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cyprodinil (Vangard) Time-Limited Pesticide Tolerance 6/01

 
ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301120; FRL-6778-7]
RIN 2070-AB78


Cyprodinil; Time-Limited Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes time-limited tolerances for
residues of cyprodinil in or on strawberry, dry bulb onion, and green
onion. IR-4 requested these tolerances under the Federal Food, Drug,
and Cosmetic Act, as amended by the Food Quality Protection Act of
1996. These tolerances will expire on December 31, 2003.

DATES: This regulation is effective June 22, 2001. Objections and
requests for hearings, identified by docket control number OPP-301120,
must be received by EPA on or before August 21, 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 number OPP-301120 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt Jamerson, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 308-9368; and e-mail address:
jamerson.hoyt@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
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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 to 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.
    2. In person. The Agency has established an official record for
this action under docket control number OPP-301120. 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 June 21, 2000 (65 FR 38535) (FRL-6558-
9), 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) 8E5012 for tolerances by, IR-4,
North Brunswick, New Jersey 08902-3390. This notice included a summary
of the petition prepared by Novartis Crop Protection, Inc., the
registrant. There were no comments received in response to the notice
of filing.
    The petition requested that 40 CFR 180.532 be amended by
establishing tolerances for residues of the fungicide cyprodinil, 4-
cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine, in or on strawberry at
5.0 parts per million (ppm) and the bulb vegetable crop group at 5 ppm.
The petition was subsequently amended by IR-4 to propose time-limited
tolerances for residues of cyprodinil in or on strawberry at 5.0 ppm,
dry bulb onion at 0.60 ppm, and green onion at 4.0 ppm. These
tolerances will expire on December 31, 2003.
    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 tolerances for residues of cyprodinil on strawberry at
5.0 ppm, dry bulb onion at 0.6 ppm and green onion at 4.0 ppm. EPA's
assessment of exposures and risks associated with establishing the
tolerances 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 cyprodinil 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
------------------------------------------------------------------------
                                28-Day oral        NOAEL = 10 mg/kg/day
                                 toxicity
                                 (gavage) (rat)

                                                   LOAEL = 100 mg/kg/day
                                                    based on based on
                                                    increased liver
                                                    weights and
                                                    abnormalities in
                                                    liver morphology
------------------------------------------------------------------------
870.3150                        90-Day oral        NOAEL = 210 mg/kg/day
                                 toxicity (dog)     (males) and 232 mg/
                                                    kg/day (females)

                                                   LOAEL = 560 mg/kg/day
                                                    (males) and 581 mg/
                                                    kg/day (females)
                                                    based on lower body
                                                    weight gains and
                                                    decreased food
                                                    consumption in both
                                                    sexes
------------------------------------------------------------------------
870.3200                        28-Day dermal      NOAEL = 5 mg/kg/day
                                 toxicity (rat)     (females) and 125 mg/
                                                    kg/day (males)


                                                   LOAEL = 25 mg/kg/day
                                                    for females and
                                                    1,000 mg/kg/day for
                                                    males based on
                                                    alterations in
                                                    clinical signs
                                                    (piloerection)
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 3.14 mg/kg/
                                 toxicity (rat)     day

                                                   LOAEL = 19 mg/kg/day
                                                    based on increased
                                                    chronic tubular
                                                    kidney lesions in
                                                    males
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 73.3/103 mg/
                                 toxicity (mouse)   kg/day, males/
                                                    females

                                                   LOAEL = 257/349 mg/kg/
                                                    day, males/females
                                                    based on
                                                    histopathological
                                                    changes in the liver
------------------------------------------------------------------------
870.3700a                       Prenatal           Maternal NOAEL = 200
                                 developmental      mg/kg/day
                                 (rat)

                                                   LOAEL = 1,000 mg/kg/
                                                    day based on lower
                                                    body weight/body
                                                    weight gain and
                                                    reduced food
                                                    consumption

                                                   Developmental NOAEL =
                                                    200 mg/kg/day

                                                   LOAEL = 1,000 mg/kg/
                                                    day based on lower
                                                    mean fetal weights
                                                    and an increased
                                                    incidence of delayed
                                                    ossification
------------------------------------------------------------------------
870.3700b                       Prenatal           Maternal NOAEL = 150
                                 developmental      mg/kg/day
                                 (rabbit)

                                                   LOAEL = 400 mg/kg/day
                                                    based on decreased
                                                    body weight gain

                                                   Developmental NOAEL =
                                                    150 mg/kg/day LOAEL
                                                    = 400 mg/kg/day
                                                    based on a slight
                                                    increase of litters
                                                    showing extra (13th)
                                                    ribs.
------------------------------------------------------------------------
870.3800                        Reproduction and   Parental/Systemic
                                 fertility          NOAEL = 81 mg/kg/day
                                 effects (rat)

                                                   LOAEL = 326 mg/kg/day
                                                    based on based on
                                                    lower body weights
                                                    in F0 females during
                                                    the pre-mating
                                                    period

                                                   Reproductive NOAEL =
                                                    81 mg/kg/day

                                                   LOAEL = 326 mg/kg/day
                                                    based on decreased
                                                    pup weights (F1 and
                                                    F2.
------------------------------------------------------------------------
870.4300                        Chronic toxicity/  NOAEL = 2.7 mg/kg/day
                                 carcinogenicity
                                 (rat)

                                                   LOAEL = 35.6 mg/kg/
                                                    day based on
                                                    degenerative liver
                                                    lesions (spongiosis
                                                    hepatis) in males.
                                                    There was no
                                                    evidence of
                                                    carcinogenicity in
                                                    rat fed diets
                                                    containing 0, 0.177,
                                                    2.7, 35.6 or 73.6 mg/
                                                    kg/day (males); 0,
                                                    0.204, 3.22, 41.2 or
                                                    87.1 mg/kg/day
                                                    (females) for 24-
                                                    months. There was an
                                                    increase in mammary
                                                    fibroadenomas from
                                                    controls to high
                                                    dose, which was
                                                    considered to be non-
                                                    treatment related.
------------------------------------------------------------------------
870.4100b                       Chronic toxicity   NOAEL = 65.63 mg/kg/
                                 (dog)              day (males) and
                                                    67.99 mg/kg/day
                                                    (females)

                                                   LOAEL = 446.37 mg/kg/
                                                    day (females) and
                                                    449.25 mg/kg/day
                                                    (males) based on
                                                    lower body weight
                                                    gains and decreased
                                                    food consumption and
                                                    food efficacy.
------------------------------------------------------------------------
870.4200                        Carcinogenicity    NOAEL = 16.1 mg/kg/
                                 in mice            day (males).

                                                   LOAEL = 212.4 mg/kg/
                                                    day based on a dose-
                                                    related increase in
                                                    the incidence of
                                                    focal and
                                                    mutltifocal
                                                    hyperplasia of the
                                                    exocrine pancreas in
                                                    males. There was no
                                                    evidence of
                                                    carcinogenicity.
------------------------------------------------------------------------
870.5100                        Gene mutation/     Negative in bacterial
                                 bacteria           cells (S.
                                                    typhimurium and (E.
                                                    coli) and mammalian
                                                    cells (V79/HGPRT
                                                    assay)
------------------------------------------------------------------------
870.5300                        Gene mutation/     Negative with and
                                 Mammalian cell     without activation
------------------------------------------------------------------------
870.5375                        Chromosome         Negative; up to 25
                                 aberration         micrograms/milliter
                                 (Chinese hamster   (g/ml) (-
                                 ovary)             S9); up to 50 g/ml (+S9)
------------------------------------------------------------------------
870.5550                        In vitro           Negative; 0.74 to 80
                                 unscheduled DNA    g/ml;
                                 synthesis assay -  cytotoxicity was
                                  primary rat       seen at
                                 hepatocytes        concentrations of 80
                                                    g/ml
------------------------------------------------------------------------

870.5395                        In vivo mouse      Negative; single dose
                                 micronucleus       (gavage) 1,250 or
                                 assay - bone       5,000 mg/kg
                                 marrow
------------------------------------------------------------------------
870.7485                        Metabolism and     In a metabolism study
                                 pharmacokinetics   in rats, single oral
                                                    doses (0.5 or 100 mg/
                                                    kg bw) of phenyl or
                                                    pyrimidyl-
                                                    radiolabelled
                                                    cyprodinil were
                                                    administered, with
                                                    one low-dose group
                                                    receiving unlabeled
                                                    cyprodinil for 2
                                                    weeks prior to
                                                    treatment with
                                                    radiolabelled
                                                    compound. Excretion
                                                    was rapid and almost
                                                    complete, with urine
                                                    as the principle
                                                    route of excretion.
                                                    Tissue residues
                                                    declined rapidly,
                                                    with the highest
                                                    concentrations ( 1.8 ppm)
                                                    found in kidneys,
                                                    liver, lungs,
                                                    spleen, thyroid,
                                                    whole blood, and
                                                    carcass. Unchanged
                                                    parent compound was
                                                    detected in feces
                                                    extract only.
                                                    Excretion,
                                                    distribution and
                                                    metabolite profiles
                                                    were essentially
                                                    independent of dose
                                                    level, pretreatment,
                                                    and type of label,
                                                    although there were
                                                    some sex- dependent
                                                    qualitative
                                                    differences in two
                                                    urinary metabolite
                                                    fractions. Eleven
                                                    metabolites were
                                                    isolated from urine,
                                                    feces and bile, and
                                                    the metabolic
                                                    pathways in the rat
                                                    were proposed. All
                                                    urinary and biliary
                                                    metabolites (with
                                                    one exception) were
                                                    conjugated with
                                                    glucuronic acid or
                                                    sulfonated, and
                                                    excreted. Cyprodinil
                                                    was almost
                                                    completely
                                                    metabolized by
                                                    hydroxylation of the
                                                    phenyl ring
                                                    (position 4) or
                                                    pyrimidine ring
                                                    (position 5),
                                                    followed by
                                                    conjugation. An
                                                    alternative pathway
                                                    involved oxidation
                                                    of the phenyl ring
                                                    followed by
                                                    glucuronic acid
                                                    conjugation. A
                                                    quantitative sex
                                                    difference was
                                                    observed with
                                                    respect to
                                                    sulfonation of the
                                                    major metabolite.
                                                    The monosulfate
                                                    metabolite was
                                                    predominant in
                                                    females, whereas
                                                    equal amounts of
                                                    mono- and disulfate
                                                    conjugates were
                                                    noted in males. Most
                                                    of the significant
                                                    metabolites in feces
                                                    were exocons of
                                                    biliary metabolites.
                                                    These were assumed
                                                    to be deconjugated
                                                    in the intestines,
                                                    partially reabsorbed
                                                    into the general
                                                    circulation,
                                                    conjugated again,
                                                    and eliminated
                                                    renally. The major
                                                    metabolic pathways
                                                    of cyprodinil were
                                                    not significantly
                                                    influenced by the
                                                    dose, treatment
                                                    regimen, or sex of
                                                    the animal.
------------------------------------------------------------------------

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 intraspecies differences.
    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 cyprodinil used for human risk assessment is shown in the
following Table 2:

      Table 2.--Summary of Toxicological Dose and Endpoints for Cyprodonil for use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                          Dose Used in Risk      FQPA SF* and Endpoint   Study and Toxicological
          Exposure Scenario                 Assessment, UF        for Risk Assessment            Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (all populations)        Not applicable           Not applicable           There were no effects
that could be
attributed to a single
exposure (dose) in
oral toxicity studies
including the
developmental toxicity
studies in rats and
rabbits.
----------------------------------------------------------------------------------------------------------------

Chronic dietary (all populations)      NOAEL= 2.7 mg/kg/day     FQPA SF = 1              Combined/chronic
toxicity - rat

                                       UF = 100                 cPAD = 0.03  1   LOAEL = 35.6 mg/kg/day
                                                                 0.03 mg/kg/day           based on increased
incidence of
spongiosis hepatis in
the liver

                                       Chronic RfD = 0.03 mg/
                                        kg/day


----------------------------------------------------------------------------------------------------------------
Short-term dermal (1-7 days)           Dermal study NOAEL=      LOC for MOE = 100        21-day dermal study -
                                        25.0 mg/kg/day (includes the FQPA SF)   rat

LOAEL = 125 mg/kg/day
based on hunched
posture
----------------------------------------------------------------------------------------------------------------
Intermediate- term dermal (1 week -    Dermal study NOAEL=      LOC for MOE = 100        21-day dermal study -
 several months)                        25.0 mg/kg/day (includes the FQPA SF)   rat

LOAEL = 125 mg/kg/day
based on hunched
posture
----------------------------------------------------------------------------------------------------------------
Long-term dermal (several months -     Not applicable           Not applicable           Based on the current
 lifetime) use pattern, there is
no potential for long-
term dermal exposure.
----------------------------------------------------------------------------------------------------------------
Inhalation (any time period)           Not applicable           Not applicable           The current use
pattern, the low
exposure potential and
the low toxicity
(Toxicity Category
III) do not indicate a
significant potential
for exposure via this
route.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      ``Not likely'' to be a   Not applicable           There is no evidence of
                                        human carcinogen carcinogenic
potential, therefore,
cancer risk assessment
is not required.
----------------------------------------------------------------------------------------------------------------
* The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
  to the FQPA.

C. Exposure Assessment

     1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.532(a)) for the residues of cyprodinil, in or
on food commodities as follows: almond nutmeats at 0.02 ppm, almond
hulls at 0.05 ppm, pome fruit at 0.1 ppm, apple, wet pomace at 0.15
ppm, grapes at 2.0 ppm, raisins at 3.0 ppm and stone fruit at 2.0 ppm.
Time-limited tolerances in association with section 18 of FIFRA
(emergency exemptions) have been established under 180.532(b) for
caneberries at 10 ppm and strawberries at 5.0 ppm. Risk assessments
were conducted by EPA to assess dietary exposures from cyprodinil 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 1 day or
single exposure. The Agency did not conduct an acute dietary risk
assessment since no toxicological endpoint of concern was identified
during the review of the available data.
     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: A conservative analysis was performed using published and
proposed tolerance level residues and 100% crop treated information for
all commodities.
     iii. Cancer. Cyprodinil is classified as ``not likely'' to be a
human carcinogen by all routes of exposure based on lack of evidence of
carcinogenicity in mice and rats, therefore, a cancer risk assessment
was not performed.
    2. Dietary exposure from drinking water. Cyprodinil has a low
potential for significant movement into ground water under most
conditions. There is a moderate risk of cyprodinil contaminating
surface water as runoff and through erosion of soil particles to which
cyprodinil is absorbed. However, if cyprodinil residues were to reach
surface water and/or ground water, it may persist for a significant
period of time.
    The Agency lacks sufficient monitoring exposure data to complete a
comprehensive dietary exposure analysis and risk assessment for
cyprodinil 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 cyprodinil.
    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 ground water. 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 cyprodinil they are further
discussed in the aggregate risk sections below.
    Based on the PRZM/EXAMS and SCI-GROW models the estimated
environmental concentrations (EECs) of cyprodinil in surface water and
ground water for acute exposures are estimated to be 52.9 parts per
billion (ppb) for surface water and 0.033 ppb for ground water. The
EECs for chronic exposures are estimated to be 51 ppb for surface water
and 0.033 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).
    Cyprodonil 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 cyprodinil 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,
cyprodinil 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 cyprodinil 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 no indication of
quantitative or qualitative increased susceptibility of rats or rabbits
to in utero and/or postnatal exposure.
    2. Conclusion. EPA determined that the 10X safety factor to protect
infants and children should be removed. The FQPA factor is removed
because: The toxicology data base is complete for the assessment of the
effects following in utero and/or postnatal exposure; there is no
indication of quantitative or qualitative increased susceptibility of
rats or rabbits to in utero and/or postnatal exposure; EPA determined
that a developmental neurotoxicity study is not required; the dietary
(food and drinking water) exposure assessments will not underestimate
the potential exposures for infants and children; and there are no
registered residential uses at the current time.

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 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 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 ground water 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 aggregate risk is negligible since no acute
toxicological endpoint of concern was identified.
    2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
cyprodinil from food will utilize 7% of the cPAD for the U.S.
population, 23% of the cPAD for all infants < 1 year old and 22% of the
cPAD for children 1-6 years old. There are no residential uses for
cyprodinil that result in chronic residential exposure to cyprodinil.
In addition, there is potential for chronic dietary exposure to
cyprodinil in drinking water. After calculating DWLOCs and comparing
them to the EECs for surface and ground water, EPA does not expect the
aggregate exposure to exceed 100% of the cPAD, as shown in the
following Table 3:

               Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Cyprodinil
----------------------------------------------------------------------------------------------------------------
Ground
       Population Subgroup         cPAD (mg/kg)     % cPAD (Food) Surface Water EEC   Water EEC     Chronic
(ppb)           (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                             0.03                  7 51        0.033          974
----------------------------------------------------------------------------------------------------------------
Infant < 1 year old                         0.03                 23 51        0.033          230
----------------------------------------------------------------------------------------------------------------

    3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level).
    Cyprodinil 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.
    4. Aggregate cancer risk for U.S. population. Cyprodinil is
classified as ``not likely to be human carcinogen,'' therefore, EPA
concludes that cyprodinil poses no greater than a negligible cancer
risk.
    5. 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 cyprodinil residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Ciby Geigy Method AG-631A is adequate for enforcement of tolerances
for residues of cyprodinil in/on strawberry and dry bulb and green
onions. Method AG-631A is a reissue of Method(s) AG-631/REM 141.01
which has successfully undergone an independent laboratory validation
(ILV) as well as an Agency petition method validation (PMV) in
conjunction with permanent tolerance petitions for use on stone fruits
and almonds. The method includes a GC-NPD confirmatory method and has
been radiovalidated using samples of 14C cyprodinil-treated
tomatoes. Once minor deficiencies cited in the PMVs have been resolved
(the petitioner was required to submit a standard of cyprodinil and
material safety data sheet (MSDS) to the EPA repository and to
incorporate the necessary method revisions), the method will be
forwarded to FDA for inclusion in PAM II.
    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 maximum residue limits for
strawberries, dry bulb onions or green onions.

C. Conditions

    The residue field trials do not support permanent tolerances for
cyprodinil residues in or on strawberry and onions. The residue field
trials were conducted at exaggerated application rates (2.3 times the
proposed use rates). Since EPA expects that residues from field trials
preformed at the proposed use rates will be lower than those reported
at the 2.3 times rate, conditional registration and time-limited
tolerances may be established using the available data on strawberry
and onions.
    Based on the findings from a confined accumulation in rotational
crops study, EPA has concluded that a field accumulation in rotational
crop study should be conducted and residues of the cyprodinil
metabolites (CGA-249287, CGA-263208, CGA-232449 and NOA-422054) should
be monitored and reported to the Agency.
    Based on structural similarities to genotoxic nucleotide analogs,
there was concern that the pyrimidine metabolites (CGA-249287, NOA-
422054) may be more toxic than the parent compound. However, EPA's
review indicates similar results in an acute oral and mutagenicity
studies with both the parent compound and the CGA-249287 metabolite.
EPA concluded that the toxicity of the CGA-249287 and NOA-422054
metabolites is no greater than that of the parent, conditional on
submission and review of confirmatory data of an acute oral toxicity
study and bacterial reverse mutation assay for the NOA-422054
metabolite. Although the metabolites CGA-232449 and CGA-263208 were
determined to be of potential toxicological concern, they are not
expected to be more toxic than cyprodinil per se.
    Upon receipt and evaluation of additional residue field trials for
strawberries, dry bulb onions, and green onions; field accumulation in
rotational crops study for the CGA-249287, NOA-422054, CGA-263208, and
CGA-232449 metabolites; and formal submission and review of
confirmatory data from an acute oral toxicity study and Ames assay for
the CGA-249287 and NOA-422054 metabolites; the Agency will reassess
these tolerances and, if appropriate, will establish permanent
tolerances for strawberry, dry bulb onion and green onion. A rotational
crop restriction will be imposed, which will limit the plant-back to
crops which have established cyprodinil tolerances.

V. Conclusion

    Therefore, these tolerances are established for residues of
cyprodinil, 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine, in or on
strawberry at 5.0 ppm, dry bulb onion at 0.60 ppm, and green onion at
4.0 ppm. These tolerances will expire on December 31, 2003.

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

[[Page 33485]]

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-301120 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
21, 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-301120, 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 other 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
recordkeeping requirements.


    Dated: June 7, 2001.

James Jones,
Director, Registration Division, 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. Section 180.532(a) is amended by designating the text following
the paragraph heading as paragraph (a)(1) and adding paragraph (a)(2)
to read as follows:


Sec. 180.532  Cyprodinil; tolerances for residues.

    (a) *  *  *
    (2) Time-limited tolerances are established for residues of the
fungicide cyprodinil, 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine
in or on the following food commodities.

------------------------------------------------------------------------
                                                          Expiration/
            Commodity              Parts per million    revocation date
------------------------------------------------------------------------
Onion, dry bulb                   0.60                12/31/03
Onion, green                      4.0                 12/31/03
Strawberry                        5.0                 12/31/03
------------------------------------------------------------------------

* * * * *

[FR Doc. 01-15620 Filed 6-21-01 8:45 a.m.]