[Federal Register: November 18, 2009 (Volume 74, Number 221)]
[Rules and Regulations]
[Page 59607-59686]
[DOCID:fr18no09-8]

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Part II

Environmental Protection Agency

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40 CFR Part 180

Carbofuran; Order Denying FMC's Objections and Requests for Hearing;
Final Rule

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0162; FRL-8797-6]

Carbofuran; Order Denying FMC's Objections and Requests for
Hearing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Order.

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SUMMARY: In this order, EPA denies objections to, and requests for
hearing on, a final rule revoking all pesticide tolerances for
carbofuran under section 408(d) of the Federal Food, Drug, and Cosmetic
Act (FFDCA). The objections and hearing requests were filed on June 30,
2009, by the National Corn Growers Association, National Sunflower
Association, National Potato Council, and FMC Corporation
(``Petitioners'').

DATES: This final order is effective November 18, 2009.

ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2005-0162. To access the
electronic docket, go to http://www.regulations.gov, and search for the
docket number. Follow the instructions on the regulations.gov Web site
to view the docket index or access available documents. All documents
in the docket are listed in the docket index available in
regulations.gov. Although listed in the index, some information is not
publicly available, e.g., Confidential Business Information (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 (703)
305-5805.

FOR FURTHER INFORMATION CONTACT: Jude Andreasen, Pesticide Re-
evaluation 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?

    In this document EPA denies objections and hearing requests by the
National Corn Growers Association, National Sunflower Association,
National Potato Council, and FMC Corporation (``Petitioners'')
concerning EPA's final rule revoking all pesticide tolerances for
carbofuran. This action may also be of interest to agricultural
producers, food manufacturers, or pesticide manufacturers. 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. 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. Acronyms

    The following is a list of acronyms used in this order:

AChE--Acetylcholinesterase
aPAD--Acute Population Adjusted Dose
BMD--Bench Mark Dose
BMDL--Bench Mark Dose Level
CCA--Comparative Cholinesterase Assay
CNS--Central Nervous System
CRA--Cumulative Risk Assessment
CSFII--Continuing Survey of Food Intakes by Individuals
CWA--Clean Water Act
CWS--Community Water System
DEEM-FCID--Dietary Exposure Evaluation Model-Food Commodity Intake
Database
ECG--Electrocardiogram
EDWC--Estimated Drinking Water Concentration
EPA--Environmental Protection Agency
FACA--Federal Advisory Committee Act
FDA--Food and Drug Administration
FIFRA--Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA--Federal Food, Drug, and Cosmetic Act
FQPA--Food Quality Protection Act of 1996
HSRB--Human Studies Review Board
HUC-8--8-digit hydrologic unit code
IRED--Interim Reregistration Eligibility Decision
LD50--Lethal Dose for 50% of a population
LOAEL--Lowest Observable Adverse Effect Level
NAWQA--National Water Quality Assessment Program
NHEERL--National Health and Environmental Effects Laboratory
NMC CRA--N-Methyl Carbamate Cumulative Risk Assessment
NOAEL--No Observable Adverse Effect Level
NOIC--Notice of Intent to Cancel
NRDC--National Resources Defense Council
OP--Organophosphate
ORD--Office of Research and Development
PAD--Population Adjusted Dose
PCA--Percent Cropped Area
PCT--Percent Crop Treated
PDP--Pesticide Data Program
PND--Post-Natal Day
PNS--Peripheral Nervous System
PoD--Point of Departure
ppb--parts per billion
ppm--parts per million
PRZM-EXAMS--Pesticide Root Zone Model-Exposure Analysis Model System
RBC--red blood cell
RED--Reregistration Eligibility Decision
RfD--Reference Dose
SAP--Scientific Advisory Panel
SDWA--Safe Drinking Water Act
USDA--United States Department of Agriculture
USGS--United States Geological Survey
WARP--Watershed Regression for Pesticides

II. Introduction

A. What Action Is the Agency Taking?

    Exposure to the pesticide carbofuran resulting from existing legal
uses is unsafe--unsafe for the general

population, and particularly unsafe for infants and children. EPA
reached this conclusion in 2006 after an exhaustive multi-year review
of the data on carbofuran as part of its effort to determine whether
carbofuran should be reregistered under the Federal Insecticide,
Fungicide, and Rodenticide Act (``FIFRA''), and whether the tolerances
allowing carbofuran residues on certain foods met the revised safety
standard in section 408 of the FFDCA. This multi-year review included
multiple opportunities for public participation, including no less than
four formal public comment periods. Following EPA review of yet more
carbofuran data submitted by FMC, the carbofuran registrant, and the
review of EPA's science findings by the FIFRA Scientific Advisory Panel
(SAP)--an independent scientific peer review panel--EPA again reached
the same conclusion in its July 31, 2008 proposal to revoke the
carbofuran tolerances (73 FR 44864 (July 31, 2008)). In response to
this proposed revocation, FMC submitted comments challenging many of
EPA's science findings and also requesting the cancellation of the
registration of carbofuran on several crops and the restriction of
where, and the manner in which, carbofuran could be used in the United
States on its remaining registered crop sites. Finding FMC's science
arguments to be flawed and its proposed amendments to the carbofuran
registration to be insufficient, EPA finalized the rule revoking
carbofuran tolerances on May 15, 2009 (74 FR 23046 (May 15, 2009)).
    Pursuant to the procedures of the FFDCA, on June 29, 2009
objections to the final revocation rule were filed by the National Corn
Growers Association, National Sunflower Association, National Potato
Council, and FMC Corporation (``Petitioners''). The Petitioners also
requested a hearing on their objections. Coupled with these objections,
FMC filed on the same day yet another series of proposed amendments to
its carbofuran registration. These proposed modifications contained new
application and geographic restrictions as well as an unprecedented
non-governmental scheme for preventing the use of carbofuran in any one
area of the country above a small percentage of that area's
agricultural acreage. The Petitioners relied on these proposed
carbofuran registration amendments as central to, and inextricably
intertwined with, their objection to EPA's prior determination in the
final rule that carbofuran tolerances are unsafe. Specific challenges
raised by the Petitioners involved EPA's decision on the appropriate
level of the additional safety factor to protect infants and children,
EPA's estimate of carbofuran levels in drinking water, EPA's
consideration of the time needed to recover from exposure to
carbofuran, and EPA's refusal to consider a human toxicity study
conducted with carbofuran.
    Today's order denies all of the Petitioners' objections and
requests for hearing. A principal flaw in the Petitioners' objections
is that they have objected to EPA's determination in the final rule on
the safety of carbofuran based on the FIFRA registration amendments
that FMC filed with EPA 45 days after the safety determination was
made. As such, the Petitioners' objections are irrelevant, and thus
immaterial, to the determination EPA made in the final rule. FMC has
the statutory right under FIFRA to request amendment of its carbofuran
registration. What Petitioners may not do is prolong the FFDCA
tolerance revocation process by challenging EPA's safety determination
based on proposed FIFRA registration changes not before EPA at the time
of its final revocation decision.
    It should be noted that EPA's decision on the carbofuran tolerances
is not a determination on FMC's proposed registration amendments. FMC
may continue to pursue these amendments and also the re-establishment
of carbofuran tolerances in light of the amendments. Further, FMC may
seek administrative review, and potentially an administrative hearing,
with regard to any adverse decision issued by EPA on its proposed
amendments. But that process must be played out in the future, a future
in which any decision about the safety of carbofuran is made prior to
the re-introduction of carbofuran residues in food and water, rather
than concurrent with the continued exposure of infants and children to
levels of carbofuran residues that EPA has found to be unsafe.
    Despite the fact that a central aspect of the Petitioners'
objections is based on a flawed conception of the objection process
(i.e., the notion that the objection process presents the opportunity
for a complete reformulation of the matter in dispute, rather than a
chance for a review of the accuracy of EPA's earlier determination),
EPA has undertaken a comprehensive analysis of the merits of each of
the Petitioners' objections and hearing requests. That analysis shows,
as is exhaustively set out in Unit VI, that none of the Petitioners'
requests for hearing meets the regulatory standard for granting a
hearing and none of the Petitioners' objections has merit. There are
numerous reasons for these conclusions, but two related themes running
throughout EPA's analysis are the Petitioners' failure to timely raise
issues or submit supporting documents during the public comment process
on the proposed rule and the Petitioners' failure to object to how EPA,
in the final rule, resolved the issues the Petitioners did raise in the
comment process. EPA considers issues untimely raised to be waived--as
EPA clearly warned at the proposal stage--and finds recycled comments
on the proposed rule to be irrelevant to the detailed determinations
made in the final rule. The rulemaking phase of the revocation process
has a purpose, and parties treat it lightly at their peril. Finally,
EPA notes that an additional problem with the Petitioners' objections
is that once the newly proposed registration amendments are stripped
from the objections, it is not at all clear that any remaining issues,
even if concluded in the Petitioners' favor, would result in lowering
carbofuran's estimated risks--which EPA has estimated as far exceeding
the safety standard--to an acceptable level. For all of these reasons,
the Petitioners' objections and hearing requests are denied.

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

    EPA is taking this action pursuant to the authority in FFDCA
section 408(g)(2)(C), which requires the Agency to issue a final order
resolving the objections to its final rule, issued pursuant to
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), (g)(2)(C).)

III. Statutory and Regulatory Background

    In this Unit, EPA provides background on the relevant statutes and
regulations governing the Petitioners' objections and requests for
hearing as well as on pertinent Agency policies and practices.

A. FFDCA/FIFRA and Applicable Regulations

    1. In general. EPA establishes maximum residue limits, or
``tolerances,'' for pesticide residues in food under section 408 of the
FFDCA (21 U.S.C. 346a). Without such a tolerance or an exemption from
the requirement of a tolerance, a food containing a pesticide residue
is ``adulterated'' under section 402 of the FFDCA and may not be
legally moved in interstate commerce (21 U.S.C. 331,

342). Monitoring and enforcement of pesticide tolerances are carried
out by the U.S. Food and Drug Administration (``FDA'') and the U.S.
Department of Agriculture (``USDA''). Section 408 was substantially
rewritten by the Food Quality Protection Act of 1996 (``FQPA''), which
added the provisions discussed below establishing a detailed safety
standard for pesticides, additional protections for infants and
children, and the process for establishing or revoking tolerances (Pub.
L. 104-170, 110 Stat. 1489 (1996)).
    EPA also regulates pesticides under the Federal Insecticide,
Fungicide, and Rodenticide Act (``FIFRA'') (7 U.S.C. 136 et seq.).
While the FFDCA authorizes the establishment of legal limits for
pesticide residues in food, FIFRA requires the approval of pesticides
prior to their sale and distribution (7 U.S.C. 136a(a)), and
establishes a registration regime for regulating the use of pesticides.
FIFRA regulates pesticide use in conjunction with its registration
scheme by requiring EPA review and approval of pesticide labels and
specifying that use of a pesticide inconsistent with its label is a
violation of federal law (7 U.S.C. 136j(a)(2)(G)). In the FQPA,
Congress integrated action under the two statutes by requiring that the
safety standard under the FFDCA be used as a criterion in FIFRA
registration actions as to pesticide uses that result in dietary risk
from residues in or on food (7 U.S.C. 136(bb)), and directing that EPA
coordinate, to the extent practicable, revocations of tolerances with
pesticide cancellations under FIFRA. (21 U.S.C. 346a(l)(1)).
    2. Safety standard for pesticide tolerances. 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)(ii)). 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.'' This includes
exposure through drinking water and in residential settings, but does
not include occupational exposure. Section 408(b)(2)(D) directs EPA, in
making a safety determination, to:
    Consider, among other relevant factors--* * *
    (vi) Available information concerning the aggregate exposure levels
of consumers (and major identifiable subgroups of consumers) to the
pesticide chemical residue and to other related substances, including
dietary exposure under the tolerance and all other tolerances in effect
for the pesticide chemical residue, and exposure from other non-
occupational sources;

EPA must also consider, in evaluating the safety of tolerances,
``safety factors which * * * are generally recognized as appropriate
for the use of animal experimentation data.'' (21 U.S.C.
346a(b)(2)(D)(ix).)
    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;

    (21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)). This provision also
creates a presumptive additional safety factor for the protection of
infants and children. Specifically, it 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 order as the ``children's safety factor.''
    3. Procedures for establishing, amending, or revoking tolerances.
Tolerances are revoked by rulemaking under the unique procedural
framework set forth in the FFDCA. Section 408(e) of the FFDCA, 21
U.S.C. 346a(e), authorizes EPA to modify or revoke tolerances on its
own initiative.
    In issuing a regulation on its own initiative, EPA must first
publish a notice of proposed rulemaking, and must generally provide at
least 60 days to allow the public to comment on the proposed
regulation. After considering comments submitted during this comment
period, EPA issues a final rule.
    Once EPA issues a final rule, any person may file objections with
EPA and, if desired, request an evidentiary hearing on those objections
(21 U.S.C. 346a(g)(2)). Objections must specify ``with particularity
the provisions of the regulation * * * deemed objectionable and stating
reasonable grounds therefore'' (21 U.S.C. 346a(g)(2)(A); 40 CFR
178.25(a)). Objections and hearing requests must be filed within 60
days (Id.). The statute provides that EPA shall ``hold a public
evidentiary hearing if and to the extent the Administrator determines
that such a public hearing is necessary to receive factual evidence
relevant to material issues of fact raised by the objections'' (21
U.S.C. 346a(g)(2)(B)). EPA regulations make clear that hearings will
only be granted where it is shown that there is ``a genuine and
substantial issue of fact;'' the requestor has identified evidence
``which, if established, will resolve one or more of such issues in
favor of the requestor,'' and the issue is ``determinative'' with
regard to the relief requested (40 CFR 178.32(b)). After consideration
of any objections, EPA must issue a final order stating the action
taken in response to each objection, including a determination as to
whether any hearing is appropriate (21 U.S.C. 346a(g)(2)(C)). The final
order also establishes any revisions to the final regulation EPA deems
to be warranted based on the objections. Id. EPA's final order on the
objections is subject to judicial review in the Court of Appeals,
within 60 days of the publication of the order (21 U.S.C. 346a(h)(1)).
    4. Tolerance reassessment and FIFRA reregistration. EPA revoked the
carbfuran tolerances to implement the Agency's findings made during the
reregistration and tolerance reassessment processes.
    The FQPA required that EPA reassess the safety of all pesticide
tolerances existing at the time of its enactment. (21 U.S.C. 346a(q)).
EPA was given 10 years to reassess the approximately 10,000 tolerances
in existence in 1996. In this reassessment, EPA was required to review
existing pesticide tolerances under the new ``reasonable certainty that
no harm will result'' standard set forth in section 408(b)(2)(A)(i).
(21 U.S.C. 346a(b)(2)(A)(i)). This reassessment was substantially
completed by the August 3, 2006 deadline. Tolerance reassessment was
generally handled in conjunction with a similar program involving
reregistration of pesticides under FIFRA. (7 U.S.C. 136a-1).
Reassessment and reregistration decisions were generally combined in a
document labeled a Reregistration Eligibility Decision (RED).

B. EPA's Human Research Rule

    EPA decisions regarding the use of human studies in pesticide
regulatory decisions are governed by the Protection for Subjects in
Human Research final rule (``Human Research rule''), which
significantly strengthened and expanded protections for subjects of
human research (71 FR 6138 (February 6, 2006)). The framework of the
Human Research rule rests on the basic principle that EPA will not, in
its actions, rely on data derived from unethical research. The rule
divides studies involving intentional dosing of human subjects into two
groups: ``new'' studies--those initiated after April 7, 2006 (the
effective date of the rule)--and ``old'' studies--those initiated
before April 7, 2006. The Human Research Rule forbids EPA from relying
on data from any ``new'' study, unless EPA has adequate information to
determine that the research was conducted in substantial compliance
with the ethical requirements contained therein (40 CFR 26.1705). These
ethical rules are derived primarily from the ``Common Rule,'' (40 CFR
part 26), a rule setting ethical parameters for studies conducted or
supported by the federal government. In addition to requiring informed
consent and protection of the safety of the subjects, among other
things, the rule specifies that ``[r]isks to subjects [must be]
reasonable in relation to * * * the importance of the knowledge that
may reasonably be expected to result [from the study].'' (40 CFR
26.1111(a)(2)). In other words, a study would be judged unethical if it
did not have scientific value outweighing any risks to the test
subjects.
    As to ``old'' studies, the Human Research Rule forbids EPA from
relying on such data if there is clear and convincing evidence that the
conduct of the research was fundamentally unethical or significantly
deficient with respect to the ethical standards prevailing at the time
the research was conducted (40 CFR 26.1704). EPA has indicated that in
evaluating ``the ethical standards prevailing at the time the research
was conducted'' it will consider the Nuremburg Code, various editions
of the Declaration of Helsinki, the Belmont Report, and the Common
Rule, as among the standards that may be applicable to any particular
study (71 FR at 6161). Further, reflecting the concern that
scientifically invalid data are ``always unethical,'' (71 FR at 6160),
the rule limits the human research that can be relied upon by EPA to
``scientifically valid and relevant data'' (40 CFR 26.1701).
    Whether the data are ``new'' or ``old,'' the Human Research rule
forbids EPA from relying on data from any study involving intentional
exposure of pregnant women, fetuses, or children subject to a very
limited exception (40 CFR 26.1703, 1706).
    To aid EPA in making scientific and ethical determinations under
the Human Research rule, the rule established an independent Human
Studies Review Board (HSRB) to review both proposals for new research
(new studies) and reports of completed human research (old studies) on
which EPA proposes to rely (40 CFR 26.1603). The rule directs that the
HSRB shall be comprised of non-EPA employees ``who have expertise in
fields appropriate for the scientific and ethical review of human
research, including research ethics, biostatistics, and human
toxicology'' (40 CFR 26.1603(a)). If EPA decides to rely on the results
from ``old'' research conducted to identify or measure a toxic effect,
EPA must submit the results of its assessment to the HSRB for
evaluation of the ethical and scientific merit of the research (40 CFR
26.1602(b)(2)).
    EPA has established the HSRB as a federal advisory committee under
the Federal Advisory Committee Act (FACA) to take advantage of ``the
benefits of the transparency and opportunities for public
participation'' that accompany a FACA committee (71 FR at 6156). The
HSRB, as appointed by EPA, contains approximately 16 distinguished
experts in the fields of bioethics, biostatistics, human health risk
assessment and human toxicology, primarily from academia (Ref. 10).

IV. 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

    1. In General. 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., 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 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 (i.e., intraspecies variability); and
     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 variability. Further,
as required by FFDCA section 408(b)(2)(C), 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 percent 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.
    2. Acetylcholinesterase Inhibition. 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).
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.
    AChE inhibition is a disruption of the normal process in the body
by which the nervous system chemically communicates with muscles and
glands. Communication between nerve cells and a target cell (i.e.,
another nerve cell, a muscle fiber, or a gland) is facilitated by the
chemical, acetylcholine. When a nerve cell is stimulated it releases
acetylcholine into the synapse (or space) between the nerve cell and
the target cell. The released acetylcholine binds to receptors in the
target cell, stimulating the target cell in turn. As EPA has explained,
``the end result of the stimulation of cholinergic pathway(s) includes,
for example, the contraction of smooth (e.g., in the gastrointestinal
tract) or skeletal muscle, changes in heart rate or glandular secretion
(e.g., sweat glands) or communication between nerve cells in the brain
or in the autonomic ganglia of the peripheral nervous system.'' (Ref.
78 at 10).
    AChE is an enzyme that breaks down acetylcholine and terminates its
stimulating action in the synapse between nerve cells and target cells.
When AChE is inhibited, acetylcholine builds up prolonging the
stimulation of the target cell. This excessive stimulation potentially
results in a broad range of adverse effects on many bodily functions
including muscle cramping or paralysis, excessive glandular secretions,
or effects on learning, memory, or other behavioral parameters.
Depending on the degree of inhibition these effects can be serious,
even fatal.
    EPA's cholinesterase inhibition policy statement explains EPA's
approach to evaluating the risks posed by AChE-inhibiting pesticides
such as carbofuran (Ref. 78 at 10). The policy focuses on three types
of effects associated with AChE-inhibiting pesticides that may be
assessed in animal and human toxicological studies: (1) Physiological
and behavioral/functional effects; (2) AChE inhibition in the central
and peripheral nervous system; and (3) AChE inhibition in red blood
cells and blood plasma. The policy discusses how such data should be
integrated in deriving an acceptable dose (RfD/PAD) for a AChE-
inhibiting pesticide.
    After clinical signs or symptoms, AChE inhibition in the nervous
system provides the next most important endpoint for evaluating AChE-
inhibiting pesticides. Although AChE inhibition in the nervous system
is not itself regarded as a direct adverse effect, it is ``generally
accepted as a key component of the mechanism of toxicity leading to
adverse cholinergic effects'' (Id. at 25). As such, the policy states
that it should be treated as ``direct evidence of potential adverse
effects'' and ``data showing this response provide valuable information
in assessing potential hazards posed by antiAChE pesticides'' (Id.).
Unfortunately, useful data measuring AChE inhibition in the peripheral
nervous system tissues has only been relatively rarely captured by
standard toxicology testing, particularly for the NMC compounds. For
central nervous system effects, however, more recent neurotoxicity
studies ``have sought to characterize the time course of inhibition in
* * * [the] brain, including brain regions, after acute and 90-day
exposures'' (Id. at 27).
    AChE inhibition in the blood is one step further removed from the
direct harmful consequences of AChE-inhibiting pesticides. According to
the policy, inhibition of blood AChEs ``is not an adverse effect, but
may indicate a potential for adverse effects on the nervous system''
(Id. at 28). The policy states that ``[a]s a matter of science policy,
blood AChE data are considered appropriate surrogate measures of
potential effects on peripheral nervous system AChE activity in
animals, for central nervous system (``CNS'') AChE activity in animals
when CNS data are lacking and for both peripheral and central nervous
system AChE in humans'' (Id. at 29). The policy notes that ``there is
often a direct relationship between a greater magnitude of exposure [to
a AChE-inhibiting pesticide] and an increase in incidence and severity
of clinical signs and symptoms as well as blood AChE inhibition'' (Id.
at 30). Thus, the policy regards blood AChE data as ``appropriate
endpoints for derivation of reference doses or concentrations when
considered in a weight-of-the-evidence analysis of the entire database
* * *'' (Id. at 29). Between AChE inhibition measured in red blood cell
(``RBC'') or blood plasma, the policy states a preference for reliance
on RBC AChE measurements because plasma is composed of a mixture of
acetylcholinesterase and butyrylcholinesterase, and inhibition of the
latter is less clearly tied to inhibition of acetylcholinesterase in
the nervous system (Id. at 29, 32).
    EPA has relied on a benchmark dose (BMD) approach for deriving the
PoD from the available rat toxicity studies. A BMD is a point estimate
along a dose-response curve that corresponds to a specific response
level. For example, a BMD10 represents a 10% change from the
background; 10% is often used as a typical value for the response of
concern (Ref. 76). Generically, the direction of change from background
can be an increase or a decrease depending on the biological parameter
and the chemical of interest. In the case of carbofuran, inhibition of
AChE is the toxic effect of concern. Following exposure to carbofuran,
the normal biological activity of the AChE enzyme is decreased (i.e.,
the enzyme is inhibited). Thus, when evaluating BMDs for carbofuran,
the Agency is interested in a decrease in AChE activity compared to
normal activity levels, which are also termed ``background'' levels.
Measurements of ``background'' AChE activity levels are usually
obtained from animals in experimental studies that are not treated with
the pesticide of interest (i.e., ``negative control'' animals).
    In addition to the BMD, a confidence limit was also calculated.
Confidence limits express the uncertainty in a BMD that may be due to
sampling and/or

experimental error. The lower confidence limit on the dose used as the
BMD is termed the BMDL, which the Agency uses as the PoD. Use of the
BMDL for deriving the PoD rewards better experimental design and
procedures that provide more precise estimates of the BMD, resulting in
tighter confidence intervals. Use of the BMDL also helps ensure with
high confidence (e.g., 95% confidence) that the selected percentage of
AChE inhibition is not exceeded. From the PoD, EPA calculates the RfD
and aPAD. Specific to carbofuran and the other NMCs, EPA the FIFRA SAP
has reviewed and supported the statistical methods used to derive the
BMD and BMDLs on multiple occasions (Refs. 34, 35, 36).
    In the Agency's BMD analysis for carbofuran, EPA used a response
level of 10% brain AChE inhibition; this value represents the estimated
dose where AChE is inhibited by 10%, compared to untreated animals. For
the last several years EPA has used the 10% value to regulate AChE
inhibiting pesticides, including organophosphorous pesticides (OPs) and
NMCs. For a variety of toxicological and statistical reasons, EPA chose
10% brain AChE inhibition as the response level for use in BMD
calculations. EPA analyses have demonstrated that 10% is a level that
can be reliably measured in the majority of rat toxicity studies; is
generally at or near the limit of sensitivity for discerning a
statistically significant decrease in AChE activity across the brain
compartment; and is a response level close to the background (Refs. 34,
35).

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 probabalistic
\1\ 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.
---------------------------------------------------------------------------

    \1\ 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. 77). 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.
---------------------------------------------------------------------------

    1. Exposure from Food. The level of human exposure to pesticide
residues in food is a function of both the pesticide residues in food
and the amount of food consumed. 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
Pesticide Data Program (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 VI.E.1).
    EPA relies on USDA's Continuing Survey of Food Intake by
Individuals (CSFII) for information on food consumption by the US
population as well as 32 subgroups based on age, gender, ethnicity, and
region. The latest CSFII was conducted 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 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, etc.). 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 computer program to estimate exposure and risk.
    The DEEM-FCID computer program estimates exposure by combining data
on human consumption amounts with residue values in food commodities.
DEEM-FCID also compares exposure estimates to appropriate RfD or PAD
values to estimate risk. EPA uses DEEM-FCID to estimate exposure for
the general U.S. population as well as for 32 subgroups based on age,
sex, ethnicity, and region. DEEM-FCID 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.
    For carbofuran's assessment, EPA used DEEM-FCID to calculate risk
estimates based on a probabilistic distribution. DEEM-FCID 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 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 exposure 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 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 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; and

    (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)). 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 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 percent cropped area factors and the Index Reservoir
scenario was reviewed and approved by the FIFRA SAP in 1999 and 1998,
respectively (Refs. 30, 31).
    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's models take into account that pesticide
residues in water fluctuate daily, seasonally, and yearly as a result
of the timing of pesticide applications, 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 uses the output of daily concentration values from tier two
modeling as an input to DEEM-FCID, 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 exposures to pesticide residues are therefore not
expected to vary substantially throughout the country, drinking water
is locally derived and consumed and there can be significant variations
in pesticide levels in local watersheds due to geographic, climatic,
and other factors. To be protective of all population subgroups, EPA
uses modeled estimates from vulnerable watersheds in calculating
aggregate exposure.
    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 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 one 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 suggested by the FIFRA SAP in the
context of assessing AChE inhibition from cumulative exposures to OP
pesticides (Ref. 33).

C. Selection of Acute Dietary Exposure Level of Concern

    Because probabilistic assessments generally are based on 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 1000 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. 77).

V. Carbofuran Background and Regulatory History

A. Tolerance Reassessment and Pesticide Reregistration

    In July 2006, EPA completed a refined acute probabilistic dietary
risk assessment for carbofuran as part of the tolerance reassessment
program under section 408(q) of the FFDCA and pesticide reregistration
under section 4 of FIFRA. The assessment was conducted using Dietary
Exposure Evaluation Model-Food Commodity Intake Database (DEEM-
FCIDTM, Version 200-2.02), 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 \2\ (PDP), estimated percent crop treated
information, and processing/cooking factors, where applicable. The
assessment was conducted applying an additional 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 significantly above EPA's level of concern
(Ref. 14). Based in part on the results of that assessment, EPA
concluded that carbofuran failed to meet the revised safety standard in
FFDCA section 408(b) and the standard for FIFRA reregistration.\3\
---------------------------------------------------------------------------

    \2\ USDA's Pesticide Data Program monitors for pesticides in
certain foods at the distribution points just before release to
supermarkets and grocery stores.
    \3\ Although not relevant to this proceeding, in addition to
determining that use of carbofuran resulted in unacceptable dietary
risks, EPA concluded that use of carbofuran did not meet the
standard for FIFRA registration based on unacceptable occupational
and ecological risks.
---------------------------------------------------------------------------

    The tolerance reassessment and FIFRA reregistration process for
carbofuran contained numerous opportunities for public participation.
These included public comment periods on the preliminary ecological
risk assessment (June-August 2005), the preliminary human health risk
assessment (September-November 2005), the revised combined risk
assessment (March-May 2006), and the interim Registration Eligibility
Document (RED) (August-November 2006). EPA received over 200 comments
(plus a letter campaign supporting carbofuran with 2,896 signatories)
to the 2006 RED. FMC submitted extensive comments throughout the
process (including, but not limited to, a comment of 62 pages plus 13
attachments totaling over 900 pages on August 23, 2005, a letter with
20 attachments on November 11, 2005, 46 pages of comments on January
26, 2006, 78 pages of comments on February 17, 2006, a 15-page letter
with 8 attachments on May 22, 2006, over 200 pages on May 24, 2006, and
other submissions. Following issuance of the RED in August 2006, FMC
stated that they would be submitting new data to refute EPA's
ecological and human health risk concerns, as well as EPA's benefits
assessments. Twenty-three submissions with studies and analyses were
submitted in 2007, all of which EPA reviewed. FMC submitted 175 pages
of comments to the proposed tolerance revocations jointly with the NPC,
NCGA, NCC, and NSA on 9/29/09. The Agency has also met numerous times
with FMC, growers, and other stakeholders regarding carbofuran.
    One particular aspect of the risk assessment process that involved
substantial public participation opportunities was EPA's review of the
human toxicology studies performed with carbofuran. In making a
determination on whether these studies met the standards of the Human
Research rule, EPA, as required, sought the advice of the HSRB. The
HSRB review process includes the opportunity for the public both to
submit written comments and to make an oral presentation to the HSRB.
FMC gave both written and oral comments at the HSRB meeting, which was
held May 2-4, 2006. FMC also submitted written comments on the final
HSRB report on the meeting.

B. Draft Notice of Intent to Cancel Carbofuran Registrations

    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.\4\ As part of
that process, EPA presented its dietary risk assessment of carbofuran
to the FIFRA SAP, and requested comment on key issues in the risk
assessment: The Agency's approach to selecting the point of departure
and the children's safety factor. FMC and the remaining Petitioners
participated in this meeting, making substantial presentations to the
SAP. As described in the proposal, the Agency believes that the Panel's
responses unambiguously support the Agency's approach with regard to
carbofuran's hazard identification and hazard characterization (73 FR
44875 (July 31, 2008)). In addition, EPA believes that, on balance, the
application of a 4X children's safety factor is consistent with the
SAP's advice. Additional detail on the SAP's advice and EPA's responses
can be found at Ref. 83.
---------------------------------------------------------------------------

    \4\ The draft NOIC was based on all of carbofuran's combined
risks--dietary, occupational, and ecological. Because some non-food
use registrations remain, EPA anticipates issuing the NOIC
subsequent to undertaking the activities required to revoke the
carbofuran tolerances to cancel these remaining uses.
---------------------------------------------------------------------------

C. Proposed Revocation of Carbofuran Tolerances

    Having considered the comments from the SAP, EPA initiated the
process to revoke all carbofuran tolerances, publishing a proposed
revocation on July 31, 2008 (73 FR 44,864 (July 31, 2008) (FRL-8378-
8)). EPA proposed to revoke all of the existing tolerances for residues
of carbofuran on the grounds that aggregate exposure from all uses of
carbofuran fails to meet the FFDCA section 408 safety standard (Id).
Based on the contribution from food alone, EPA calculated dietary
exposures to carbofuran exceed EPA's level of concern for all of the
more sensitive subpopulations of infants and children. At the 99.9th
percentile, aggregate carbofuran dietary exposure from food and
drinking water from contaminated ground water was estimated to range
from 1100% of the aPAD for adults, to greater than 10,000% of the aPAD
for infants, the population subgroup with the highest estimated dietary
exposure (Ref. 12). Similarly, aggregate dietary exposures from food
and drinking water from surface water, based on contamination from use
on corn in Nebraska, ranged from 340% of the aPAD for adults, to 3,900%
aPAD for infants. EPA also determined that, based on actual residue
levels measured in food in commerce, individual children consuming
typical amounts of a single food item received unsafe levels of
carbofuran. For example, based on the level of residues detected on in
the food supply, a child between 3-5 years, who consumed \1/2\ cup of
cantaloupe, would receive a dose ranging between 180% and 7,200% of the
aPAD. Finally, the proposal discussed a number of sensitivity analyses
the Agency had calculated 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.
    EPA held a 60-day comment period on the proposed revocation rule.
In the proposed rule, EPA made clear that if any person had concerns
with EPA's proposed revocation, those concerns must be raised during
the comment period to be preserved. Specifically, EPA stated:

    In addition to submitting comments in response to this proposal,
you may also submit an objection at the time of the final rule. If
you anticipate that you may wish to file objections to the final
rule, you must raise those issues in your comments on this proposal.
EPA will treat as waived, any issue not originally raised in
comments on this proposal. Similarly, if you fail to file an
objection to the final rule within the time period specified, you
will have waived the right to raise any issues resolved in the final
rule. After the specified time, issues resolved in the final rule
cannot be raised again in any subsequent proceedings on this rule.

(73 FR at 44865).

D. Petitioners' Comments on the Proposed Rule

    The comment period for the proposed rule closed on September 29,
2008. During the comment period, the Petitioners submitted comments
challenging particular aspects of EPA's risk assessment. For example,
the Petitioners challenged the basis for EPA's 4X children's safety
factor, and the method and assumptions on which EPA relied to estimate
drinking water concentrations. In addition, the registrant, FMC
Corporation, requested that EPA cancel the use on 22 of the crops on
which it was registered, including many of the foods posing the highest
risks to children. FMC also requested that EPA modify its labels to
include a number of additional restrictions intended to mitigate the
risks identified in EPA's risk assessment. For example, use was
prohibited on much of the Eastern US to protect vulnerable sources of
groundwater; use restrictions were imposed in other areas of the
country, preventing use within set distances to prevent runoff into
sources of surface water drinking water supplies.
    On November 7, 2008, the Petitioners submitted additional
information as a supplement to their September comments. Specifically,
they submitted carbofuran use data that the Petitioners used in
preparing its surface water assessments. The information consisted of a
spreadsheet that contained all of the data provided to the Water Panel
by FMC, and a document that explained the materials, methods, and
procedures employed by the Panel to utilize this data.
    On December 24, 2008, FMC submitted a petition requesting that EPA
stay the effective date of the tolerance revocations, and that EPA
consider additional information, including further risk mitigation
measure that the registrant intended to implement, as well as
additional analyses that the Petitioners' experts were developing.

E. Final Rule Revoking Carbofuran Tolerances

    On May 15, 2009, EPA published its final rule, based on a revised
risk assessment that addressed the voluntary cancellations and label
restrictions submitted by the close of the September 29 comment period.
The only food uses that remained registered after the voluntary
cancellations were sunflowers, corn, potatoes, and pumpkins. In
response to the changes made on the labels, EPA revised its risk
assessment to account for the reduced number of crops, the altered
geographic restrictions, and the additional risk mitigation measures
proposed as part of FMC's comments.
    Having considered all comments received by the close of the comment
period, and based on its revised analyses, EPA concluded that aggregate
exposures from all remaining uses of carbofuran were still unsafe for
infants and children, and that revocation of the remaining tolerances
was warranted. The final rule explained that, although the recent
cancellation of several registered uses reduced the dietary risks to
children, EPA's analyses still showed that estimated exposures
significantly exceed EPA's level of concern for children. For example,
EPA determined that the estimated risks could be as high as 9,400% of
the aPAD for infants. A detailed description of the risk assessment
supporting the final rule follows.

    1. Toxicity. AChE inhibition in brain and the PNS is the initial
adverse biological event which results from exposure to carbofuran, and
with sufficient levels of inhibition leads to other effects such as
tremors, dizziness, as well as gastrointestinal and cardiovascular
effects, including bradycardia (Ref. 15). Thus, AChE inhibition
provides the most appropriate effect to use in risk extrapolation for
derivation of RfDs and PADs. Protecting against AChE inhibition ensures
that the other adverse effects associated with cholinergic toxicity,
mentioned above, do not occur.
    There are three studies available that compare the effects of
carbofuran on eleven-day-old rats (i.e., post-natal day 11 or PND11)
rats with those in young adult rats (herein called comparative AChE
studies) (Refs. 1, 2, 4, and 66). Two of these studies were submitted
by FMC, the registrant, and one was performed by EPA-ORD. An additional
study conducted by EPA-ORD involved PND17 rats (Ref. 63). 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.
PND17 rats are believed to be closer developmentally to human toddlers
(Refs. 10, 22, and 23). Other studies in adult rats used in the
Agency's analysis included additional data from EPA-ORD (Refs. 54, 62,
and 66).
    The studies in juvenile rats show a consistent pattern that
juvenile rats are more sensitive than adult rats to the effects of
carbofuran. These effects include inhibition in AChE in addition to
incidence of clinical signs of neurotoxicity such as tremors. This
pattern has also been observed for other NMC pesticides, which exhibit
the same mechanism of toxicity as carbofuran (Ref. 81). It is not
unusual for juvenile rats, or indeed, for infants or young children, to
be more sensitive to chemical exposures as metabolic detoxification
processes in the young are still developing. Because juvenile rats,
called `pups' herein, are more sensitive than adult rats, data from
pups provide the most relevant information for evaluating risk to
infants and young children and are thus used to derive the PoD. In
addition, typically (and this is the case for carbofuran) young
children (ages 0-5 years) tend to be the age groups most exposed to
carbofuran because they tend to ingest larger amounts of food and water
per their body weight than do teenagers or adults. As such, the focus
of EPA's analysis of carbofuran's dietary risk from residues in food
and water is on young children (ages 0 to 5 years). Since these age
groups experience the highest levels of dietary risk, protecting these
groups against the effects of carbofuran will, in turn, also protect
other age groups.
    The Agency used a meta-analysis to calculate the BMD10
and BMDL10 for pups and adults; this analysis includes brain
data from studies where either adult or juvenile rats or both were
exposed to a single oral dose of carbofuran. The Agency used a dose-
time-response exponential model where benchmark dose and half-life to
recovery can be estimated together. This model and the statistical
approach to deriving the BMD10 s, BMDL10 s, and
half-life to recovery have been reviewed and supported by the FIFRA SAP
(Refs. 34, 35, and 36). The meta-analysis approach offers the advantage
over using single studies by combining information across multiple
studies and thus provides a robust PoD.
    For AChE-inhibiting pesticides, EPA generally evaluates the effects
of the pesticide on both brain and RBC AChE. RBC AChE is used as a
surrogate for effects on the PNS because data directly measuring
effects on the PNS are difficult to obtain.
    Using quality brain AChE data from the three studies (two FMC, one
EPA-ORD) conducted with PND11 rats, in combination, provides data to
describe both low and high doses. By combining the three studies in
PND11 animals together in a meta-analysis, the entire dose-response
range is covered. The results of the BMD analysis for PND11 pup brain
AChE data provide a BMD10 of 0.04 mg/kg/day and
BMDL10 of 0.03 mg/kg/day--this BMDL10 of 0.03 mg/
kg/day provides the PoD (Ref. 70).
    EPA, however, lacked adequate data on carbofuran's effects on RBC
AChE. Two studies required from FMC were rejected as flawed. To account
for the lack of data in the PNS and/or a surrogate (i.e., RBC AChE
inhibition data) in pups at the low end of the response curve, and for
the fact that RBC AChE inhibition appears to be a more sensitive point
of departure compared to brain AChE inhibition, EPA determined that,
consistent with the statutory mandate, some portion of the statutory
default 10X children's safety factor needed to be retained. Because
there are some carbofuran data that characterize the toxicity in
juveniles, EPA concluded that the weight-of-the-evidence supports
reducing the statutory factor of 10X to a value lower than 10X. This
results in a children's safety factor that is less than 10 but more
than 1.
    The modified children's safety factor takes into account the
greater sensitivity of the RBC AChE. The preferred approach to
comparing the relative sensitivity of brain and RBC AChE inhibition
would be to compare the BMD10 estimates. However,
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. As an alternative approach, EPA used the ratio of brain
to RBC AChE inhibition at the BMD50, since there are quality
data at or near the 50% response level such that a reliable estimate
can be calculated. EPA estimated the RBC BMD50 to brain
BMD50 potency ratio using EPA's data for RBC (the only
reliable RBC data in PND11 animals for carbofuran) and all available
data in PND11 animals for brain. There is, however, an assumption
associated with using the 50% response level--namely that the magnitude
of difference between RBC and brain AChE inhibition is constant across
dose. In other words, EPA is assuming the RBC and brain AChE dose
response curves are parallel. There are currently no data to test this
assumption for carbofuran.
    Comparing RBC BMD50 and brain BMD50 AChE
inhibition, EPA calculated a BMD50 ratio of 4.1X.
Accordingly, EPA concluded that a children's safety factor of 4X would
be protective of infants and children.
    Using the BMDL10 of 0.03 mg/kg/day, combined with the
default 10X interspecies and intraspecies factors, along with the 4X
children's safety factor results in an aPAD = 0.000075 mg/kg/day for
infants and children. The aPAD for youths and adults is calculated in
the same manner, but EPA does not apply the 4X children's safety
factor, resulting in an aPAD of 0.0002 mg/kg/day.
    2. Acute Exposures from Food. The estimated acute dietary exposure
from carbofuran residues in food alone (i.e., assuming no additional
carbofuran exposure from drinking water), is below EPA's level of
concern for the U.S. Population and all population subgroups. Children
1 to 2 years of age (78% aPAD) were the most highly exposed population
subgroup when food only was included. The major driver of the acute
dietary exposure risk (food only) for Children 1 to 2 years is milk, at
greater than 90% of the exposure.
    3. Acute Exposures from Drinking Water. EPA's analyses show that
those individuals-both adults as well as children--who receive their
drinking water from vulnerable sources are exposed to 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. It could also include 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 is more
uncertainty associated with these exposure estimates.
    a. Ground Water. In EPA's revised assessment, ground water
concentrations were estimated for all remaining crops on carbofuran
labels, and used two new Tier 2 scenarios. Based on a new corn
scenario, representative of potentially vulnerable areas in the upper
Midwest, EPA estimated 1-in-10-year concentrations for ground water
source drinking water of 16 to 1.6 x 10-3 [mu]g/L, for pH
6.5 and 7, respectively. A potato scenario representing use in the
Northwest estimated no measurable concentrations of carbofuran in
ground water. Other remaining uses were modeled using a Tier 1 ground
water model (Screening Concentration in Groundwater) with estimated
peak 90-day concentrations of 48-178 [mu]g/L, depending on application
rate. Well setback prohibitions of 50 feet were proposed on the
September 2008 label for the flowable and granular formulations in
select counties in Kentucky (seven counties), Louisiana (one county),
Minnesota (one county), and Tennessee (one county). Analysis of the
impact of these setbacks for the use on corn indicated that the
setbacks would not reduce concentrations significantly at locations
where exposure to carbofuran in ground water is of concern because at
acid pHs, carbofuran does not degrade sufficiently during the travel
time from the application site to the well to substantially reduce the
concentration.
    Exposure estimates for this assessment are drawn primarily from
EPA's modeling. To conduct its modeling, EPA examined readily available
data with respect to ground water and soil pH to evaluate the spatial
variability of pH. Ground water pH values can span a wide range; this
is especially true for shallow ground water systems, where local
conditions can greatly affect the quality and characteristics of the
water (higher or lower pHs compared to average values). The ground
water simulations reflect variability in pH by modeling carbofuran
leaching in four different pH conditions (pH 5.25, 6.5, 7.0, and 8.7),
representing the range in the Wisconsin aquifer system. The upper and
lower bound of pH values that EPA chose for this assessment were
measured values from the aquifer, and the remaining two values were
chosen to reflect common pH values between the measured values. Based
on EPA's assessment, the maximum 1-in-10-year peak carbofuran
concentrations in vulnerable ground water for a single application on
corn in Wisconsin, at a rate of 1 pound per acre were estimated to
range from a low of less than 1 ppb based on a pH of 7 or higher, to a
high of 16 ppb, based on a pH of 6.5.
    The results of EPA's revised corn modeling, based on a scenario in
Wisconsin, are consistent with the results of the PGW study developed
by FMC in Maryland in the early 1980s. Using higher use rates than
currently permitted, the peak concentration measured in the PGW study
was 65 ppb; when scaled to current use rates, the estimated peak
concentration was 11 ppb. EPA's modeling is also consistent with a
number of other targeted ground water studies conducted in the 1980s
showing that high concentrations of carbofuran can occur in vulnerable
areas; the results of these studies as well as the PGW study are
summarized in References 13 and 67.
    While there have been additional ground water monitoring studies
that included carbofuran as an analyte since that time, there has been
no additional monitoring targeted to carbofuran use in areas where
aquifers are vulnerable. However, data compiled in 2002 by EPA's Office
of Water show that carbofuran was detected in treated drinking water at
a few locations. Based on samples collected from 12,531 ground water
supplies in 16 states, carbofuran was found at one public ground water
system at a concentration of greater than 7 ppb and in two ground water
systems at concentrations greater than 4 ppb (measurements below this
limit were not reported). An infant receiving these concentrations
would receive doses equivalent to 220% of the aPAD or 130% aPAD,
respectively, based on a single 8 ounce serving of water. As this
monitoring was not targeted to carbofuran, the likelihood is low that
these samples capture peak concentrations. Given the lack of targeted
monitoring, EPA has primarily relied on modeling to develop estimates
of carbofuran residues in ground water sources of drinking water.
    EPA compiled a distribution of estimated carbofuran concentrations
in water based on these estimates, which was used to generate
probabilistic assessments of the potential exposures from drinking
water derived from vulnerable ground water sources. Based on these
assessments, estimated exposures ranged between 770% aPAD for adults to
9400% aPAD for infants.
    b. Surface Water. For the final rule, EPA conducted additional
refined modeling based on the September 2008 label submitted by FMC.
The modeling addressed all of the domestic uses that remain registered,
and included certain refinements to better understand the impacts of
varying pH. EPA also conducted modeling to assess the impact of the
proposed spray drift buffer requirements and other spray drift measures
included on the September label.
    EPA estimated carbofuran concentrations resulting from the use on
pumpkins by adjusting the estimated drinking water concentrations
(EDWC) from a previous run simulating melons in Missouri; adjustments
accounted for differences in application rate and row spacing. Two
EDWCs were calculated for pumpkins: One based on a 36-inch row spacing,
representing pumpkins for consumption (77.6 ppb); and a second based on
a 60-inch row spacing, representing decorative pumpkins (46.6 ppb).
    EPA had previously evaluated the corn rootworm rescue treatment at
seven representative sites, representing use in states with extensive
carbofuran usage at locations more vulnerable than most in each state
in areas corn is grown. Using measured rainfall values, and assuming
typical rather than maximum use rates, peak concentrations for the corn
rescue treatments simulated for Illinois, Iowa, Indiana, Kansas,
Minnesota, Nebraska, and Texas ranged from 16.6-36.7 ppb (Ref. 47).
Under the revised assessment to account for the September 2008 use
restrictions, concentrations for corn, calculated including the
proposed spray drift buffers in Kansas and Texas, decreased 5.1% and
4.7%, respectively, from simulations with no buffer from the previous
assessment (Ref. 47). In Kansas, the 1-in-10-year peak EDWCs decreased
from 33.5 to 31.8 ppb when a 300-foot buffer was added, and in Texas,
from 29.9 to 28.5 ppb with the addition of a 66-foot buffer.
    For the sunflower use, 12 simulations were performed for
sunflowers, 9 in Kansas, and 3 in North Dakota. The North Dakota
scenario was used to represent locations where sunflowers are grown
that are vulnerable to pesticide movement to surface water while the
Kansas scenario represents places that are not particularly vulnerable,
based on the limited rainfall and generally well-drained soils
(hydrologic group B soils) that are found in that area. Estimated 1-in-
10-year concentrations ranged from 11.6 to 32.7

[mu]g/L. When simulating three applications, one at plant and two
foliar with a 14-day interval between the two foliar applications and a
66-foot buffer, the 1-in-10-year peak EDWC for North Dakota was 22.4
[mu]g/L. In contrast, the same three applications in Kansas with a 14-
day interval between the foliar applications and a 300-foot buffer
produced a 1-in-10-year peak EDWC of 20.5 [mu]g/L. The 1-in-10-year
peak EDWCs, assuming that carbofuran is applied only at plant, were
14.0 and 16.0 [mu]g/L in Kansas and North Dakota respectively. EPA also
evaluated the impact of pH on carbofuran concentrations for sunflowers,
resulting in a 10% decrease in 1-in-10-year peak concentrations
assuming high pH in the reservoir. Spray drift buffers of 66 and 300
feet decreased concentrations 4.7 and 5.1% for corn and 10.0% and 16.0%
for sunflowers, respectively, in comparison to previous labels that had
no spray drift buffer requirements. Additional details on these
assessments can be found at Reference 84.
    These predicted carbofuran water concentrations are similar or
lower than the peak concentrations reported in the United States
Geological Survey-National Ambient Water Quality Survey (USGS-NAWQA)
monitoring data. In addition, these data, which represent
concentrations in surface water prior to any treatment by a public
drinking water system, are consistent with the results of the 2002 data
on finished water compiled by EPA's Office of Water. Based on samples
collected from 1,394 surface water source drinking water supplies in 16
states, carbofuran was found at no public drinking water supply systems
at concentrations exceeding maximum contaminant level (MCL) of 40 ppb.
However, carbofuran was found at one surface water public water system
in finished (i.e., post-treatment) water at concentrations greater than
4 ppb (measurements below this limit were not reported). Sampling is
costly and is conducted typically four times a year or less at any
single drinking water facility. The overall likelihood of collecting
samples that capture peak exposure events is, therefore, low. For
chemicals with acute risks of concern, such as carbofuran, higher
concentrations and resulting risk is primarily associated with these
peak events, which are not likely to be captured in monitoring unless
the sampling rate is very high.
    There are few surface water field-scale studies targeted to
carbofuran use that could be compared with modeling results. Most of
these studies were conducted in fields that contain tile drains, which
is a common practice throughout midwestern states to increase drainage
in agricultural fields (Ref. 13). Drains are common in the upper
Mississippi river basin (Illinois, Iowa, and the southern part of
Minnesota), and the northern part of the Ohio River Basin (Indiana,
Ohio, and Michigan) (Ref. 58). Although it is not possible to directly
correlate the concentrations found in most of the studies with drinking
water concentrations, these studies confirm that carbofuran use under
such circumstances can contaminate surface water, as tile drains have
been identified as a conduit to transport water and contaminants from
the field to surface waters.
    EPA conducted dietary exposure analyses based on the modeling
scenarios for the proposed September 2008 label. Exposures from all
modeled scenarios substantially exceeded EPA's level of concern (Ref.
12). For example, a Kansas sunflower scenario, assuming two foliar
applications at a typical 1 lb active ingredient (a.i.) per acre use
rate, applied at 14-day intervals, estimated a 1-in-10-year peak
carbofuran water concentration of 11.6 ppb. Exposures at the 99.9th
percentile based on this modeled distribution ranged from 160% of the
aPAD for youths 13 to 19 years, to greater than 2,000% of the aPAD for
infants. This scenario is intended to be representative of sites that
are less vulnerable than most on which sunflowers could be grown. By
contrast, exposure estimates from a comparable North Dakota sunflower
scenario, intended to represent more vulnerable sites, estimated a 1-
in-10-year peak concentration of 22.4 ppb. These concentrations would
result in estimated exposures ranging between 450% aPAD for youths 13
to 19 years, to 5,500% aPAD for infants. Similarly, exposures based on
a Washington surface water potato scenario, and using a 3 lb a.i. acre
rate, ranged from 230% of the aPAD for children 6 to 12 years to 890%
of the aPAD for infants, with a 1-in-10-year peak carbofuran
concentration of 7.2 ppb. Although other crop scenarios resulted in
higher exposures, estimates for these two crops are presented here, as
they are major crops on which a large percentage of carbofuran use
occurs. For example, one of EPA's refined exposure analyses is based on
a Nebraska corn rootworm ``rescue treatment'' scenario, and assumes a
single aerial application at a typical rate of 1 lb a.i. per acre. The
full distribution of daily concentrations over a 30-year period was
used in the probabilistic dietary risk assessment. The 1-in-10-year
peak concentration of the distribution of values for the Nebraska corn
rescue treatment was 22.3 ppb. Estimated dietary exposures based on
these concentrations ratned from 340% of the aPAD for adults to 3900%
of the aPAD for infants. More details on these assessments, as well as
the assessments EPA conducted for other crop scenarios, can be found in
References 12, 47, and 67.
    4. Aggregate (food and water) Exposures. EPA conducted a number of
probabilistic analyses to combine the national food exposures with the
exposures from the individual region and crop-specific drinking water
scenarios. Although food is distributed nationally, and residue values
are therefore not expected to vary substantially throughout the
country, drinking water is locally derived and consumed and
concentrations of pesticides in source water fluctuate over time and
location for a variety of reasons. Consequently, EPA conducted several
estimates of aggregate dietary risks by combining exposures from food
and drinking water. These estimates showed that, because drinking water
exposures from any of the crops on the label exceed safe levels,
aggregate exposures from food and water are unsafe. Although EPA's
assessments showed that, based on the Idaho potato scenarios, exposures
from ground water from use on potatoes would be safe, surface water
exposures from carbofuran use on potatoes far exceed the safety
standard. More details on the individual aggregate assessments
presented below, as well as the assessments EPA conducted for other
regional and crop scenarios, can be found in References 12 and 13.
    The results of aggregate exposures from food and from drinking
water derived from ground water in extremely vulnerable areas (i.e.,
from shallow wells associated with sandy soils and acidic aquifers,
such as are found in Wisconsin), ranged from 780% of the aPAD for
adults, to 9,400% of the aPAD for infants.
    The results of aggregate exposure from food and water derived from
one of the least conservative surface water scenarios--Kansas
sunflower, with two foliar applications--ranged from 190% of the aPAD
for adults to 2,100% aPAD for infants. These estimates reflect the
risks only for those people in watersheds with characteristics similar
to that used in the scenario, and assuming that water treatment does
not remove carbofuran. The estimated water concentrations are
comparable to the maximum peak concentrations reported in monitoring
studies that were not designed to detect peak, daily

concentrations of carbofuran in vulnerable locations.
    More details on this assessment, as well as the assessments EPA
conducted for other crop scenarios, can be found in References 12, 47,
and 67. For example, in the proposed rule, EPA presented the results
from aggregate exposures resulting from a Nebraska surface water
scenario based on a Nebraska corn rootworm ``rescue treatment.''
Estimated exposures from that scenario ranged from 330% of the aPAD for
youths 13 to 19 years to 3,900% of the aPAD for infants.
    As noted previously, EPA's food and water exposure assessments
typically sum exposures over a 24-hour period, and EPA used this 24-
hour total in developing its acute dietary risk assessment for
carbofuran. Because of the rapid nature of carbofuran toxicity and
recovery, EPA conducted an analysis using information about dietary
exposure, timing of exposure within a day, and half-life of AChE
inhibition from rats to estimate risk to carbofuran at durations less
than 24 hours. Specifically, EPA has evaluated individual eating and
drinking occasions and used the AChE half-life to recovery information
(herein called half-life information) to estimate the residual effects
from carbofuran from previous exposures within the day. The carbofuran
analyses are described in the 2009 aggregate (dietary) memo (Ref. 55).
    Using the two FMC time course studies in rat pups, EPA calculated
half-lives for recovery of 186 and 426 minutes (Refs. 24 and 25). The
two values provide an indication that half-lives to recovery can vary
among juvenile rats. By extension, children are expected to vary in
their ability to recover from AChE inhibition where longer recoveries
would be associated with a potentially higher ``persisting dose'' (as
described below).
    This analysis had little impact on the exposures from food alone.
However, accounting for drinking water consumption throughout the day
and using the half-life to recovery information, risk is reduced by
approximately 2-3X. Consequently, risk estimates for which food and
drinking water are jointly considered and incorporated (i.e., Food +
Drinking Water) are also reduced considerably--by a factor of two or
more in some cases--compared to baseline. But even though the risk
estimates from aggregate exposure are reduced, they nonetheless still
substantially exceed EPA's level of concern for infants and children.
Using drinking water derived from the surface water from the Idaho
potato surface water scenario, which estimated one of the lowest
exposure distributions, aggregate exposures at the 99.9th percentile
ranged from 328% of the aPAD under the scenario for which infants
rapidly metabolize carbofuran (e.g., 186 minute half-life), to a high
of 473% of the aPAD under the scenario for which infants metabolize
carbofuran more slowly, (e.g., scenarios in which a 426 minute half
life is assumed).
    Moreover, even accounting for the estimated decreased risk from
accounting for carbofuran's rapid reversibility, the Agency remains
concerned about the risks from single eating or drinking events, as
illustrated in the following example, based on an actual food
consumption diary from the CSFII survey. A 4-month old male non-nursing
infant weighing 10 kg is reported to have consumed a total of 1,070
milliters (ml) of indirect water over eight different occasions during
the day. The first eating occasion occurred at 6:30 a.m., when this 4
month old consumed 8 fluid ounces of formula prepared from powder. The
FCID food recipes indicate that this particular food item consists of
approximately 87.7% water, and therefore, 8 ounces of formula contains
approximately 214 ml (or grams) of indirect water; with the powder
(various nutrients, dairy, soy, oils, etc.) accounting for the
remaining 12.3%. This infant also reportedly consumed a full 8-ounce
bottle of formula at 12 p.m., 4 p.m., and 8 p.m. that day. The food
diary also indicates that the infant consumed about 1 tablespoon of
water (14.8 ml) added to prepare rice cereal at 10 a.m., about 2 ounces
of water (59.3 ml) added to pear juice at 11 a.m., another \1/2\ tsp of
water (2.5 ml) to prepare more rice cereal at 8:30 p.m.; and finally,
he consumed another 4 ounces of formula (107 ml) at 9:30 p.m.
    The infant's total daily water intake (1,070 ml, or approximately
107 ml/kg/day) is not overly conservative, and represents substantially
less than the 90th percentile value from CSFII on a ml water/kg
bodyweight (ml/kg/bw) basis. As noted, carbofuran has been detected in
finished water at concentrations of 4 ppb. For this 10 kg body weight
infant, an 8-ounce bottle of formula prepared from water containing
carbofuran at 4 ppb leads to drinking water exposures of 0.0856
micrograms of active ingredient/kilogram of bodyweight ([micro]g ai/kg
bw), or 114% of the aPAD. Based on the total daily water intake of
1,070 ml/day (no reversibility), total daily exposures from water at 4
ppb concentration would amount to 0.4158 [micro]g ai/kg bw, or 555% of
the aPAD; this is the amount that would be used for this person-day in
the Total Daily Approach.
    Peak inhibition occurs following each occasion on which the infant
consumed 8 fluid ounces of formula (6 a.m., 12 p.m., 4 p.m. and 8
p.m.); however, the maximum persisting dose occurs following the 9:30
p.m. eating occasion, based on a 186-minute half-life parameter. This
produces a maximum persisting dose of 0.1457 [micro]g ai/kg bw, or
about 30% of the total daily exposure of 0.4158 [micro]g ai/kg bw
derived above, or expressed as a fraction of the level of concern, the
maximum persisting dose amounts to about 194% of the aPAD (or 30% of
554%). Note that with drinking water concentration at 4 ppb, an infant
consuming one 8 oz bottle of formula--prepared from powder and tap
water containing carbofuran at 4 ppb will obtain exposures of
approximately 114% of aPAD. Since many infants consume the equivalent
of this amount on a single eating occasion, accounting for
reversibility over multiple occasions is not essential to ascertain
that infants quite likely have obtained drinking water exposures to
carbofuran exceeding the level of concern based on drinking water
concentrations found in public drinking water supplies.
    In this regard, it is important to note EPA's Eating Occasion
Analyses underestimate exposures to the extent that they do not take
into account carry-over effects from previous days, and because
drinking water pesticide concentrations are randomly picked from the
entire 30-year distribution. As discussed previously, DEEM-FCID
[FN(TM)] is a single day dietary exposure model, and the DEEM-based
Eating Occasion Analysis accounts for reversibility within each
simulated person-day. All of the empirical data regarding time and
amounts consumed (and corresponding exposures based on the
corresponding residues) from the CSFII survey are used, along with the
half-life to assess an equivalent persisting dose that produced the
peak inhibition expected over the course of that day. This is a
reasonable assumption for food alone; since the time between exposure
events across 2 days is relatively high (compared to the half-life)--
most children (>9 months) tend to sleep through the night--and the time
between dinner and breakfast the following morning is long enough it is
reasonable to ``ignore'' persisting effects from the previous day. A
single day exposure model will underestimate the persisting effects
from drinking water exposures (formula) among infants, and newborns in
particular (<3 months), since newborns tend to wake up every 2 to 4
hours to feed. Any carry over

effects may be important, especially if exposures from the previous day
are relatively high, since the time between the last feeding (formula)
of the day and the first feeding of the subsequent day is short. A
single day model also does not account for the effect of seasonal
variations in drinking water concentrations, which will make this
effect more pronounced during the high use season (i.e., the time of
year when drinking water concentrations are high). Based on these
analyses, the Agency concludes that the current exposure assessment
methods used in the carbofuran dietary assessment provide realistic and
high confidence estimates of risk to carbofuran exposure through food
and water.

F. Response to FMC Comments on the Final Rule

    FMC's comments raised a range of issues. Those issues are not
summarized here because FMC basically refilled many of its comments as
objections without modifying them in response to EPA's decision in the
final rule. In addition, FMA submitted a an alternate risk analysis
purporting to show that aggregate carbofuran exposures to children
would be safe. However, FMC failed to provide the data and details of
that assessment to the Agency. They also failed to provide several
critical components that served to support key inputs into that
assessment; and for several of these, EPA was unable to replicate the
claimed results based on the information contained in the comments. In
the absence of such critical components, the Agency was unable to
accept the validity or utility of the analyses, let alone rely on the
results.
    Nonetheless, based on the summary descriptions provided in the
registrant's comments, EPA concluded that the risk analyses contained a
critical flaw. The commenters' determination of safety rests on the
presumption that under real world conditions, events will always occur
exactly as hypothesized by the multiple assumptions in their
assessment. For example, the comments assumed, despite all available
evidence to the contrary, that children would not be appreciably more
sensitive to carbofuran's effects than adults. They assumed that
carbofuran's effects will be highly reversible, and that children will
be uniformly sensitive, such that the effects will be adequately
accounted for by the assumption of a 150-minute half-life, despite the
fact that children are not uniformly sensitive. They further assumed
that there would be no carry over effect from the preceding day's
exposures for infants. They assumed that the cancellation of use on
alfalfa would reduce carbofuran residues in milk by over 70%, even
though many cows' diet consists primarily of corn. They assumed that
residues would decrease between 19% and 23% as a result of the buffer
requirements on the September 2008 label, even though the label does
not require the use of all of the recommended ``best management
practices'' (e.g., no requirements regarding swath displacement), and
applicators do not universally use such practices in the absence of any
requirement. They assumed that average ground water pH adequately
characterizes the temporal and spatial heterogeneity common in most
areas, despite the available evidence to the contrary. Finally, they
assumed that the percent of the crop treated in any watershed would
never exceed 5%, despite varying pest pressures, consultant
recommendations, and individual grower decisions. Leaving aside that
EPA believes most, if not all of these assumptions are not supported by
the available evidence described throughout the final rule, the
probability of all these assumptions always simultaneously holding true
under real world conditions is unreasonably low, and certainly does not
approach the degree of certainty necessary for EPA to conclude that
children's exposures will be safe.
    Determining whether residues will be safe for U.S. children is not
a theoretical paper exercise; it cannot suffice to hypothesize a unique
set of circumstances that make residues ``fit in the box.'' There must
be a reasonable certainty that under the variability that exists under
real world conditions, exposures will be ``safe.'' EPA's assessments
incorporate a certain degree of conservatism precisely to account for
the fact that assumptions must be made that may not prove accurate.
This consideration is highly relevant for carbofuran, because as
refined as EPA's assessments are, areas of uncertainty remain with
regard to carbofuran's risk potential. For example, a recent
epidemiological study reported that 45% of maternal and cord blood
samples in a cohort of New York City residents of Northern Manhattan
and the South Bronx between 2000 and 2004, contained low, but
measurable residues of carbofuran (Ref. 88). The Agency is currently
unable to account for the source of such sustained exposures at this
frequency.
    A further consideration is that the risks of concern are acute
risks to children. For acute risks, the higher values in a
probabilistic risk assessment are often driven by relatively high
values in a few exposures rather than relatively lower values in a
greater number of exposures. This is due to the fact that an acute
assessment looks at a narrow window of exposure where there are
unlikely to be a great variety of consumption sources. Thus, to the
extent that there is a high exposure it will be more likely due to a
high residue value in a single consumption event. Additionally
worrisome in this regard is that carbofuran is a highly potent (i.e.,
has a very steep dose-response curve), acute toxicant, and therefore
any aPAD exceedances are more likely to have greater significance in
terms of the potential likelihood of actual harm. For all of these
reasons, EPA determined that the existing carbofuran tolerances did not
meet the FFDCA safety standard, and should therefore be revoked.

VI. Response to Objections and Requests for Hearing

A. Overview

    Petitioners raised several objections that correspond to four basic
categories of issues. The first category of objections and hearing
requests relates to challenges to EPA's selection of the appropriate
children's safety factor. In this category of issues, they raise
primarily two claims: (1) That EPA's scientific basis for retaining a
4X safety factor is flawed, and (2) the statistical calculations
supporting the 4X safety factor are flawed, and based on faulty
assumptions. The second category of issues relate to the manner in
which EPA conducted its assessment of the exposure from carbofuran
through drinking water sources. In this regard, all of their objections
fall within three basic categories of issues: (1) EPA should have
accounted for a more realistic percent of the crop treated (PCT) in its
surface water modeling; (2) EPA's ground water concentration estimates
are not based on the best available data, but on obsolete data and
overly conservative assumptions; and (3) FMC's new label restrictions
and revised terms of registration will ensure that drinking water
concentrations will not exceed 1.1 ppb. The third category of issues
relates to the manner in which EPA conducted its dietary risk
assessment. Under this category, the objections and hearing requests
raise four primary issues: (1) Petitioners challenge the way in which
EPA's risk assessments accounted for individuals to recover from the
effects of carbofuran between exposures; (2) EPA should have relied on
the carbofuran human study and therefore use of the default 10X
interspecies factor is inconsistent with

the ``best available data; (3) the import tolerances by themselves are
safe and EPA should have retained them even if EPA believed tolerances
associated with the domestic uses were unsafe; and (4) Petitioners
claim that the combined food and water exposures are safe, based on
FMC's drinking water estimates of a 1.1 ppb maximum concentration,
which are guaranteed by new label restrictions submitted as part of
objections. Finally, Petitioners raise one legal objection
unaccompanied by a hearing request. They argue that EPA lacks authority
to limit issues and supporting information that can be raised in
objections and hearing to those raised in earlier comments.
    EPA denies each of the Petitioners' objections as well as their
hearing requests. In the first instance, EPA denies Petitioners'
objections and their hearing requests because the objections are
inextricably intertwined with proposed changes to carbofuran's FIFRA
registration that were not submitted until after publication of the
final tolerance revocation rule. Objections to EPA's decision based on
FIFRA registration amendments proposed after EPA's decision are
irrelevant, and thus immaterial, to a challenge to EPA's decision (See
Unit VI.C.). Secondly, an individual analysis of Petitioners'
objections and hearing requests leads to the same conclusion for the
reasons summarized below.
    The Petitioners' hearing requests fail to meet the statutory and
regulatory requirements for holding a hearing. In most cases, EPA has
denied the request on the grounds that the objection is irrelevant, and
therefore immaterial, with regard to EPA's final tolerance revocation
regulation. In particular, many claims are immaterial because they
largely restate the claims in their combined comments on EPA's proposed
rule without challenging the substance or even responding to EPA's
explanations for the reasons that EPA declined to adopt the approaches
or otherwise make the revisions suggested by the Petitioners in their
comments. These claims are irrelevant to the determinations reached in
the final rule. In several instances, EPA concluded that Petitioners
evidentiary proffer was inadequate, because the data and information
submitted, even if accurate, would be insufficient to justify the
factual determination urged, or to resolve one or more of the issues in
their favor. Further, in many cases, the evidence submitted constituted
mere allegations and general denials and contentions, which EPA
regulations expressly provide to be insufficient to justify a hearing.
In addition, many of Petitioners' claims do not present genuine and
substantial issues of fact and/or are immaterial to the relief
requested.
    On the merits, the majority of Petitioners' objections are denied
for substantially the same reasons given in EPA's final rule and
response to comments. As noted, many of Petitioners' objections are
simply their recycled comments which do not address the conclusions
reached by EPA in the final rule. To the extent a response is even
needed to such a stale claim, it is provided in the final rule and the
response to comments.
    The remainder of this Unit is organized in the following manner.
Unit VI.B describes in greater detail the requirements pertaining to
when it is appropriate to grant a hearing request. In Unit VI.C, EPA
generally denies all of Petitioners' objections and hearing requests.
Unit VI.D provides EPA's response to the Petitioners legal objection
that EPA lacks the legal authority to limit the issues and supporting
information that can be raised in an objection and hearing to those
raised in comments on the proposed rule. Units VI. G and I provide
Petitioners' claims regarding EPA's risk assessment. EPA's conclusions
on the hearing requests and objections are summarized in Unit VI.K.
    EPA has adopted a 4-part format in Units VI.E through I. for
explaining its ruling on each of the subissues EPA identified in the
objections. First, the Petitioners' claim and any arguments or evidence
tendered to support that claim are described. Second, background
information on the claim is provided including whether and how the
claim was presented in Petitioners' comments and, if it was presented,
EPA's reasons for denying the claim in its final rule and response to
comments. Third, EPA explains its reasons for denying a hearing on that
claim. Finally, EPA explains its reasons for denying the claim on the
merits.

B. The Standard for Granting an Evidentiary Hearing

    EPA has established regulations governing objections to tolerance
rulemakings and tolerance petition denials and requests for hearings on
those objections. (40 CFR Part 178; 55 FR 50291 (December 5, 1990)).
Those regulations prescribe both the form and content of hearing
requests and the standard under which EPA is to evaluate requests for
an evidentiary hearing.
    As to the form and content of a hearing request, the regulations
specify that a hearing request must include: (1) A statement of the
factual issues on which a hearing is requested and the requestor's
contentions on those issues; (2) a copy of any report, article, or
other written document ``upon which the objector relies to justify an
evidentiary hearing;'' and (3) a summary of any other evidence relied
upon to justify a hearing. (40 CFR 178.27).
    The standard for granting a hearing request is set forth in section
178.32. That section provides that a hearing will be granted if EPA
determines that the ``material submitted'' shows all of the following:

    (1) There is a genuine and substantial issue of fact for
resolution at a hearing. An evidentiary hearing will not be granted
on issues of policy or law.
    (2) There is a reasonable possibility 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 or facts to the contrary. An evidentiary hearing
will not be granted on the basis of mere allegations, denials, or
general descriptions of positions and contentions, nor if the
Administrator concludes that the data and information submitted,
even if accurate, would be insufficient to justify the factual
determination urged.
    (3) Resolution of the factual issue(s) in the manner sought by
the person requesting the hearing would be adequate to justify the
action requested. An evidentiary hearing will not be granted on
factual issues that are not determinative with respect to the action
requested. For example, a hearing will not be granted if the
Administrator concludes that the action would be the same even if
the factual issue were resolved in the manner sought.

    (40 CFR 178.32(b)).
    This provision essentially imposes four requirements upon a hearing
requestor. First, the requestor must show it is raising a question of
fact, not one of law or policy. Hearings are for resolving factual
issues, not for debating law or policy questions. Second, the requestor
must demonstrate that there is a genuine dispute as to the issue of
fact. If the facts are undisputed or the record is clear that no
genuine dispute exists, there is no need for a hearing. Third, the
requestor must show that the disputed factual question is material--
i.e., that it is outcome determinative with regard to the relief
requested in the objections. Finally, the requestor must make a
sufficient evidentiary proffer to demonstrate that there is a
reasonable possibility that the issue could be resolved in favor of the
requestor. Hearings are for the purpose of providing objectors with an
opportunity to present evidence supporting their objections as the
regulation states, hearings will not be granted on the basis of ``mere
allegations, denials, or general

descriptions of positions or contentions.'' (40 CFR 178.32(b)(2)).
    EPA's hearing request requirements are based heavily on FDA
regulations establishing similar requirements for hearing requests
filed under other provisions of the FFDCA (53 FR 41126, 41129 (October
19, 1988)). FDA pioneered the use of summary judgment-type procedures
to limit hearings to disputed material factual issues and thereby
conserve agency resources. FDA's use of such procedures was upheld by
the Supreme Court in 1972, (Weinberger v. Hynson, Westcott & Dunning,
Inc., 412 U.S. 609 (1973)), and, in 1975, FDA promulgated generic
regulations establishing the standard for evaluating hearing requests
(40 FR 22950 (May 27, 1975)). It is these regulations upon which EPA
relied in promulgating its hearing regulations in 1990.
    Unlike EPA, FDA has had numerous occasions to apply its regulations
on hearing requests. FDA's summary of the thrust of its regulations,
which has been repeatedly published in the Federal Register in orders
ruling on hearing requests over the last 24 years, is instructive on
the proper interpretation of the regulatory requirements. That summary
states:

    A party seeking a hearing is required to meet a threshold burden
of tendering evidence suggesting the need for a hearing.' [] An
allegation that a hearing is necessary to sharpen the issues' or
fully develop the facts' does not meet this test. If a hearing
request fails to identify any evidence that would be the subject of
a hearing, there is no point in holding one.
    A hearing request must not only contain evidence, but that
evidence should raise a material issue of fact concerning which a
meaningful hearing might be held. [] FDA need not grant a hearing in
each case where an objection submits additional information or
posits a novel interpretation of existing information. [] Stated
another way, a hearing is justified only if the objections are made
in good faith and if they ``draw in question in a material way the
underpinnings of the regulation at issue.'' Finally, courts have
uniformly recognized that a hearing need not be held to resolve
questions of law or policy

    (49 FR 6672, 6673 (February 22, 1984); 72 FR 39557, 39558 (July 19,
2007) (citations omitted)).
    EPA has been guided by FDA's application of its regulations in this
proceeding. Congress confirmed EPA's authority to use summary judgment-
type procedures with hearing requests when it amended FFDCA section 408
in 1996. Although the statute had been silent on this issue previously,
the FQPA added language specifying that when a hearing is requested,
EPA ``shall * * * hold a public evidentiary hearing if and to the
extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)). This
language grants EPA broad discretion to determine whether a hearing is
``necessary to receive factual evidence'' to objections (H.R. Rep. No.
104-669, at 49 (1996)).

C. General Denial of Objections and Hearing Requests

    Petitioners' objections and hearing requests are denied in their
entirety as irrelevant, and therefore immaterial, to EPA's
determination in the May 15, 2009 final rule that the carbofuran
tolerances were unsafe and could not be sustained under FFDCA section
408. In that final rule, EPA assessed the risks from carbofuran based
on existing uses of carbofuran, as modified by all use restrictions
proposed by FMC. EPA concluded that the carbofuran tolerances
substantially exceeded the FFDCA safety standard, particularly as to
infants and children.
    Petitioners' objections and hearing requests as to that final rule
disclose on their face their irrelevance to the conclusions reached in
the May 15, 2009 final rule. As Petitioners summarize their objections
on the first page of their submission:

    Petitioners disagree that the carbofuran tolerances are unsafe
and argue that the available scientific data show that there is a
reasonable certainty of no harm to human health from the continued
use of carbofuran for certain specific uses and related tolerances
under the terms for reregistration proposed by Petitioners.

    (Objections at 1) (footnote omitted) (emphasis added). As
Petitioners' footnote to this sentence reveals, however, the proposed
terms for FIFRA reregistration referenced by Petitioners include
significant terms submitted to EPA on June 29, 2009, 44 days after
publication of the final rule revoking carbofuran's FFDCA tolerances.
In fact, the body of Petitioners' objections show that FMC's June 29,
2009 proposed FIFRA registration amendments are inextricably
intertwined with the claims made in the objections. Thus, Petitioners
are actually not objecting to the conclusions in EPA's final rule;
rather, they are suggesting that EPA might reach a different result in
a different factual scenario.
    Objections, however, must be directed ``with particularity [at] the
provisions of the regulation or order deemed objectionable.'' 21 U.S.C.
346a(g)(2). The key here is that a party must file particularized
objections to--that is, identify some type of error in--a specific
regulatory decision. In no sense, however, can it be claimed that EPA
erred, or that there is something objectionable, in its May 15, 2009
file rule because EPA did not consider a proposed revision to the terms
of the carbofuran registration that had not yet been made. EPA need not
shoot at a moving target, much less a target that is not in existence.
Therefore, Petitioners' objections are irrelevant, and thus immaterial,
to the May 15, 2009 final rule; they are based on hypothetical terms of
carbofuran use not before the Agency as it made its determination in
that final rule.
    Moreover, it is not as if Petitioners' proposed terms for
carbofuran use are simple, straightforward use deletions that could be
immediately effectuated. While such a proposal is still irrelevant as a
challenge to a prior EPA determination, such a proposal might lead EPA
to expeditiously modify its action. Rather, Petitioners have proposed
an unprecedented scheme involving FMC playing a role as a middleman
between EPA and growers to ensure that carbofuran use in no one area
exceeds a certain percentage of the cropped area. FMC has properly
filed proposed amendments to its FIFRA registration, which would
incorporate these new restrictions on carbofuran use and EPA will
review these proposals consistent with the substantive and procedural
requirements of FIFRA. At such time as these new terms of registration
are determined by EPA to meet the standard for registration, and not
before, would it be appropriate for EPA to consider whether the
tolerance revoked by the May 15, 2009 rule should be re-established.
    Finally, Petitioners argue that it can raise its proposed terms of
carbofuran use because EPA cannot limit them from putting forward new
issues in a hearing. As explained below, EPA believes Petitioners have
misconstrued the law on this point. However, even assuming for the sake
of argument that Petitioners are correct that new issues can be raised
at a hearing on objections, Petitioners admit that any newly raised
issues must meet the standard of relevance. As explained above,
however, objections based on terms or FIFRA registration proposed after
EPA's final rule are irrelevant to the correctness of EPA's
determination in that final rule.
    EPA has nonetheless evaluated each of Petitioners' objections and
hearing requests and determined that there are alternate grounds for
denying them. (See Units VI.E through I). EPA has undertaken this
analysis for all of the objections despite the fact that it is not at
all clear that those of Petitioners'

claims which appear to be unrelated to FMC's recently proposed
registration amendments would either individually or collectively
change EPA's safety determination for the carbofuran tolerances given
the relatively high level of risk estimated for the carbofuran
tolerances in the final revocation rule. Petitioners have certainly not
provided any road map as to how a safety finding could be made absent
FMC's recently-proposed registration amendments. The failure to make
such a showing is further justification for EPA's denial of
Petitioners' objections and hearing requests.

D. Response to Petitioners' Objection That EPA Lacks the Authority To
Limit the Issues That May Be Raised in Objections and Hearing Requests

    1. Response to Legal Issue. Petitioners claim that EPA lacks the
authority to restrict the issues that may be raised as part of their
objections. Specifically, they challenge EPA's interpretation that the
failure to raise issues or provide information during the comment
period on the proposed rule bars consideration of such issues or
evidence as part of submitted objections or hearings. Petitioners make
two arguments in support of this contention: (1) That neither FFDCA
section 408(g) on its face nor EPA's regulations implementing FFDCA
section 408(g) limit the issues that can be raised in objections, or in
any hearing; and (2) that even though the rulemaking phase is governed
by 553 of the Administrative Procedure Act (APA), the hearing must be
held in accordance with APA sections 556 and 557, which requires that
the ``exclusive record for decision must consist of testimony and
exhibits received at the hearing, as well as other papers filed in the
hearing proceeding'' (Obj at 64). On this basis, the Petitioners
conclude that all of the cases cited in the Final Rule requiring
parties to raise all issues and information on which they intend to
rely in subsequent proceedings are inapplicable.
    These arguments are premised on several fundamental
misconstructions of the FFDCA section 408 and the APA. None of the
cases they cite address the specific question of whether and how the
requirements of section 553 of the APA apply to FFDCA section 408. And
for many of these cases, Petitioners misquote the cases, misinterpret
the holdings, or misconstrue language taken out of context.
    Petitioners' first argument, that neither section 408(g) nor EPA's
regulations limit the issues that can be raised in objections or in any
hearing, is incorrect and misses the point. As discussed at length in
the Final Rule, the provisions of 408(g) are not to be viewed in
isolation, but as part of a coherent statutory structure inextricably
linked to the FFDCA's informal rulemaking procedures and section 553 of
the APA. Petitioners concede that FFDCA section 408 establishes an
informal rulemaking process (Obj at 62-63). As an informal rulemaking,
the process is governed by section 553 of the APA and the case law
interpreting these requirements, except to the extent that section 408
provides otherwise.\5\ In this regard, it is well established that the
failure to raise factual or legal issues during the comment period of a
rulemaking constitutes waiver of the issues in further proceedings.
E.g., Forest Guardians v. U.S. Forest Service, 495 F.3d 1162, 1170-1172
(10th Cir. 2007) (Claim held waived where commenters ``failed to
present its claims in sufficient detail to allow the agency to rectify
the alleged violation''); Nuclear Energy Institute v. EPA, 373 F.3d
1251, 1290-1291 (DC Cir. 2004) (``To preserve a legal or factual
argument, we require its proponent to have given the agency a `fair
opportunity' to entertain it in the administrative forum before raising
it in the judicial forum.'') Native Ecosystems Council v. Dombeck, 304
F.3d 886, 889-900 (9th Cir. 2002) (Purpose of requirement that issues
not presented at administrative level are deemed waived is to avoid
premature claims and ensure that agency be given a chance to bring its
expertise to bear to resolve a claim); Kleissler v. U.S. Forest
Service, 183 F.3d 196, 202 (3d Cir. 1999) (Policy underlying exhaustion
requirement is that ``objections and issues should first be reviewed by
those with expertise in the contested subject area''); National
Association of Manufacturers v. U.S. DOI, 134 F.3d 1095, 1111 (DC Cir.
1998) (``We decline to find that scattered references to the services
concept in a voluminous record addressing myriad complex technical and
policy matters suffices to provide an agency like DOI with a `fair
opportunity' to pass on the issue''); Linemaster Switch Corporation v.
EPA, 938 F.2d 1299, 1305-1306 (DC Cir. 1991) (declining to consider in
challenge to final rule, data alluded to in comments but not submitted
during the comment period, and information submitted to EPA office that
was not developing the rule).
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    \5\ For example, section 408(d) allows the Agency to proceed to
a final rule after publication of a submitted petition, rather than
requiring publication of a proposal.
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    Moreover, EPA clearly stated in the proposed rule that the Agency
considered that the usual requirements applicable to informal
rulemakings would remain applicable in this informal rulemaking. The
proposal explicitly noted that ``[i]f you anticipate that you may wish
to file objections on the final rule, you must raise those issues in
your comments on this proposal. EPA will treat as waived, any issue not
originally raised in comments on this proposal'' (73 FR 44,865 (July
31, 2008)).
    The fact that FFDCA section 408 in certain limited circumstances
supplements the informal rulemaking with a hearing does not
fundamentally alter the requirements applicable to informal
rulemakings. Nor, as discussed below, does it convert this into a
formal rulemaking, subject to the exception in section 553. The FFDCA
section 408 establishes a unique statutory structure with multiple
procedural stages, and delegates to EPA the discretion to determine the
implementation that best achieves the statutory objectives.