corn, or from multiple farms using various combinations
of feed that may or may not have been treated with carbofuran. In any
case, the aggregate pesticide use statistics do not support the
contention that most residues in milk are (or have been) due to
carbofuran use on alfalfa--the USDA and Proprietary use data indicate
that field corn has historically had a greater overall amount of total
carbofuran use than alfalfa. Potatoes and sunflowers rank 3rd and 4th.
    The Agency included a summary of dietary burdens for dairy cattle
in the dietary exposure analysis memorandum documenting the higher
dietary burden involved with field corn feed stuffs (Refs. 70 and 71).
These two diets represent a corn-based diet and an alfalfa-based diet,
accounting for appropriate amounts of roughage and protein. Based on
these dietary burdens, milk from dairy cows having a corn-based diet
may have higher concentrations of carbofuran than milk from cows having
an alfalfa-based diet (Refs. 70 and 71).
    The Agency notes that 3-hydroxy carbofuran was detected in about
7.5% of all PDP milk samples analyzed in 2004 and 2005 (7.5% = 110
detects in 1,485 samples).
    Considering all of the various factors involved with the PDP milk
samples-e.g., uncertainty regarding mixture of feeds, pesticide use and
corresponding residues--the Agency finds no basis for applying
estimated reduction factors to actual measured concentrations of
carbofuran residues found by the PDP program in milk based on the
cancellation of alfalfa uses. In the absence of supporting data the
Agency has no scientific basis for making the

commenters' recommended changes to the dietary exposure assessment with
regard to carbofuran residues in milk. Certainly, the commenters' have
failed to provide any scientific justification for their position.
Moreover, since the Agency was unable to reproduce the commenters'
results, EPA could not make the suggested adjustment, even if they had
provided details on the exact adjustment figure they wanted EPA to
apply.
    One group of commenters raised concern that PCT estimates used by
the Agency for bananas, potatoes, and milk are conservatively high.
    In response to those comments, the Agency reviewed its PCT
estimates for the two crops and revised its PCT estimates for bananas
from 78% to 25%. The Agency also developed a regional PCT estimate for
potatoes of 5% based on projected limited use in the Northwest, and has
applied these estimates in its revised dietary risk assessment (Ref.
71). The Agency also applied a 5% CT for milk, based on the PCT for
potatoes, which is the feed stuff with the highest PCT. Further
discussion regarding the Agency's previous and revised PCT estimates
can be found in References 71 and 122. As discussed below in Unit
VIII.E.1.b., these adjustments had relatively modest effects on the
dietary exposure assessment of those crops the registrant now seeks to
maintain.
    Some commenters claimed that the Agency acted inconsistently in the
way in which it conducted its ``Eating Occasion Analyses'' to account
for the extent to which individuals recover from AChE inhibition
between exposure events. The commenters claimed that the Agency
analyzed aldicarb and carbofuran differently, and came to different
conclusions concerning the effects of reversibility for these two
compounds.
    The commenter's assertion that the Agency came to different
conclusions concerning the effects of reversibility for aldicarb and
carbofuran is incorrect. EPA discusses the Eating Occasion Analysis it
conducted for carbofuran in greater detail in Unit VIII.E.3. below and
in its Response to Comments document (Ref. 112).
    The Agency concurs with the commenter that ``there is no basis for
treating aldicarb-treated potatoes differently from carbofuran treated
potatoes.'' The commenters' assertions regarding what the Agency has or
has not done with respect to the Eating Occasion Analysis (i.e.,
``reversibility'') to some extent reflects confusion resulting from the
several assessments the Agency has produced since 2006. Since that
period, EPA has conducted several risk assessments, based on the
tolerances FMC has variously indicated that it wished EPA to retain.
EPA notes, for clarity, that for the proposed rule, EPA conducted a
risk assessment of ``all registered carbofuran uses'' that did
incorporate the concept of reversibility (i.e., ``persisting dose'').
The proposed rule also contained an assessment of the subset of ``6
domestic uses'' that EPA believed the registrant primarily wished to
retain, which did not incorporate this concept because these were not
the only crops on which carbofuran was legally permitted to be used.
However, now that the registrant has cancelled all but four domestic
food uses, the Agency's risk assessment of all the remaining uses
accounts for reversibility, performed using the same DEEM-based Eating
Occasion Analyses previously used for both carbofuran and aldicarb.
    In support of their contention, the commenters took an observation
in the aldicarb IRED that exposures did not pass at the per capita
99.9th percentile, but were equal to the aPAD at a lower percentile--
out of context, and used that statement to infer that the Agency
regulates at this lower percentile. This is incorrect. The aldicarb
registrant agreed to a number of risk mitigation measures that brought
the aggregate risks to below the aPAD at the 99.9th per capita
percentile. The registrant agreed to modify the aldicarb label to
require a 500-foot well set back for aldicarb use on peanuts (GA soil
type), since aggregate exposure at the per capita 99.9th percentile for
infants continued to exceed the level of concern even after
reversibility was accounted for in the Eating Occasions Analyses under
the 300-foot well set back scenario.
    In summary, the Agency did not analyze aldicarb exposure and risk
any differently than it analyzed carbofuran exposure and risk; the
``persisting dose'' concept was used in both assessments.
Mathematically and conceptually, the calculations of the adjustment for
reversibility are the same for both exposure assessments. Any
differences in the conclusions EPA drew from the analyses are
attributable purely to the factual differences between the two
compounds. The reduction in ``persisting dose'' is slightly greater for
aldicarb due to its quicker recovery times (2-hour half-life for
aldicarb), but in both cases, the Agency applied the same procedure to
account for reversibility. The qualitative results for the food only
and food + water scenarios presented in Unit VIII.E., produce similar
qualitative results: in both cases, accounting for reversibility
between eating occasions for food alone results in relatively modest
reductions in the ``persisting dose'' at the per capita 99.9th
percentile, and a relatively large effect on exposure for water alone,
or food+water, when water is the predominant contributor (73 FR 44864).
These Eating Occasion Analyses support the Agency's position that
reversibility has a relatively greater effect for drinking water
exposures than for food exposures.
    One group of commenters claimed that the Agency should have
calculated the effects of carbofuran exposure based on the ``persisting
dose'' over the 1,440 person-minutes rather than on the person-days
that are currently used by the Agency.
    In effect, the commenters suggest that the ``persisting dose''
should be calculated over the entire 1,440 minutes of each modeled
person-day (1,440 minutes/day = 24 hrs x 60 minutes/hr). EPA has
rejected this approach for a number of reasons. While the commenters'
person-minute approach may be an attempt to capture multiple measures
with one statistic, it does not properly capture the Agency's concern
regarding peak inhibition, and the commenters' assertion that the
Agency should use all person-minutes to calculate the per capita 99.9th
percentile is misguided at best since: (1) It does not reflect a
comparison to peak inhibition which is what the Agency believes is the
most appropriate and relevant toxicological measure and (2) it produces
risk estimates that are entirely dependent upon the time of day at
which consumption occurs. Hence, this approach will obtain different
values depending upon the reported time of consumption even if exposure
occurs on a single eating occasion. The commenters suggested approach
does not appear to capture peak inhibition, or other temporal aspects
of cholinesterase inhibition (e.g., duration over which inhibtion
exceeds 10%). EPA's Response to Comments document provides a further
explanation of this issue and details why the Agency's approach is
consistent with the identified endpoint (peak inhibition) and the
corresponding point of departure (BMDL10 that serves as the
basis for calculating a %aPAD (Ref. 112).
    2. Drinking water exposures. As part of their comments on the
proposed tolerance revocation, FMC submitted a revised label with use
restrictions intended to address drinking water contamination. These
measures include eliminating a number of crop uses, prohibiting use in
a broad swath of areas with potentially vulnerable soils, and

requiring application buffers in other areas. In addition to these
label modifications, the registrant, along with two other commenters,
submitted comments summarizing the results of risk assessments they had
previously submitted, and the results of new risk assessments they
claim to have conducted. The commenters did not provide to the Agency
either the new risk assessments they claim to have conducted, or the
underlying support documents for those assessments, including the
``national leaching assessment'' or the ``crop-specific evaluation of
use patterns and the registrant's proposed non-application buffers
using the PRZM-EXAMS model.'' FMC concludes that their label revisions
have a pronounced effect on dietary risk and result in ``exposure that
even fit within the risk cup that EPA has proposed.''
    EPA has reviewed the September 2008 proposed label modifications,
and a synopsis of the Agency's conclusions are summarized below in this
Unit. More detailed analyses can be found in EPA's Response to Comments
(Ref. 111). In addition, EPA's revised risk assessment, discussed below
in Unit VIII.E., is based on this revised label.
    The label revisions leave two national food uses on the label, corn
and sunflowers, and two regional food uses, potatoes in the northwest
and pumpkins in the southeast. EPA has assessed the impact of all of
these remaining uses, taking into consideration all label restrictions,
and has concluded that remaining uses may result in concentrations in
some locations that are similar in magnitude to those estimated
previously (Refs. 57, 58, 60, and 62).
    a. Comments relating to EPA's ground water analyses. One group of
commenters alleged that ``[g]roundwater sources are vulnerable to
carbofuran leaching only under certain conditions, namely where
permeable soils (e.g., areas with soils greater than 90% sand and less
than 1% organic matter), acidic soil and water conditions, and shallow
water tables predominate (e.g., where ground water is less than 30
feet).'' The commenters claim that these conditions are rare in areas
where carbofuran is used. They further assert that in ``most states
where carbofuran is used, less than 2% of the entire surface areas
possess sandy soil texture'' and that ``low pH conditions are not found
in carbofuran use areas allowed under the registrant's amended label''.
    EPA disagrees that the commenter's specific criteria define 100% of
conditions where ground water sources are vulnerable to carbofuran
leaching. No comprehensive analysis was provided evaluating how they
reached this conclusion. Although these criteria appear on the revised
carbofuran label restricting use, the spatial extent of the label
restrictions is not provided. As discussed in greater detail in EPA's
Response to Comments, the information provided as part of FMC's
comments (primarily maps depicting areas identified as vulnerable) is
not sufficient to allow the Agency to evaluate their claim (Ref. 111).
For example, water table depth can vary with the time of the year,
depending on such factors as the amount of rainfall that has occurred
in the recent past, and how much irrigation has been removed from the
aquifer. It is difficult to determine how the depth to the water table
varies throughout fields, and the definition of a ``shallow'' water
table is indeterminate (e.g., less than 30 feet). Furthermore, the
vulnerability associated with depth varies with location; for example,
deeper aquifers may be more vulnerable in areas with greater
precipitation and rapid recharge.
    While the assertion regarding percent sand is in part true, it is
misleading. While many states have only small areas of sandy soils,
some states have quite extensive areas. For example, according to FMC's
own assessment of high use states (Ref. 8), Texas had 4.2% sand,
Michigan had 21.3% and Nebraska had 26.3%. In addition, this statement
implies that soils that are sandy textured define the universe of soil
textures that are vulnerable to leaching. It is possible that more
fine-textured soils, for example sandy loams or silt loams, could also
be sufficiently permeable to result in carbofuran leaching as it has
not been established how much of a reduction in leaching might occur as
texture becomes finer. Furthermore, finer textured soils tend to have
more cracks and root channels and thus are more prone to preferential
flow.
    EPA also disagrees that the commenters have provided sufficient
information to support their general claim that only high pH conditions
(pH above 7) exist in all the areas in which carbofuran could be used
under FMC's September 2008 revised label. There is considerable spatial
variability in pH conditions for both the subsurface and surface
environments. The pH has a large effect on the persistence of
carbofuran as, for more acidic conditions, the hydrolysis half-life
increases from 28 days at pH 7 to years or more at pHs less than 6.
Further, the results of EPA's corn ground water simulations (bounded by
the high and low pH values of the aquifer system underlying the
scenario location) showed that a relatively small (0.5) decrease in pH
from 7 to 6.5 resulted in an increase by 4 orders of magnitude in the
1-in-10-year peak concentration of carbofuran. EPA has presented its
assessment of the newly submitted label in its Response to Comments
document and these issues are addressed in more detail there (Ref.
111).
    Accordingly, the criteria the commenters suggest are not sufficient
to prohibit use in all areas that could reasonably be expected to be
vulnerable to ground water contamination from carbofuran use. EPA's
assessment identifies an example of one area where carbofuran use would
still be permitted on the proposed labels; an additional scenario for
the updated ground water modeling provided in Reference 111 was based
on this location in the south-central region of Wisconsin. This
scenario is in no way unique; EPA expects that other similar sites
exist in other locations where carbofuran could still be used across
the United States.
    One group of commenters claimed that the most recent label
modifications ``has ensured that carbofuran use will not occur in these
vulnerable areas by removing them from the label.'' They support this
by reference to a map of the carbofuran use areas in 2005, that
identifies counties with DRASTIC scores as high as that of the location
of the prospective ground water study (PGW study) conducted by FMC in
Maryland, defining that combination as vulnerable.
    DRASTIC is a USEPA model that was developed as a screening tool to
identify ground water resources that are ``generally vulnerable to the
release of contaminants at the surface * * *.'' (Ref. 6). The
commenters indicate that the map provided in their comments shows
counties ``identified as vulnerable,'' based on DRASTIC scores that
exceed 185, and 2005 carbofuran usage, although the map's level of
resolution is insufficient to provide more than a general impression of
the location of ground water classified as vulnerable. In FMC's
September 2008 label revisions, FMC expanded the areas where carbofuran
cannot be applied, apparently because of ground water concerns. The
specific criteria that FMC used to determine these further locations
were not provided to the Agency. Nevertheless, EPA does agree that
ground water in the Atlantic Coastal Plain is vulnerable, and that FMC
has restricted use in those areas.
    However, EPA does not agree with the premise that only locations
with DRASTIC scores as high as that of the location of the Maryland PGW
study are those that require mitigation. DRASTIC

scores as high as those identified by the commenters would indicate
that the site is located in a generally sensitive or vulnerable area.
The Agency agrees that the DRASTIC tool can be used to generally
identify areas that may be vulnerable to pesticide contamination.
However, DRASTIC is somewhat dated (1987), and better methods currently
exist that can take advantage of geospatial data at a more refined
level than the county level used here. FMC apparently agrees with this
criticism since they subsequently developed the ``National Leaching
Assessment'' as part of their comments on the proposed tolerance
revocation, to replace their earlier DRASTIC assessment.
    Importantly, EPA believes that FMC has used an inappropriate
criterion for determining whether a site is vulnerable-that it has the
same or greater vulnerability (based on a DRASTIC score greater than
185) as that of the Maryland PGW study site. The maximum concentration
at the Maryland PGW site, adjusted to simulate an application rate of 1
lb/acre, was 21 [mu]g/L this exceeds acceptable exposure thresholds by
factors of 10 to 20 (Ref. 71). Thus, sites that are less vulnerable
(e.g., deeper aquifer, high soil sand content, higher organic matter),
with lower DRASTIC scores, could still be prone to have carbofuran
concentrations exceeding acceptable exposures.
    Further, the commenters provide no detail on the specific data used
to generate their DRASTIC estimates. In footnote 39 of their comments
they indicate that ``Data to support these [DRASTIC] inputs were
primarily collected from state-wide, statistically designed studies
conducted by state and federal agencies (primarily the National Water
Quality Assessment Program (``NAWQA''), but also state surveys and
other state and federal agricultural data, where NAWQA data were not
available.'') Given EPA's general reservations about their approach,
EPA cannot conclude that the commenters' assessment is scientifically
supportable or useful, without information on the sources of the data,
the geographic scale of the data, or how that input data was prepared
for the analysis.
    One group of commenters assert that their ``assessments revealed
that the soils and water pHs are generally higher in those states in
the Midwest and Northwest where most carbofuran is used, providing
further confirmation that conditions that favor carbofuran leaching in
those areas do not exist.''
    Since the commenters have not provided all of the assessments they
appear to have conducted, EPA is unable to confirm whether their
assessments do in fact support their contention. However, as a general
matter, none of the previously submitted assessments provided a
comprehensive analysis of the distribution of soil and water pHs for
the Midwest, Northwest or any other region of the country where
carbofuran use would be permitted on the September 2008 label, nor have
the commenters provided such an analysis with their most recent
comments. Further, the available scientific information does not
support their contention.
    EPA examined readily available data with respect to ground water
and soil pH in order to evaluate the spatial variability of pH. Data
from the United States Geological Survey (USGS) and other readily
available sources do not necessarily encompass the entire range of
ground water pH values present within a state. This is especially true
for shallow ground water systems, where local conditions can greatly
affect the quality and characteristics of the water. Also, pH in a
water body can be higher or lower than the tabulated average values. In
addition, average ground water pH values for a given area do not truly
characterize the area's temporal and especially spatial heterogeneity.
This can be seen by comparing differences in pH values between counties
within a state, and noting that even within a county individual wells
will consistently yield ground water with either above- or below-
average pH values for that county. The ground water simulations in
Reference 111 Appendix I reflect variability in pH by modeling
carbofuran leaching in four different soil and subsurface pH conditions
(pH 5.25, 6.5, 7.0, and 8.7), representing the range in the aquifer
system in that area. This range also approximates the pH range of
natural waters in general. The results of the ground water simulations
for corn use showed that a relatively small (0.5) decrease in pH from 7
to 6.5 resulted in an increase in the 1-in-10-year peak concentrations
of carbofuran in ground water of 4 orders of magnitude.
    FMC summarized the results of their ``National Leaching
Assessment'' which used PRZM and ``databases specifically created to
provide access to all necessary inputs for a national scale PRZM
modeling.'' They claim that after accounting for the use prohibitions
on their September 2008 label, the maximum 1-in-10-year peak
concentrations in all potential carbofuran use areas is 1.2-1.3 ppb,
while expected concentrations in most areas covered by this assessment
are below 1.0 ppb. They claim to have modeled a single application to
corn at 1 lb/acre--which is the application rate on the September 2008
labels applicable to the rescue treatment on corn--and simulated ground
water recharge and lateral flow. They assert that their estimate that
1-in-10-year peak carbofuran concentrations will not exceed ``~1 ppb''
is consistent with EPA's NMC CRA.
    Neither the ``National Leaching Assessment,'' nor the ``National
Pesticide Assessment Tool'' upon which the assessment appears to have
been based, were submitted to EPA for review, therefore EPA cannot
comment further on the methodology for reaching these conclusions, or
indeed, whether the assessment actually supports their claims. Based on
the information provided, EPA cannot confirm or negate the assertion
that there is no overlap between use and all potentially vulnerable
ground water, as the information provided does not enable the Agency to
evaluate this claim.
    EPA's assessment of the impacts of FMC's September 2008 label
differs significantly from the commenters' summary conclusions; these
differences are addressed more completely in EPA's Response to Comments
document, and are based on application by FMC of unsupported factors
(Ref. 111).
    Part of EPA's assessment of ground water exposure for the proposed
tolerance revocation was based on simulation modeling using PRZM for
corn grown on the Delmarva Peninsula in Maryland receiving an annual
application of 1.0 lb/acre-1. The 1-in-10-year peak estimated drinking
water concentration (EDWC) was 30.8 [mu]g/L. FMC's assessment of the
same label resulted in their estimate of concentrations up to 22.7
[mu]g/L. The September 2008 labels prohibit application at sites in the
Atlantic Coastal Plain with similar vulnerability to the Delmarva site.
However, EPA believes that the study and the resulting scenario derived
from this study remain relevant for other areas with similar
conditions, where use remains. Based on the September 2008 labels, EPA
has concluded that there are locations in the United States where
carbofuran could still be applied, and in which ground water
concentrations are estimated to be high enough to cause concern. For
example, simulations of corn grown the central sands region of
Wisconsin had an estimated 1-in-10-year peak concentration of 16 [mu]g/
L at pH 6.5 and 284 [mu]g/L at pH 5.25, both of which are in the pH
range for aquifers in this area (Ref. 115). For higher pH's in that
area,

estimated carbofuran concentrations were generally close to zero.
    As noted the ``National Leaching Assessment'' has not been provided
to EPA for review, and consequently, the Agency cannot determine model
input parameters or check model algorithms. In many cases, model inputs
cannot be directly inferred from values in the available weather and
soil databases (e.g., NOAA SAMSON weather datasets, NRCS Soil Datamart)
(Refs. 75 and 93). Methods used by FMC to select or calculate values
for model input from these databases were not described. The only model
output provided was in map format. While maps are useful for
interpreting results, maps alone are insufficient for a thorough
evaluation of the assessment, in part because of their spatial
resolution. Further, the maps provided by FMC do not represent all
carbofuran use patterns. For example, Figure IV-2 on page 42 of FMC's
comments does not address the granular use patterns and proposed label
prohibitions.
    FMC contends that their results are consistent with the NMC CRA,
but this is untrue. The NMC CRA examined carbofuran at two sites,
northeast Florida and the Delmarva Peninsula. In Florida,
concentrations were found to be below levels of concern because of high
pH, but in Delmarva, both in corn and in melon scenarios EPA estimated
that 90% of daily concentrations could be as high as 20.5 and 25.6
[mu]g/L, respectively. These values are greater than the 1 [mu]g/L that
FMC claims is the maximum expected 1-in-10-year peak concentration. The
claim that EPA's modeling fails to address use patterns ``changing
naturally over time'' is ambiguous, and EPA cannot evaluate any inputs
included by FMC to address this in their own modeling, if indeed they
did so. Because of these deficiencies, EPA is unable to verify or
evaluate the results of FMC's analysis and can reach no conclusion on
its validity or utility.
    FMC asserts that ``EPA's approach is not consistent with the
Agency's treatment of other carbamates. For example, in the aldicarb
assessment, EPA used monitoring data to develop eight different region-
specific scenarios, `based on broad similarity in compound usage, crop
type or soil conditions', and taking a `single maximum sample result
detected within [each] region during the last 5 to 10 years to
represent ground water concentrations within that entire region.' The
Agency estimated drinking water concentrations for risk assessment
purposes by accounting for the effect of ground water mitigation
measures (i.e., setbacks).'' In footnote 53 of their comments, FMC
apparently quotes from the aldicarb IRED ``[H]igher residue values that
may have resulted from historical use if aldicarb in vulnerable areas
were excluded.''
    EPA disagrees with FMC's assertion that the carbofuran drinking
water exposure assessment was not consistent with other carbamates,
particularly aldicarb. In both cases, Tier 2 modeling, using the PRZM
and EXAMS models, was used to characterize surface water exposure and
in both cases available monitoring data were summarized. For
carbofuran, ground water exposure was characterized using a combination
of targeted and non-targeted monitoring data, a PGW study, and Tier 2
modeling, through the course of two RED chapters and several post-RED
drinking water exposure assessments. For aldicarb, two different ground
water exposure assessments were conducted for the initial and the final
IRED chapters. In the comment quoted above, FMC has described the
process used for the aldicarb risk assessment supporting the initial
aldicarb IRED dated May 12, 2006.
    The second aldicarb ground water exposure assessment supported the
revised dietary exposure assessment in February 2007 (Ref. 48). This is
a more refined assessment, which relies on simulation modeling for
ground water using PRZM in places vulnerable to ground water leaching
where aldicarb was used. While FMC has correctly quoted ``[H]igher
residue values that may have resulted from historical use of aldicarb
in vulnerable areas were excluded,'' the implication that this is
different from EPA's evaluation of carbofuran is not correct. For
example, the carbofuran IRED describes monitoring in New York where
carbofuran use was canceled in 1984, and where detections of carbofuran
continue. The carbofuran IRED did not use the high concentrations of
carbofuran measured in drinking water wells in that study, up to 178
ppb, which resulted from historical use of carbofuran. In both cases,
historical monitoring data were described (Refs. 10 and 47), but
endpoints used for ground water exposure assessment were only based on
monitoring relevant to use patterns current at the time of the
assessment. For aldicarb, the Agency utilized retrospective monitoring
data collected after 1990. For carbofuran, the most relevant monitoring
data set was the Maryland PGW study. Because of the design of that
study, results could be adjusted to represent current use patterns.
    The aldicarb assessment took into account the impact of well
setbacks on estimated concentrations in ground water modeling conducted
in 2007. The carbofuran modeling in EPA's most recent assessment also
took into account the impact of well setbacks on estimated
concentrations in ground water. Previous carbofuran assessments did not
assess the impact of well setbacks, as setbacks were not included on a
proposed carbofuran label until September 2008.