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Mesotrione - Pesticide Tolerance 6/01

ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-301138; FRL-6787-7]
RIN 2070-AB78
Mesotrione; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes a tolerance for residues
of mesotrione, 2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-
cyclohexanedione, in or on field corn. Syngenta Crop Protection Inc.
requested this tolerance under the Federal Food, Drug, and Cosmetic
Act, as amended by the Food Quality Protection Act of 1996.

DATES: This regulation is effective June 21, 2001. Objections and
requests for hearings, identified by docket control number OPP-301138,
must be received by EPA on or before August 20, 2001.

ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. To ensure proper receipt by EPA, your objections and
hearing requests must identify docket control numberOPP-301138 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Joanne Miller,Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460;
telephone number: 703-305-6224; and e-mail address:

Miller.Joanne@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                 Examples of Potentially
             Categories                 NAICS       Affected Entities
------------------------------------------------------------------------
Industry                                    111  Crop production
                                            112  Animal production
                                            311  Food manufacturing
                                          32532  Pesticide manufacturing
------------------------------------------------------------------------

[[Page 33188]]

    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 the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply t certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

    1. Electronically.You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select "Laws and
Regulations", "Regulations and Proposed Rules," and then look up the
entry for this document under the "Federal Register---Environmental
Documents." You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm. A
frequently updated
electronic version of 40 CFR part 180 is available at http://
www.access.gpo.gov/nara/cfr/cfrhtml_180/Title_40/40cfr180_00. html, a
beta site currently under development.
    2. In person. The Agency has established an official record for
this action under docket control number OPP-301138. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of May 29, 1998 (63 FR 29401) (FRL-5791-2),
EPA issued a notice pursuant to section 408 of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food Quality
Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the
filing of a pesticide petition (PP 8F4954) for tolerance by Zeneca Ag
Products, 1800 Concord Pike, Wilmington, DE 19850-5458. This notice
included a summary of the petition prepared by Zeneca Ag Products, the
registrant. There were no comments received in response to the notice
of filing. The petition was subsequently transferred to Syngenta Crop
Protection Inc., 410 Swing Road, PO Box 18300, Greensboro, NC 27419-
8300.
    The petition requested that 40 CFR part 180 be amended by
establishing a tolerance for residues of the herbicide 2-[4-
(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione, in or on the raw
agricultural commodities field corn, field corn fodder and field corn
forage at 0.01 part per million (ppm). EPA is editorially correcting
the tolerances expression to read: field corn grain, field corn forage
and field corn stover at 0.01 ppm.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is "safe." Section
408(b)(2)(A)(ii) 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)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to "ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue...."
    EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of mesotrione, 2-[4-
(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione, in or on field
corn grain, field corn forage and field corn stover at 0.01 ppm. EPA's
assessment of exposures and risks associated with establishing the
tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by mesotrione are
discussed in the following Table 1 as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.

                                Table 1.--Subchronic, Chronic, and Other Toxicity
---------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type Results
---------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity NOAEL = 0.41/0.47 milligram (mg)/kilogram
                                          rodents (rat) (kg)/day (males [M]/females [F])
LOAEL = 0.63/0.71 mg/kg/day (M/F), based
upon corneal lesion in males
---------------------------------------------------------------------------------------------------------

870.3100                                 90-Day oral toxicity NOAEL = 0.09/0.10 mg/kg/day (M/F)
                                          rodents (rat)
LOAEL = 11/13 mg/kg/day (M/F), based upon
corneal abnormalities in both sexes and
decreased body weight gain in males
---------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity NOAEL = 1212/1537 mg/kg/day (M/F)
                                          rodents (mouse)
LOAEL greater than (>) 1212/1537 mg/kg/day
(M/F). No effects noted
---------------------------------------------------------------------------------------------------------
870.3150                                 90-Day oral toxicity in NOAEL = 1,000 mg/kg/day (M/F)
                                          nonrodents (dog)
LOAEL > 1,000 mg/kg/day (M/F) No effects
                                                                      noted
---------------------------------------------------------------------------------------------------------
870.3200                                 21/28-Day dermal toxicity NOAEL = 1,000 mg/kg/day (M/F)
                                          (rabbit)
LOAEL > 1,000 mg/kg/day (M/F). No systemic
effects noted
---------------------------------------------------------------------------------------------------------
870.3700a                                Prenatal developmental in Maternal NOAEL = 100 mg/kg/day

                                          rodents (rat)
LOAEL = 300 mg/kg/day, based upon decreased
maternal body weight gains during
treatment and decreased food consumption
Developmental NOAEL was not established
LOAEL = 100 mg/kg/day, based upon delays in
skeletal ossification and changes in
manuspes ossification assessments
---------------------------------------------------------------------------------------------------------
870.3700a                                Prenatal developmental in Maternal NOAEL = 600 mg/kg/day
                                          rodents (mouse)
LOAEL >600 mg/kg/day; No effects noted
Developmental NOAEL = 150 mg/kg/day
LOAEL = 600 mg/kg/day, based upon decreased
ossification of the cervical vertebrae
                                                                      centra
---------------------------------------------------------------------------------------------------------
870.3800                       Reproduction and fertility Parental/Systemic NOAEL was not established
                                          effects (rat)
LOAEL = 0.3 mg/kg/day (M/F), based upon
significantly increased plasma tyrosine
levels and increased liver weights in F2
                                                                      males
Offspring/Systemic NOAEL not established
LOAEL = 0.3 mg/kg/day (M/F), based upon
significantly increased plasma tyrosine
levels in F2 male pups
Reproductive NOAEL = 0.3 mg/kg/day
LOAEL = 1.1/1.2 mg/kg/day (M/F), based upon
decreased F2 mean litter size
---------------------------------------------------------------------------------------------------------
870.3800                       Reproduction and fertility Parental/Systemic NOAEL = 10.1/11.7 mg/kg/
                                          effects (mouse)             day (M/F)
LOAEL = 71.4/82.5 mg/kg/day (M/F), based
upon increased kidney weights and
tyrosinemia in the and F1 males
Offspring/Systemic NOAEL not established
LOAEL = 2.1/2.4 mg/kg/day (M/F), based upon
tyrosinemia and ocular discharge in the F1
and F2 offspring
Reproductive NOAEL = 1455.5/1652.3 mg/kg/
                                                                      day (M/F)
LOAEL > 1455.5/1652.3 mg/kg/day
----------------------------------------------------------------------------------------------------------

870.4100a                                Chronic toxicity rodents NOAEL = 56.2/72.4 mg/kg/day (M/F)
                                          (mouse)
LOAEL = 1114/1494.5 mg/kg/day (M/F), based
upon decreases in body weight gain and
food utilization in males
----------------------------------------------------------------------------------------------------------
870.4100b                                Chronic toxicity dogs NOAEL was not established
LOAEL = 10 mg/kg/day, based upon evidence
of tyrosinemia in both sexes and increased
incidence of erythrophagocytosis in the
mesenteric lymph nodes of females
----------------------------------------------------------------------------------------------------------
870.4300                                 Combined chronic toxicity/ NOAEL was not established
                                          carcinogenicity rodents
                                          (rat)
NOAEL = 0.16/0.19 mg/kg/day (M/F) ocular
lesions only]
LOAEL = 0.16/0.19 mg/kg/day based kidney
and liver weights or hepatocyte fat
vacuolation in males
LOAEL = 0.48/0.57 mg/kg/day (M/F), based
upon ocular lesions, increases in kidney
and liver weights, and hepatocyte fat
vacuolation in females
No evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------
870.4300                                 Carcinogenicity mice NOAEL = 49.7/63.5 mg/kg/day (M/F)

LOAEL = 898/1103 mg/kg/day (M/F), based
upon decreased body weight, body weight
gain, and food efficiency in males
No evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------
870.5100                        Gene Mutation reverse gene There was no evidence of induced mutant
                                 mutation assay in colonies over background
                                 bacteria
----------------------------------------------------------------------------------------------------------
870.5300                        Gene Mutation in vitro There were no treatment-related increases
                                 forward gene mutation in mutant frequency in the presence or
                                 assay in mouse lymphoma absence of S9 activation
                                 cells
----------------------------------------------------------------------------------------------------------
870.5375                        Cytogenetics in vitro Not clastogenic with S9 activation and
                                 mammalian cytogenetics equivocal for clastogenic activity without
                                 assay S9 activation
----------------------------------------------------------------------------------------------------------
870.5395                            bone marrow micronucleus There was no significant increase in the
                                          assay frequency of micronucleated polychromatic
erythrocytes in bone marrow after any
treatment time.
----------------------------------------------------------------------------------------------------------
870.6200a                                Acute neurotoxicity NOAEL = 2,000 mg/kg/day (M/F)
                                          screening battery
LOAEL > 2,000 mg/kg/day (M/F)
No effects noted
----------------------------------------------------------------------------------------------------------
870.6200b                                Subchronic neurotoxicity NOAEL = 0.20/0.23 mg/kg/day (M/F)
                                          screening battery
LOAEL = 8.25/9.29 mg/kg/day (M/F), based
upon corneal opacities and/or
vascularization of the cornea of the eye
                                                                      in males
----------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism rat Mesotrione was readily absorbed and
distributed in the body. Tissue
distribution was about the same in both
sexes, although one study showed higher
residues in the kidneys in females, with
the highest residues of the test compound
in the liver and kidney. Higher doses
resulted in higher residues in the liver
and kidney, while repeated doses resulted
in reduced accumulation of residues in all
tissues. Levels of radioactivity in
tissues of iv-dosed animals were
essentially the same as in orally-dosed
animals. Over 50% of the administered dose
was excreted in the urine in both sexes
and around 25% was excreted in the feces
within 72 hours. Females exhibited
slightly higher total urinary excretion
than males, but total fecal excretion was
about the same in both sexes. Increasing
the dose or repeated doses had little
effect on the pattern of excretion in both
sexes. The overall pattern of excretion
was similar between orally-dosed and iv-
dosed rats. The metabolite profile was
similar between the sexes in each group
and between the single-dosed and repeated-
dosed animals. The parent compound,
mesotrione, was the major component
identified in the urine (> 47%) and feces
(> 55%). Minor metabolites identified were
MNBA, AMBA, 5-hydroxymesotrione, and 4-
hydroxymesotrione.
--------------------------------------------------------------------------------------------------------
870.7485                   Metabolism mouse Metabolism in the mouse was very similar to
the rat (above) except that males had
slightly increased total fecal excretion
when compared to females and, females in
the low-dose group excreted higher (1.5x)
levels of parent compound in the urine
than males. Free mesotrione was the major
component in the urine and feces ( 50% of
the dose). Minor components in the fecal
extracts included AMBA and MNBA.
--------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intra species differences. A UF of
3 is used if no NOAEL was achieved in the toxicology study.
    For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor.
    For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the
LOC is 100. To estimate risk, a ratio of the NOAEL to exposures (margin
of exposure (MOE) = NOAEL/exposure) is calculated and compared to the
LOC.
    The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as 1 x 10**-6 or one in a million).
Under certain specific circumstances, MOE calculations will be used for
the carcinogenic risk assessment. In this non-linear approach, a
"point of departure" is identified below which carcinogenic effects
are not expected. The point of departure is typically a NOAEL based on
an endpoint related to cancer effects though it may be a different
value derived from the dose response curve. To estimate risk, a ratio
of the point of departure to exposure (MOE-cancer = point of
departure/exposures) is calculated. A summary of the toxicological
endpoints for mesotrione used for human risk assessment is shown in the
following Table 2:

      Table 2.--Summary of Toxicological Dose and Endpoints for Mesotrione for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 FQPA SF* and Level of
          Exposure Scenario               Dose Used in Risk Concern for Risk     Study and Toxicological
                                            Assessment, UF Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary all populations          Not Applicable           Not Applicable           No appropriate study
available.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations        LOAEL= 2.1 mg/kg/day;    FQPA SF = 10X; cPAD =    Reproduction Study -
                                        UF = 300 [10 x 3]; chronic RfD/FQPA SF =    mouse
                                        Chronic RfD = 0.007 mg/ 0.0007 mg/kg/day
                                        kg/day
Offspring LOAEL = 2.1
mg/kg/day based upon
tyrosinemia in F1 and
F2a offspring and
ocular discharge in F1
pups**.
----------------------------------------------------------------------------------------------------------------

Oral, Short-term (1-7 days)                   No residential uses. An endpoint was not proposed/selected.
 (Residential)
----------------------------------------------------------------------------------------------------------------
Oral, Intermediate-term (1 week -             No residential uses. An endpoint was not proposed/selected.
 several months) (Residential)
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      not likely               Not Applicable           Acceptable oral rat and
mouse carcinogenicity
studies; no evidence
of carcinogenic or
mutagenic potential.
----------------------------------------------------------------------------------------------------------------
\*\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
  unique to the FQPA.
\**\ Plasma tyrosine levels were increased in the rat, mouse and dog in the chronic and reproduction studies in
  which levels were measured. The ocular, liver and kidney effects are believed to be mediated by the high
  tyrosine levels in the blood caused by inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD).
  Even though the rat is the most sensitive species to this effect compared to the dog and the mouse, EPA
  concludes that the mouse is a more appropriate model for assessing human risk than is the rat.

C. Exposure Assessment

     1. Dietary exposure from food and feed uses. No tolerances have
been previously established (40 CFR part 180) for residues of
mesotrione in or on any variety of raw agricultural commodities. Risk
assessments were conducted by EPA to assess dietary exposures from
mesotrione in food as follows:
     i. Acute exposure. Acute dietary risk assessments are performed
for a food-use pesticide if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one day
or single exposure. No appropriate study available show any acute
dietary effects of concern.
     ii. Chronic exposure. In conducting this chronic dietary risk
assessment the Dietary Exposure Evaluation Model (DEEM)
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. The following assumptions were made for the chronic
exposure assessments: residue levels are at the recommended tolerances
for field corn, and 100% of the crop field corn is treated with
mesotrione. The %cPAD for the general U.S. population is 1.8% and for
the most sensitive population subgroups, All Infants (< 1 year old), is
4.3%.
     iii. Cancer. Acceptable oral rat and mouse carcinogenicity studies
showed no evidence of carcinogenic or mutagenic potential.

    2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for mesotrione in drinking water.
Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of mesotrione.
    The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW, which predicts pesticide concentrations in groundwater. In
general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS
(a tier 2 model) for a screening-level assessment for surface water.
The GENEEC model is a subset of the PRZM/EXAMS model that uses a
specific high-end runoff scenario for pesticides. GENEEC incorporates a
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir
environment in place of the previous pond scenario. The PRZM/EXAMS
model includes a percent crop area factor as an adjustment to account
for the maximum percent crop coverage within a watershed or drainage
basin.
    None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The
primary use of these models by the Agency at this stage is to provide a
coarse screen for sorting out pesticides for which it is highly
unlikely that drinking water concentrations would ever exceed human
health levels of concern.
    Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead drinking
water levels of comparison (DWLOCs) are calculated and used as a point
of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to mesotrione they are further
discussed in the aggregate risk sections below.
    Based on the GENEEC (Version 1.2) and SCI-GROW models the estimated
environmental concentrations (EECs) of mesotrione for acute exposures
are estimated to be 20 parts per billion (ppb) for surface water and
0.15 ppb for ground water. The EECs for chronic exposures are estimated
to be 4.3 ppb for surface water and 0.15 ppb for ground water.
    3. From non-dietary exposure. The term "residential exposure" is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). Mesotrione is not
registered for use on any sites that would result in residential
exposure.
    4. Cumulative exposure to substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider "available information" concerning the cumulative effects of
a particular pesticide's residues and "other substances that have a
common mechanism of toxicity."

    EPA does not have, at this time, available data to determine
whether mesotrione has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
mesotrione does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that mesotrione has a common mechanism of toxicity
with other substances. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).

D. Safety Factor for Infants and Children

    1. Safety factor for infants and children--i. In general. FFDCA
section 408 provides that EPA shall apply an additional tenfold margin
of safety for infants and children in the case of threshold effects to
account for prenatal and postnatal toxicity and the completeness of the
data base on toxicity and exposure unless EPA determines that a
different margin of safety will be safe for infants and children.
Margins of safety are incorporated into EPA risk assessments either
directly through use of a margin of exposure (MOE) analysis or through
using uncertainty (safety) factors in calculating a dose level that
poses no appreciable risk to humans.
    ii. Prenatal and postnatal sensitivity. There is quantitative
evidence of increased susceptibility demonstrated in the oral prenatal
developmental toxicity studies in rats, mice, and rabbits. Delayed
ossification was seen in the fetuses at doses below those at which
maternal toxic effects were noted. Maternal toxic effects in the rat
were decreased body weight gain during treatment and decreased food
consumption and in the rabbit, abortions and GI effects.
    2. Conclusion. The FQPA safety factor (10x) is retained in
assessing the risk posed because there is quantitative evidence of
increased susceptibility of the young exposed to mesotrione in the
prenatal developmental toxicity studies in mice, rats, and rabbits and
in the multi-generation reproduction study in mice, there is
qualitative evidence of increased susceptibility of the young exposed
to mesotrione in the multi-generation reproduction study in rats; and a
Developmental Neurotoxicity Study is required to assess the effects of
tyrosinemia on the developing nervous system exposed to mesotrione.

E. Aggregate Risks and Determination of Safety

    To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates drinking
water level of comparison (DWLOCs) which are used as a point of
comparison against the model estimates of a pesticide's concentration
in water (EECs). DWLOC values are not regulatory standards for drinking
water. DWLOCs are theoretical upper limits on a pesticide's
concentration in drinking water in light of total aggregate exposure to
a pesticide in food and residential uses. In calculating a DWLOC, the
Agency determines how much of the acceptable exposure (i.e., the PAD)
is available for exposure through drinking water [e.g., allowable
chronic water exposure (mg/kg/day) = cPAD - (average food + residential
exposure)]. This allowable exposure through drinking water is used to
calculate a DWLOC.
    A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg
(child). Default body weights and drinking water consumption values
vary on an individual basis. This variation will be taken into account
in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
acute, short-term, intermediate-term, chronic, and cancer.

    When EECs for surface water and groundwater are less than the
calculated DWLOCs, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which OPP has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because OPP considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, OPP will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
    1. Acute risk. Acute doses and endpoints were not selected for the
general U.S. population (including infants and children) or the females
13-50 years old population subgroup for mesotrione; therefore, an acute
dietary exposure analysis was not performed.
    2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
mesotrione from food will utilize 1.8% of the cPAD for the U.S.
population, 4.3% of the cPAD for
All Infants (< 1 year old) and 4.2% of the cPAD for Children 1-6 years
old. There are no residential uses for mesotrione that result in
chronic residential exposure to mesotrione.

               Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to mesotrione
----------------------------------------------------------------------------------------------------------------
Surface       Ground
              Population Subgroup                cPAD mg/kg/     % cPAD     Water EEC    Water EEC     Chronic
                                                     day (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                       0.0007 1.8          4.3         0.15           24
----------------------------------------------------------------------------------------------------------------
All infants (< 1 year old)                            0.0007 4.3          4.3         0.15          6.7
----------------------------------------------------------------------------------------------------------------
Children (1-6 years old)                              0.0007 4.2          4.3         0.15          6.7
----------------------------------------------------------------------------------------------------------------
 Females (13-50 years old)                            0.0007 1.4          4.3         0.15           21
----------------------------------------------------------------------------------------------------------------

     Mesotrione is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern.
     3. Aggregate cancer risk for U.S. population. Based on the lack of
carcinogenic response in rats and mice and the lack of mutagenic
effects, and that there are no data in the literature or SAR
information to indicate carcinogenic potential, no cancer risk is
posed.
     4. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to mesotrione residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology (high pressure liquid
chromatography) is available to enforce the tolerance expression. The
method may be requested from: Calvin Furlow, PIRIB, IRSD (7502C),
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW, Washington, DC 20460; telephone number: (703)
305-5229; e-mail address: furlow.calvin@epa.gov.

B. International Residue Limits

    There are no CODEX, Canadian, or Mexican tolerances/Maximum Residue
Levels for mesotrione residues. Thus, harmonization is not an issue at
this time.

C. Conditions

    Conversion of the mesotrione registration to unconditional under
section 3(c)(5) of Federal Insecticide and Fungicide Act (FIFRA) as
amended may be considered upon submission of adequate storage stability
data in the plant and livestock metabolism studies, revised
interference study, developmental neurotoxicity study (DNT) in the
mouse, and an 8 day inhalation study.

V. Conclusion

    Therefore, the tolerance is established for residues of mesotrione,
2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione, in or on
the raw agricultural commodities field corn grain, field corn forage
and field corn stover at 0.01 ppm.

VI. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to "object" to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-301138 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before August
20, 2001.
    1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW.,
Washington, DC 20460. The Office of the Hearing Clerk is open from 8
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
    2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it "Tolerance Petition Fees."
    EPA is authorized to waive any fee requirement "when in the
judgement of
the Administrator such a waiver or refund is equitable and not contrary
to the purpose of this subsection." For additional information
regarding the waiver of these fees, you may contact James Tompkins by
phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov, or by
mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460.
    3. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-301138, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-docket@epa.gov. Please use an ASCII file
format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; 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; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).

VII. Regulatory Assessment Requirements

    This final rule establishes a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994);
or OMB review or any Agency action under Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997). This action does not
involve any technical standards that would require Agency consideration
of voluntary consensus standards pursuant to section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (NTTAA),
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under FFDCA section 408(d), such as the tolerance in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure "meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications." "Policies that have federalism
implications" is defined in the Executive Order to include regulations
that have "substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government." This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). For these same reasons, the Agency has
determined that this rule does not have any "tribal implications" as
described in Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000). Executive Order 13175, requires EPA to develop an accountable
process to ensure "meaningful and timely input by tribal officials in
the development of regulatory policies that have tribal implications."
"Policies that have tribal implications" is defined in the Executive
Order to include regulations that have "substantial direct effects on
one or more Indian tribes, on the relationship between the Federal
government and the Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes."
This rule will not have substantial direct effects on tribal
governments, on the relationship between the Federal government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal government and Indian tribes, as specified in
Executive Order 13175. Thus, Executive Order 13175 does not apply to
this rule."

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of this final rule in the Federal Register. This final
rule is not a "major rule" as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and record
keeping requirements.

    Dated: June 4, 2001.
Joseph Merenda,
Acting Director, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as
follows:

    Authority: 21 U.S.C. 321(q), 346(a) and 371.

    2. Part 180 is amended by adding Sec. 180.571 to read as follows:

Sec. 180.571   Mesotrione; tolerances for residues.

    (a) General. Tolerances are established for residues of the
herbicide mesotrione, 2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-
cyclohexanedione, in or on the following commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Corn, field, forage                                                 0.01
Corn, field, grain                                                  0.01
Corn, field, stover                                                 0.01
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 01-15614 Filed 6-20-01; 8:45 am]