[Federal Register Volume 68, Number 24 (Wednesday, February 5, 2003)]
[Rules and Regulations]
[Pages 5839-5847]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-2771]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2002-0344; FRL-7289-7]


Cyprodinil; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes tolerances for residues of 
cyprodinil in or on the bushberry subgroup, caneberry subgroup, 
juneberry, lingonberry, pistachio, salal and watercress. The 
Interregional Research Project Number 4 (IR-4) requested these 
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA) , as 
amended by the Food Quality Protection Act of 1996 (FQPA).

DATES: This regulation is effective February 5, 2003. Objections and 
requests for hearings, identified by docket ID number OPP-2002-0344, 
must be received on or before April 7, 2003.

ADDRESSES: Written objections and hearing requests may besubmitted 
electronically, by mail, or through hand delivery/courier. Follow the 
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION.

FOR FURTHER INFORMATION CONTACT: Hoyt Jamerson, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW.,Washington, DC 20460-0001; telephone 
number: (703) 308-9368; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
    [sbull] Crop production (NAICS Code 111)
    [sbull] Animal production (NAICS Code 112)
    [sbull] Food manufacturing (NAICS Code 311)
    [sbull] Pesticide manufacturing (NAICS Code 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be

[[Page 5840]]

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

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2002-0344. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180--00.html, a 
beta site currently under development. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of May 1, 2002 ( 67 FR 21671)(FRL-6833-4), 
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a, 
as amended by FQPA (Public Law 104-170), announcing the filing of 
pesticide petitions (PP 2E6359, 2E6365, 2E6377 and 2E6393) by IR-4, 681 
U.S. Highway 1 South, North Brunswick, NJ 08902-3390. That 
notice included a summary of the petitions prepared by Syngenta Crop 
Protection, Inc., the registrant. There were no comments received in 
response to the notice of filing.
    The petitions 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 the 
caneberry subgroup at 10.0 parts per million (ppm) (2E6393), watercress 
at 20 ppm (2E6365), pistachio at 0.07 ppm (2E6377) and the bushberry 
subgroup, lingonberry, juneberry, and salal, at 3.0 ppm (2E6359). IR-4 
subsequently revised the petition to propose the following tolerances 
for cyprodinil residues in or on the caneberry subgroup at 10.0 parts 
per million (ppm), watercress at 20 ppm, pistachio at 0.10 ppm and the 
bushberry subgroup, lingonberry, juneberry, and salal, at 3.0 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) of the FFDCA defines ``safe'' to mean that``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of the FFDCA 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 of the FFDCA 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) of the FFDCA, 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) of the FFDCA, for a tolerance for residues of cyprodinil on 
the caneberry subgroup at 10.0 parts per million (ppm), watercress at 
20 ppm, pistachio at 0.10 ppm and the bushberry subgroup, lingonberry, 
juneberry, and salal, at 3.0 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 cyprodinil are 
discussed in Table 1 of this unit as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effectlevel 
(LOAEL) from the toxicity studies reviewed.

[[Page 5841]]



            Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
          Guideline No.               Study Type            Results
------------------------------------------------------------------------
870.3100                          90-Day oral         NOAEL = 73.3/103
                                   toxicity mouse      (male/female (m/
                                                       f)) milligram/
                                                       kilogram/day (mg/
                                                       kg/day)
                                                      LOAEL = 257/349 (m/
                                                       f) mg/kg/day
                                                       based on
                                                       histopathological
                                                       changes in the
                                                       liver (m/f)
------------------------------------------------------------------------
870.3100                          90-Day oral          NOAEL = 3.14 (mg/
                                   toxicity rat        kg/day)
                                                      LOAEL = 19 mg/kg/
                                                       day based on
                                                       increasedtubular
                                                       kidney lesions in
                                                       males
------------------------------------------------------------------------
870.3150                          90-Day oral-        NOAEL = 210/232 (m/
                                   toxicity - dog      f) mg/kg/day
                                                      LOAEL = 560/581 mg/
                                                       kg/day based on
                                                       lowerbody-weight
                                                       gains and
                                                       decreased food
                                                       consumption
                                                       inboth sexes
------------------------------------------------------------------------
870.3200                          Carcinogenicity -   NOAEL = 16.1 mg/kg/
                                   mice                day
                                                      LOAEL = 212.4 mg/
                                                       kg/day based on a
                                                       dose-related
                                                       increase in the
                                                       incidence of
                                                       focal and
                                                       multifocal
                                                       hyperplasia of
                                                       the exocrine
                                                       pancreas in males
                                                      No evidence of
                                                       carcinogenicity
------------------------------------------------------------------------
870.3700                          Prenatal            Maternal NOAEL =
                                   developmental -     200 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
                                                       lowermean fetal
                                                       weights and
                                                       increased
                                                       incidence of
                                                       delayedossificati
                                                       on
------------------------------------------------------------------------
870.3700                          Prenatal            Maternal NOAEL =
                                   developmental -     150 mg/kg/day
                                   rabbit             LOAEL = 400 mg/kg/
                                                       day based on
                                                       decreasedbody-
                                                       weight gain
                                                      Developmental
                                                       NOAEL = 150 mg/kg/
                                                       day
                                                      LOAEL = 400 mg/kg/
                                                       day based on
                                                       slight increase
                                                       of litters
                                                       showing extra
                                                       (13th) ribs
------------------------------------------------------------------------
870.3800                          Reproduction and    Parental/Systemic
                                   fertility effects   NOAEL = 81 mg/kg/
                                   - rat               day
                                                      LOAEL = 326 mg/kg/
                                                       day based on
                                                       lowerbody-weights
                                                       in the F0 females
                                                       during the pre-
                                                       matingperiod.
                                                      Reproductive/
                                                       Developmental
                                                       NOAEL = 81mg/kg/
                                                       day
                                                      LOAEL = 326 mg/kg/
                                                       day based on
                                                       decreasedpup
                                                       weights (F1 and
                                                       F2)
------------------------------------------------------------------------
870.4100                          Chronic toxicity    NOAEL = 65.63/
                                   dogs                67.99 (m/f) mg/kg/
                                                       day
                                                      LOAEL = 449.25/
                                                       446.3 (m/f) mg/kg/
                                                       day based on
                                                       lower body-weight
                                                       gains and
                                                       decreased food
                                                       consumption and
                                                       food efficiency
------------------------------------------------------------------------
870.4300                          Chronic toxicity/   NOAEL = 2.7 mg/kg/
                                   Carcinogenicity(f   day
                                   eeding) - rat      LOAEL = 35.6 mg/kg/
                                                       day based on
                                                       degenerative
                                                       liver lesions
                                                       (spongiosis
                                                       hepatis) in males
                                                      No evidence of
                                                       carcinogenicity
------------------------------------------------------------------------
870.5265 and 870.5100             Gene Mutation       In a reverse gene
                                                       mutation assay
                                                       withSalmonella
                                                       typhimurium/
                                                       Escherichia coli,
                                                       cyprodinil was
                                                       negative up to
                                                       concentrations
                                                       (>=1,250 [mu]g/
                                                       plate +/-S9) that
                                                       produced
                                                       reproducible
                                                       cytotoxicity for
                                                       the majority of
                                                       strains. Compound
                                                       insolubility was
                                                       reported at >=313
                                                       [mu]g/plate.
------------------------------------------------------------------------
870.5300                          Gene Mutation       In a Chinese
                                                       hamster V79 cell
                                                       HGPRT forward
                                                       gene mutation
                                                       assay, cyprodinil
                                                       was negative up
                                                       to cytotoxic
                                                       concentrations
                                                       (>=96.0 [mu]g/mL
                                                       with S9) (>=24
                                                       [mu]g/mL without
                                                       S9).
------------------------------------------------------------------------
870.5375                          Cytogenetics/In     In an in vitro
                                   vitro Chromosomal   assay for
                                   Aberration          chromosome
                                                       aberrations in
                                                       Chinese hamster
                                                       ovary (CHO)
                                                       cells, cyprodinil
                                                       gave negative
                                                       results up
                                                       tocytotoxic
                                                       concentrations
                                                       (>=50 [mu]g/mL
                                                       without S9, 18-
                                                       or 42-hour cell
                                                       harvest or >=25
                                                       [mu]g/mL with S9,
                                                       18-hour cell
                                                       harvest) or to
                                                       the highest sub-
                                                       cytotoxic
                                                       concentration (50
                                                       [mu]g/mL with S9,
                                                       42-hour cell
                                                       harvest).
------------------------------------------------------------------------

[[Page 5842]]

 
870.5395                          Cytogenetics/In     In an in vivo bone
                                   vivo bone marrow    marrow
                                   micronucleus        micronucleus
                                                       assay, cyprodinil
                                                       was negative when
                                                       administered
                                                       orally (gavage)
                                                       at 5,000 mg/
                                                       kg(HDT) to both
                                                       sexes of Tif:MAGF
                                                       mice. No signs of
                                                       overt toxicity or
                                                       clear evidence of
                                                       cytotoxicity for
                                                       the target organ
                                                       were noted at any
                                                       dose or sacrifice
                                                       time.
------------------------------------------------------------------------
870.5550                          Unscheduled DNA     In an Unscheduled
                                   Synthesis           DNA
                                                       Synthesis(UDS)
                                                       assay in primary
                                                       rat hepatocytes,
                                                       cyprodinil was
                                                       negative up to a
                                                       cytotoxic
                                                       concentration
                                                       (80[mu]g/mL).
------------------------------------------------------------------------
870.7485                          Metabolism and      Single oral doses
                                   pharmacokinetics    (0.5 or 100 mg/kg
                                                       bw) of phenyl or
                                                       pyrimidyl-
                                                       radiolabelled
                                                       cyprodinil
                                                       (purity >=98%)
                                                       were administered
                                                       toTif:RAIf(SPF)
                                                       rats, with one
                                                       low-dose group
                                                       receiving
                                                       unlabelled
                                                       cyprodinil
                                                       (purity >=99%)
                                                       for 2 weeks prior
                                                       to treatment with
                                                       radiolabelled
                                                       compound.
                                                       Absorption was
                                                       very rapid
                                                       (tcmax= 0.3
                                                       hours) with rapid
                                                       clearance (tcmax/
                                                       2=1.2 hours). A
                                                       minimum of 75% of
                                                       the administered
                                                       dose was
                                                       absorbed.
                                                       Excretion was
                                                       rapid and almost
                                                       complete, with
                                                       urine as the
                                                       principle route
                                                       of excretion (48-
                                                       68%), and >90%of
                                                       the administered
                                                       dose detected in
                                                       the urine and
                                                       feces within 48
                                                       hours. Excretion,
                                                       distribution and
                                                       metabolite
                                                       profiles were
                                                       essentially
                                                       independent of
                                                       dose level,
                                                       pretreatment, and
                                                       type of label,
                                                       although there
                                                       were some
                                                       quantitative
                                                       differences sex-
                                                       dependent
                                                       qualitative
                                                       differences in
                                                       two urinary
                                                       metabolite
                                                       fractions.
------------------------------------------------------------------------
870.7485                          Metabolism and      Excreta (Group D1
                                   pharmacokinetics    and D2) and bile
                                                       (Group G1) from
                                                       radiolabelled
                                                       cyprodinil-
                                                       treated
                                                       Tif:RAIf(SPF)
                                                       rats were used to
                                                       characterize,
                                                       isolateand
                                                       identify
                                                       cyprodinil
                                                       metabolites.
                                                       Eleven
                                                       metabolites were
                                                       isolated from
                                                       urine, feces and
                                                       bile, and the
                                                       metabolic
                                                       pathways in the
                                                       rat were
                                                       proposed. All
                                                       urinary and
                                                       biliary
                                                       metabolites (with
                                                       the exception of
                                                       7U) were
                                                       conjugated with
                                                       glucuronic acid
                                                       or sulfonated,
                                                       and excreted.
                                                       Cyprodinil was
                                                       almostcompletely
                                                       metabolized by
                                                       hydroxylation of
                                                       the phenyl ring
                                                       (position 4) or
                                                       pyrimidine ring
                                                       (position 5),
                                                       followed by
                                                       conjugation. An
                                                       alternative
                                                       pathwayinvolved
                                                       oxidation of the
                                                       phenyl ring
                                                       followed by
                                                       glucuronic acid
                                                       conjugation. A
                                                       quantitative sex
                                                       difference was
                                                       observed with
                                                       respect to
                                                       sulfonation ofthe
                                                       major metabolite
                                                       that formed 6U.
                                                       The monosulfate
                                                       metabolite (1U)
                                                       was predominant
                                                       in females,
                                                       whereas equal
                                                       amounts of mono-
                                                       and disulfate
                                                       (6U) conjugates
                                                       were noted in
                                                       males. Most of
                                                       the significant
                                                       metabolites in
                                                       feces were
                                                       exocons of
                                                       biliary
                                                       metabolites (2U,
                                                       3U, 1G). These
                                                       were assumed to
                                                       be deconjugated
                                                       in the
                                                       intestines,
                                                       partially
                                                       reabsorbed into
                                                       the
                                                       generalcirculatio
                                                       n, 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 (SF) 
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 SF.
    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

[[Page 5843]]

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 (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for cyprodinil used for human risk assessment is shown in 
Table 2 of this unit:

      Table 2.--Summary of Toxicological Dose and Endpoints for cyprodinil 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 females 13-50years of    Developmental NOAEL =    FQPA SF = 1X             Developmental Toxicity
 age                                    150 mg/kg/day           aPAD = acute RfD / FQPA    rabbit
                                       UF = 100...............   SF = 1.5 mg/kg/day.     Developmental LOAEL =
                                       Acute RfD = 1.5 mg/kg/                             400 mg/kg/day based on
                                        day.                                              slight increase of
                                                                                          litters showing extra
                                                                                          ribs (13th).
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations        NOAEL= 2.7               FQPA SF = 1X             2-Year Chronic Toxicity/
                                       UF = 100...............  cPAD = chronic RfD /      Carcinogenicity- rat
                                       Chronic RfD = 0.03 mg/    FQPA SF = 0.03 mg/kg/   LOAEL = 35.6 mg/kg/day
                                        kg/day.                  day.                     based on degenerative
                                                                                          liver lesions
                                                                                          (spongiosis hepatis)
                                                                                          in males.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)              Classification: ``not likely to be carcinogenic tohumans''
----------------------------------------------------------------------------------------------------------------
* The reference to the FQPA SF refers to any additional SF retained due to concerns unique tothe FQPA.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.352) for the residues of cyprodinil, in or on a 
variety of raw agricultural commodities. 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 one day 
or single exposure. The Dietary Exposure Evaluation Model (DEEM[reg]) 
analysis evaluated the individual food consumption as reported by 
respondents in the USDA insert 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 acute exposure assessments: 100% crop treated (PCT) and tolerance-
level residues for cyprodinil on all treated crops. This assessment was 
a Tier I analysis. However, the only acute endpoint identified was for 
the population subgroup females 13-50 years old based on a slight 
increase of litters showing extra ribs (13th). No effects that could be 
attributed to a single exposure were observed (no end point was chosen) 
for any other population subgroup, including the general U.S. 
population; therefore, an acute dietary assessment for the general U.S. 
population or other subgroups was not conducted.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the Dietary Exposure Evaluation Model (DEEM[reg]) 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: 100% crop treated (PCT) and tolerance-level residues for 
cyprodinil on all treated crops. This assessment was a Tier I analysis.
    2. Dietary exposure from drinking water. 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 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.

[[Page 5844]]

    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 percent of reference dose or 
percent of population adjusted dose. 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 for acute exposures 
are estimated to be 32 parts per billion (ppb) for surface water and 
0.04 ppb for ground water. The EECs for chronic exposures are estimated 
to be 6 ppb for surface water and 0.04 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).
    Cyprodinil 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) of the FFDCA 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.In general. Section 408 of the FFDCA 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 MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. There is no evidence of 
increased susceptibility of rat or rabbit fetuses followingin utero 
exposure in the developmental studies with cyprodinil. There is no 
evidence of increased susceptibility of young rats in the reproduction 
study with cyprodinil.
    3. Conclusion. With the exception of missing 21/28-day dermal- 
toxicity and 28-day inhalation-toxicity studies in rats, there is a 
complete toxicity data base for cyprodinil and exposure data are 
complete or are estimated based on data that reasonably accounts for 
potential exposures. Since there are no residential uses for cyprodinil 
the only exposure route to infants and children is the oral route, for 
which the toxicity and exposure data base is complete. Therefore dermal 
and inhalation-toxicity studies, are not needed to assess risk to 
infants and children and EPA determined that the 10X safety factor to 
protect infants and children should be reduced to 1X.
    The FQPA 10X safety factor is removed because:
    [sbull] i. There are currently no registered or proposed 
residential(non-occupational) uses of cyprodinil.
    [sbull] ii. There was no evidence (qualitative or quantitative) of 
increased susceptibility in the developmental rat or rabbit study 
following in utero exposure or in the two-generation reproduction study 
following pre- or post-natal exposure.
    [sbull] iii. There was also no evidence of a neurodevelopmental 
effect in the rat or rabbit developmental toxicity studies or in the 
rat two-generation reproductive-toxicity study.
    [sbull] iv. There are no data deficiencies for pre- and/or post-
natal exposure and hence there are no residual uncertainties.
    [sbull] v. Food and drinking water exposure assessments will 
notunderestimate the potential exposure for all populations, including 
infants and children.

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 are used to calculate DWLOCs: 2 liter (L)/
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, EPA concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when considered along 
with other sources of exposure for which EPA has reliable data) would 
not result in unacceptable levels of aggregate human health risk at 
this time. Because EPA 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, EPA will reassess the potential impacts 
of residues of the pesticide in

[[Page 5845]]

drinking water as a part of the aggregate risk assessment process.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to 
cyprodinil will occupy <1% of the aPAD for the subpopulation females 
13-50 years old, the only population for whom an effect attributable to 
an acute exposure could be observed. In addition, there is potential 
for acute 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 aPAD, as shown in Table 3 of this unit:

                      Table 3.--Aggregate Risk Assessment for Acute Exposure to cyprodinil
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                 aPAD (mg/      % aPAD     Water EEC    Water EEC   Acute DWLOC
                                                     kg)         (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
Females 13-50 years old                                  1.5         <1.0           32         0.04       44,000
----------------------------------------------------------------------------------------------------------------

    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 7.4% of the cPAD for the U.S. 
population, 24% 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. 
Based the use pattern, chronic residential exposure to residues of 
cyprodinil is not expected. 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 Table 4 of this unit:

              Table 4.-- Aggregate Risk Assessment for Chronic (Non- Cancer) Exposure to cyprodinil
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD mg/kg/     % cPAD     Water EEC    Water EEC     Chronic
                                                     day         (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                         0.03          7.4            6         0.04          970
----------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old)                              0.03           24            6         0.04          230
----------------------------------------------------------------------------------------------------------------
 Children 1-6 years old                                 0.03           22            6         0.04          230
----------------------------------------------------------------------------------------------------------------
Children 7-12 years old                                 0.03          9.1            6         0.04          270
----------------------------------------------------------------------------------------------------------------
Females 13-50years old                                  0.03          5.3            6         0.04        1,000
----------------------------------------------------------------------------------------------------------------

    3. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure take 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.
    5. Aggregate cancer risk for U.S. population. Cyprodinil has been 
classified as ``not likely to be carcinogenic in humans'' based on the 
results of a carcinogenicity study in mice and the combined chronic 
toxicity and carcinogenicity study in rats. Therefore, cyprodinil is 
not expected to pose a cancer risk to humans.
    6. 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

    The results of Multiresidue Method testing of cyprodinil and its 
metabolite CGA-232449 have been forwarded to the Food and Drug 
Administration (FDA). Cyprodinil was tested according to the FDA 
Multiresidue protocols (Protocols C, D, and E), and acceptable 
recoveries were obtained for cyprodinil fortified in apples at 0.50 ppm 
using Protocol D. The petitioner is proposing the Method AG-631A as a 
tolerance enforcement method for residues of cyprodinil in/on the 
subject crops. This method, entitled ``Analytical Method for the 
Determination of Residues of CGA-219417 in Crops by High Performance 
Liquid Chromatography With Column Switching,'' is a reissue of Methods 
AG-631 and REM 141.01. The method includes confirmatory procedures 
using gas chromatography/nitrogen/phosphorus detector (GC/NPD). The 
method has successfully undergone radiovalidation using 14C-
labeled tomato samples and independent laboratory validation. In 
addition, the method has been the subject of acceptable Agency petition 
method validations on stone fruits and almond nutmeat and hulls.

B. International Residue Limits

    There are no Mexican, Canadian or Codex maximum residue limits 
established for cyprodinil in/on caneberries, bushberries, pistachios 
and watercress, and thus no compatibility issues to be reconciled.

C. Conditions

    The Agency is requiring as conditions for registration the 
following:An acceptable 21/28-day dermal-toxicity study in rats (GLN 
870.3200). A 28-day inhalation-toxicity study in rats (GLN 870.3465)

V. Conclusion

    Therefore, the tolerance is established for residues of cyprodinil 
on the caneberry subgroup at 10.0 ppm, watercress at 20 ppm, pistachio 
at 0.10 ppm and the bushberry subgroup, lingonberry, juneberry, and 
salal, at 3.0 ppm.

[[Page 5846]]

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, EPA will continue to use those procedures, with 
appropriate adjustments, until the necessary modifications can be made. 
The new section 408(g) of the FFDCA 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) 
of FFDCA, as was provided in the old sections 408 and 409 of the FFDCA. 
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 ID number -OPP-2002-0344 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 April 7, 
2003.
    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 (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm.104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. 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 
(703) 603-0061.
    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 [email protected], 
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-
0001.
    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 20460-0001.
    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.1. Mail your 
copies, identified by docket ID number OPP-2002-0344, 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-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit I.B.1. You may also send an electronic copy of 
your request via e-mail to: [email protected]. 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. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of the 
FFDCA 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). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). 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

[[Page 5847]]

tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of the FFDCA, 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 section 408(n)(4) of the FFDCA. 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: January 24, 2003.
Peter Caulkins,
Acting 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 is amended by adding alphabetically the 
following commodities to the table in paragraph (a)(1) to read as 
follows:


Sec.  180.532  Cyprodinil; tolerances forresidues.

    (a) * * *
    (1) * * *

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Bushberry subgroup 13B...............................                3.0
Caneberry subgroup 13A...............................                 10
                                * * * * *
Juneberry............................................                3.0
Lingonberry..........................................                3.0
Pistachio............................................               0.10
                                * * * * *
Salal................................................                3.0
Watercress...........................................                 20
------------------------------------------------------------------------

* * * * *
[FR Doc. 03-2771 Filed 2-4-03; 8:45 am]
BILLING CODE 6560-50-S