[Federal Register Volume 66, Number 75 (Wednesday, April 18, 2001)]
[Rules and Regulations]
[Pages 19879-19891]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-9596]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301117; FRL-6778-8]
RIN 2070-AB78


Hexythiazox; Pesticide Tolerances

AGENCY:  Environmental Protection Agency (EPA).

ACTION:  Final rule.

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

SUMMARY:  This regulation establishes tolerances for residues of the 
ovicide/miticide hexythiazox (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-
methyl-2-oxothiazolidine-3-carboxamide) and its metabolites containing 
the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (expressed as 
parent) in or on tree nuts (nutmeat), plums, fresh prunes, dried 
prunes, pistachios, peppermint (tops), spearmint (tops), and 
caneberries. Gowan Company and the Interregional Research Project No. 4 
(IR-4) requested this tolerance under the Federal Food, Drug, and 
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act 
(FQPA) of 1996.

DATES:  This regulation is effective April 18, 2001. Objections and 
requests for hearings, identified by docket control number OPP-301117, 
must be received by EPA on or before June 18, 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-301117 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:  By mail: William G. Sproat, Jr., 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703)-308-8587; and e-mail 
address: [email protected].

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/. A frequently updated electronic 
version of 40 CFR part 180 is available at http://www.access.gpo/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.
    2. In person. The Agency has established an official record for 
this action under docket control number OPP-301117. 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

    Hexythiazox is the active ingredient in Savey Ovicide/Miticide 50 
WP (EPA Reg. No. 10163-208). Permanent tolerances are established under 
40 CFR 180.448(a) for residues of hexythiazox and its metabolites 
containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety 
(expressed as parent) in/on apples at 0.50 parts per million (ppm), wet 
apple pommace at 0.80 ppm; hops at 2.0 ppm, and pears at 0.3 ppm; milk, 
fat, and meat by-products of cattle, goats, horses, sheep, and swine at 
0.02 ppm; almonds at 0.30 ppm and almond hulls at 10 ppm; and 
strawberries at 3.0 ppm. Tolerances with regional registrations are 
established for cotton gin by-products (California only) at 3.0 ppm and 
undelinted cotton seed (California only) at 0.20 ppm.
    In the Federal Register of July 31, 1996 (61 FR 39971) (FRL-5384-
6); April 30, 1997 (62 FR 23455) (FRL-5600-8); January 28, 1998 (63 FR 
4252) (FRL-5763-6); and December 28, 2000 (65 FR 82349) (FRL-6761-6), 
EPA issued notices pursuant to section 408 of the FFDCA, 21 U.S.C. 346a 
as amended by the FQPA of 1996 (Public Law 104-170) announcing the 
filing of pesticide petitions for tolerances by Gowan Company, P.O. Box 
5569, Yuma, AZ 85366-5569, and the Interregional Research Project 
Number 4 (IR-4), Technology Centre of New Jersey, 681 U.S. Highway #1 
South, North Brunswick, NJ, 08902-3390. These notices included 
summaries of the petitions prepared by Gowan Company, the registrant. 
There were no comments received in response to the notice of filings.
    The petition(s) requested that 40 CFR 180.448 be amended by 
establishing tolerances for residues of the insecticide

[[Page 19880]]

hexythiazox, in or on various food commodities as follows:
    1. IR-4 petition 0E6198 proposes the establishment of tolerances 
for mint at 2.0 ppm.
    2. IR-4 petition 0E6215 proposes the establishment of tolerances 
for the caneberry subgroup at 1.0 ppm.
    3. Gowan Company petition PP 6F4738 proposes the establishment of 
tolerances for stone fruits including plums at 1 ppm; prunes at 5 ppm; 
and all tree nuts at 0.2 ppm.
    The existing tolerance for almonds is being deleted since it is 
covered under the tree nut group tolerance.
    Hexythiazox is currently proposed for use on mint to control 
Twospotted spider mites; stone fruits (including plums) to control 
European red mites, Twospotted spider mites, McDaniel spider mite, 
Strawberry spider mites, Pacific spider mites, Pecan leaf scorch mites, 
and Willamette mites; Tree nuts and pistachios to control European red 
mites, Twospotted spider mites, McDaniel spider mites, Strawberry 
spider mites, Pacific spider mites, Pecan leaf scorch mites, and 
Willamette mites; and on caneberries to control Twospotted spider 
mites, McDaniel spider mite, Yellow spider mite and Pacific spider 
mites.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including all anticipated dietary exposures 
and all other exposures for which there is reliable information.'' This 
includes exposure through drinking water and in residential settings, 
but does not include occupational exposure. Section 408(b)(2)(C) 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate exposure to the pesticide 
chemical residue * * *''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 and a complete description of 
the risk assessment process, see the final rule on Bifenthrin Pesticide 
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2), for a tolerance for residues of hexythiazox on tree nut 
group at 0.30 ppm; plums at 0.10 ppm; fresh prunes at 0.10 ppm; dried 
prunes at 0.40 ppm; pistachio at 0.30 ppm; peppermint (tops) at 2.0 
ppm; spearmint (tops) at 2.0 ppm; and caneberry crop group subgroup at 
1.0 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 hexythiazox are 
discussed in the following Table 1 as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effect level 
(LOAEL) from the toxicity studies reviewed.

            Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
         Guideline No.              Study type            Results
------------------------------------------------------------------------
870.3100                        90-Day oral        NOAEL = 8.1/5.4
                                 toxicity rodents   milligram/kilogram/
                                                    day (mg/kg/day)
                                                    males/females
                                                   LOAEL = 58.6/38.1 mg/
                                                    kg/day, males/
                                                    females, based on
                                                    increased absolute
                                                    and relative liver
                                                    weights in both
                                                    sexes, increased
                                                    relative ovarian and
                                                    kidney weights, and
                                                    fatty degeneration
                                                    of the adrenal zona
                                                    fasciculata
------------------------------------------------------------------------
870.3700a                       Prenatal           Maternal NOAEL = 240
                                 developmental in   mg/kg/day
                                 rodents           LOAEL = 720 mg/kg/day
                                                    based on decreased
                                                    maternal body weight
                                                    gain, and decreased
                                                    food consumption
                                                   Developmental NOAEL =
                                                    240 mg/kg/day
                                                   LOAEL = 720 mg/kg/day
                                                    based on delayed
                                                    ossification
------------------------------------------------------------------------
870.3700b                       Prenatal           Maternal NOAEL 1080 mg/kg/
                                 nonrodents         day
                                                   LOAEL > 1,080 mg/kg/
                                                    day
                                                   Developmental NOAEL >
                                                    1.080 mg/kg/day
                                                   LOAEL > 1,080 mg/kg/
                                                    day
------------------------------------------------------------------------
870.3800                        Reproduction and   Parental/Systemic
                                 fertility          NOAEL = 29.73/34.77
                                 effects            mg/kg/day, males/
                                                    females
                                                   LOAEL = 180.67/207.67
                                                    mg/kg/day, males/
                                                    females, based on
                                                    decreased body
                                                    weight gain and
                                                    increased absolute
                                                    and relative liver,
                                                    kidney, and adrenal
                                                    weights
                                                   Reproductive NOAEL >
                                                    180.67/207.67 mg/kg/
                                                    day, males/females
                                                   LOAEL > 180.67/207.67
                                                    mg/kg/day, males/
                                                    females
                                                   Offspring NOAEL =
                                                    29.73/34.77 mg/kg/
                                                    day, males/females
                                                   LOAEL = 180.67/207.67
                                                    mg/kg/day, males/
                                                    females, based on
                                                    decreased pup weight
                                                    during lactation,
                                                    and delayed hair
                                                    growth and/or eye
                                                    opening
------------------------------------------------------------------------
870.4100b                       Chronic toxicity   NOAEL = 2.5 mg/kg/day
                                 dogs              LOAEL = 12.5 mg/kg/
                                                    day based on
                                                    increased absolute
                                                    and relative adrenal
                                                    weights and
                                                    associated adrenal
                                                    histopathology
------------------------------------------------------------------------

[[Page 19881]]

 
870.4300                        Chronic toxicity/  NOAEL = 23/29 mg/kg/
                                 Carcinogenicity    day, males/females
                                 rats              LOAEL =163/207 mg/kg/
                                                    day, males/females
                                                    based on decreased
                                                    body weight and body
                                                    weight gain and
                                                    increased absolute
                                                    and relative liver
                                                    weights in both
                                                    sexes
                                                   No evidence of
                                                    carcinogenicity
------------------------------------------------------------------------
870.4300                        Carcinogenicity    NOAEL = 41.6/51.2 mg/
                                 mice               kg/day, males/
                                                    females
                                                   LOAEL = 267/318 mg/kg/
                                                    day, males/females
                                                    based on decreased
                                                    male body weight and
                                                    body weight gain,
                                                    and increased
                                                    absolute and
                                                    relative liver
                                                    weights in both
                                                    sexes.
                                                   Evidence of
                                                    carcinogenicity
                                                    (causes liver tumors
                                                    in females)
------------------------------------------------------------------------
870.5100                        Gene mutation      The test was negative
                                                    up to the highest
                                                    dose tested (HDT)
                                                    (6,400 g/
                                                    plate +/-S9)
------------------------------------------------------------------------
870.5300                        Gene mutation      Independently
                                                    performed trials
                                                    were negative up to
                                                    precipitating doses
                                                    (60 g/mL)
                                                    and severely
                                                    cytotoxic
                                                    concentrations (200
                                                    g/mL -S9;
                                                    400 g/mL
                                                    +S9)
------------------------------------------------------------------------
870.5375                        Cytogenetics       The test was negative
                                                    up to precipitating
                                                    doses accompanied by
                                                    severe cytotoxicity
                                                    ( 167 g/mL
                                                    +/-S9)
------------------------------------------------------------------------
870.5395                        Cytogenetics       The results were
                                                    inconclusive because
                                                    a positive response,
                                                    which was within the
                                                    wide range of
                                                    historical
                                                    background data, was
                                                    recorded for female
                                                    mice at the mid-and
                                                    high-doses (500 and
                                                    1,000 mg/kg). The
                                                    assay should be
                                                    repeated to confirm
                                                    or refute the
                                                    equivocal results.
------------------------------------------------------------------------
870.5550                        Other effects      The test was negative
                                                    up to a lethal dose
                                                    (250 g/mL)
------------------------------------------------------------------------
870.7485                        Metabolism and      Absorption and
                                 pharmacokinetics   distribution of
                                                    dosed radioactivity
                                                    were rapid. The
                                                    radioactive material
                                                    was rapidly
                                                    eliminated in the
                                                    urine and feces; the
                                                    majority of the
                                                    radioactivity was
                                                    eliminated within 24
                                                    hours. There were no
                                                    observable
                                                    differences in the
                                                    total elimination of
                                                    NA-73 between male
                                                    and female rats. The
                                                    major route of
                                                    elimination in both
                                                    the male and female
                                                    rats was by fecal
                                                    excretion. The major
                                                    metabolite found, PT-
                                                    1-8 (cis), accounted
                                                    for 8-12% of the
                                                    administered
                                                    radioactivity in the
                                                    low dose groups.
                                                    Approximately 11-20%
                                                    and 65-69% of the
                                                    dosed radioactivity
                                                    was identified as
                                                    unchanged NA-73 in
                                                    the low-dose and
                                                    high-dose groups,
                                                    respectively. All
                                                    other metabolites
                                                    were present at low
                                                    concentrations (<
                                                    2%). There was no
                                                    apparent sex
                                                    difference in
                                                    metabolite
                                                    formation.
                                                    Significant levels
                                                    of NA-73 equivalent
                                                    14C-residues were
                                                    detected in the fat,
                                                    liver, and adrenals.
                                                    A sex-related
                                                    difference in the
                                                    residue levels of
                                                    all tissues was
                                                    observed, with
                                                    residues in female
                                                    tissues being two-
                                                    fold higher than
                                                    those found in male
                                                    tissues.
------------------------------------------------------------------------
870.7485                        Metabolism and     Total recovery of
                                 pharmacokinetics   radioactivity 72
                                                    hours after
                                                    treatment accounted
                                                    for 101.9-103% of
                                                    the dose. The
                                                    distribution of
                                                    radioactivity 72
                                                    hours after dosing
                                                    was as follows: (1)
                                                    30% (male and
                                                    female) was excreted
                                                    in the urine, (2)
                                                    60% (female) to 67%
                                                    (male) was excreted
                                                    in the feces, and
                                                    (3) about 4% (male)
                                                    to 10% (female) of
                                                    the administered
                                                    radioactivity
                                                    remained in the
                                                    tissues, with the
                                                    highest
                                                    concentration in the
                                                    fat (2.3 ppm, males;
                                                    5.4 ppm, females).
                                                    Significant sex
                                                    differences existed
                                                    for the
                                                    pharmacokinetics of
                                                    NA-73 in these rats,
                                                    with females
                                                    exhibiting slower
                                                    elimination rats and
                                                    higher tissue
                                                    residues (about
                                                    double) than males.
                                                    NA-73 was
                                                    metabolized to a
                                                    large number of
                                                    metabolites that
                                                    were excreted both
                                                    in the urine and
                                                    feces. Seven
                                                    metabolites were
                                                    structurally
                                                    identified in
                                                    addition to the
                                                    parent compound in
                                                    both excreta of both
                                                    sexes, with the
                                                    major fecal
                                                    metabolite, PT-1-8
                                                    (cis) accounting for
                                                    10% of the dosed
                                                    radioactivity. The
                                                    others were all
                                                    minor metabolites
                                                    accounting for less
                                                    than 1.4%. About 20%
                                                    of the dose was
                                                    excreted as
                                                    unchanged NA-73 (97%
                                                    of which was in the
                                                    feces). No
                                                    significant sex
                                                    difference was
                                                    apparent with
                                                    respect to
                                                    metabolite
                                                    formation.
------------------------------------------------------------------------
870.7600                        Dermal             The total percent of
                                 penetration        dose absorbed
                                                    averaged 2%, 1%, and
                                                    1.1% for cannulated
                                                    rats (10-hour
                                                    sacrifice) and 0.8%,
                                                    0.2%, and 0.2% for
                                                    non-cannulated rats
                                                    (1-hour sacrifice)
                                                    at the low, medium,
                                                    and high dose
                                                    levels,
                                                    respectively. The
                                                    amount of
                                                    radioactivity in the
                                                    blood, carcass,
                                                    urine and other
                                                    organs totaled < 2%
                                                    of the applied dose.
                                                    The results of this
                                                    study (2% dermal
                                                    absorption) can be
                                                    used for risk
                                                    assessment purposes.
------------------------------------------------------------------------


[[Page 19882]]

B. Toxicological Endpoints

    The dose at which NOAEL from the toxicology study identified as 
appropriate for use in risk assessment is used to estimate the 
toxicological level of concern (LOC). However, the lowest dose at which 
adverse effects of concern are identified (the LOAEL) is sometimes used 
for risk assessment if no NOAEL was achieved in the toxicology study 
selected. An uncertainty factor (UF) is applied to reflect 
uncertainties inherent in the extrapolation from laboratory animal data 
to humans and in the variations in sensitivity among members of the 
human population as well as other unknowns. An UF of 100 is routinely 
used, 10X to account for interspecies differences and 10X for intra 
species differences. Discuss any additional UF (other than the FQPA SF) 
used in the assessment.
    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 in 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 hexythiazox used for human risk assessment is shown in 
the following Table 2:

     Table 2.--Summary of Toxicological Dose and Endpoints for Hexythiazox for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 FQPA SF* and level of
          Exposure scenario               Dose used in risk         concern for risk     Study and toxicological
                                            assessment, UF             assessment                effects
----------------------------------------------------------------------------------------------------------------
Acute dietary females 13-50 years of   NOAEL = 240 mg/kg/day    FQPA SF = 1X             Developmental toxicity
 age                                   UF = 100...............  aPAD = acute RfD.......  Study - Rat
                                       Acute RfD = 2.4 mg/kg/   FQPA SF = 2.4 mg/kg/day  Developmental LOAEL =
                                        day.                                              720 mg/kg/day based on
                                                                                          delayed ossification.
----------------------------------------------------------------------------------------------------------------
Acute dietary general population       A dose and endpoint
 including infants and children         attributable to a
                                        single exposure were
                                        not identified from
                                        the available oral
                                        toxicity studies,
                                        including maternal
                                        toxicity in the
                                        developmental toxicity
                                        studies.
----------------------------------------------------------------------------------------------------------------
Chronic dietary all populations        NOAEL= 2.5 mg/kg/day     FQPA SF = 1X             One year toxicity
                                       UF = 100...............  cPAD = chronic RfD.....   feeding
                                       Chronic RfD = 0.025mg/   FQPA SF = 0.025 mg/kg/   Study - Dog
                                        kg/day.                  day.                    LOAEL = 12.5 mg/kg/day
                                                                                          based on increased
                                                                                          absolute and relative
                                                                                          adrenal weights and
                                                                                          associated adrenal
                                                                                          histopathology.
----------------------------------------------------------------------------------------------------------------
Short-term dermal (1 to 7 days)        Oral maternal            LOC for MOE = 100        Developmental toxicity
(Occupational).......................  NOAEL= 240 mg/kg/day      (Occupational)          Study - Rat
                                        (dermal absorption                               LOAEL = 720 mg/kg/day
                                        rate = 2 %).                                      based on decreased
                                                                                          maternal body weight
                                                                                          gain during gestation
                                                                                          days 7-17 and
                                                                                          decreased food
                                                                                          consumption on
                                                                                          gestation days 9-12
----------------------------------------------------------------------------------------------------------------
Intermediate-term dermal (1 week -     Oral NOAEL= 5.4 mg/kg/   LOC for MOE = 100        13-Week feeding Study -
 several months)                        day (dermal absorption   (Occupational)           Rat
(Occupational).......................   rate = 2%)                                       LOAEL = 38.1 mg/kg/day
                                                                                          based on increased
                                                                                          absolute and relative
                                                                                          liver weights in both
                                                                                          sexes, increased
                                                                                          relative ovarian and
                                                                                          kidney weights, and
                                                                                          fatty degeneration of
                                                                                          the adrenal zone
                                                                                          fasciculata.
----------------------------------------------------------------------------------------------------------------
Short-term inhalation (1-7 days)       Oral NOAEL= 240 mg/kg/   LOC for MOE = 100        Developmental Toxicity
 (Occupational)                         day (inhalation          (Occupational)           Study - Rat
                                        absorption rate =                                LOAEL = 720 mg/kg/day
                                        100%)                                             based on decreased
                                                                                          maternal body weight
                                                                                          gain during gestation
                                                                                          days 7-17 and
                                                                                          decreased food
                                                                                          consumption on
                                                                                          gestation days 9-12.
----------------------------------------------------------------------------------------------------------------

[[Page 19883]]

 
Intermediate-term inhalation (1 week - Oral NOAEL= 5.4 mg/kg/   LOC for MOE = 100        13-Week Feeding Study -
  several months) (Occupational)        day (inhalation          (Occupational)           Rat
                                        absorption rate =                                LOAEL = 38.1 mg/kg/day
                                        100%)                                             based on increased
                                                                                          absolute and relative
                                                                                          liver weights in both
                                                                                          sexes, increased
                                                                                          relative ovarian and
                                                                                          kidney weights, and
                                                                                          fatty degeneration of
                                                                                          the adrenal zone
                                                                                          fasciculata.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      Category C (possible      Q1* =2.22 x 10-2        Increases in incidence
                                        human carcinogen)                                 of malignant and
                                                                                          combined benign/
                                                                                          malignant liver tumors
                                                                                          in mice.
----------------------------------------------------------------------------------------------------------------
*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 180.448) for the residues of hexythiazox, in or on 
a variety of raw agricultural commodities (RAC). Tolerances are 
established on plant commodities ranging from 0.02 ppm on apples to 3.0 
ppm on strawberries. Hexythiazox is the common name for the active 
ingredient in Savey Ovicide/Miticide. When formulated as the product 
Savey 50 WP, the product is registered for agricultural use on outdoor 
terrestrial food crops. When sold under an alternate brand name, 
Hexygon, the product is also registered for commercial non-food use on 
ornamental and nursery stock. Savey 50 WP contains 50% hexythiazox by 
weight. For these petitions, Savey\TM\ will be applied to caneberries, 
pistachios, tree nuts and stone fruits at a maximum of 0.188 pounds 
a.i./acre and to mint at a maximum of 0.156 pounds a.i./acre. Savey\TM\ 
is formulated as a wettable powder (packaged in open bags or water 
soluble paks) and is applied once per season or crop. Savey provides 
control against tetranychid mite species by direct or indirect contact 
with treated plant surfaces. According to label specifications the use 
of this product may include alternation of active classes of 
insecticides on succeeding generations and targeting the most 
susceptible life stage. Risk assessments were conducted by EPA to 
assess dietary exposures from hexythiazox 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 1-day or 
single exposure. The Dietary Exposure Evaluation Model (DEEM\TM\) 
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 acute 
exposure assessments: For acute dietary risk assessments, the entire 
distribution of single day food consumption events is combined with a 
single residue level (deterministic analysis) to obtain a distribution 
of exposure in mg/kg.
    A conservative analysis was performed using existing and EPA-
recommended tolerance level residues, DEEM\TM\ default processing 
factors, and 100% crop treated information for all commodities. For 
acute dietary risk, EPA's level of concern is < 100% aPAD. The acute 
dietary exposure estimate for the females 13-50 years old subgroup is 
presented in Table 3 at the 95\th\ percentile. The results of the acute 
analysis indicate that the estimated acute dietary risk for females 13-
50 years old associated with the existing and EPA-recommended uses of 
hexythiazox is below EPA's level of concern.

    Table 3.--Acute Result at  95th Percentitle from DEEMTM Analysis
------------------------------------------------------------------------
                                   Exposure  (mg/kg/
            Subgroup                     day)               % aPAD
------------------------------------------------------------------------
Females 13-50 years old           0.002619            < 1
------------------------------------------------------------------------

    EPA notes that there is a degree of uncertainty in extrapolating 
exposures for certain population subgroups which may not be 
sufficiently represented in the consumption surveys, (e.g., nursing 
infants). Therefore, risks estimated for these subpopulations were 
included in representative populations having sufficient numbers of 
survey respondents (e.g., all infants or females, 13-50 years old). 
Thus, the population subgroups listed in Tables 5 and 6 include those 
subgroups having sufficient numbers of survey respondents in the CSFII 
food consumption survey to be considered statistically reliable.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the DEEM\TM\ analysis evaluated the individual food 
consumption as reported by respondents in the USDA 1989-1992 nationwide 
CSFII and accumulated exposure to the chemical for each commodity. The 
following assumptions were made for the chronic exposure assessments: 
For chronic dietary risk assessments for residues in food, the 3-day 
average of consumption for each sub-population is combined with 
residues in commodities to determine average exposure in mg/kg/day. A 
partially refined chronic analysis was performed using anticipated 
residue (AR) levels, processing factors (where applicable), and percent 
crop treated (PCT) information. For chronic dietary risk, EPA's level 
of concern is > 100% cPAD. Dietary exposure estimates for the U.S. 
population and other representative subgroups are presented in Table 4. 
The results of the chronic analysis indicate that the estimated chronic 
dietary risk associated with the existing and EPA-recommended uses of 
hexythiazox is below EPA's level of concern for the U.S. population and 
all population subgroups.

       Table 4.--Summary of Results from Chronic DEEM\TM\ Analysis
------------------------------------------------------------------------
                                   Exposure (mg/kg/
            Subgroups                    day)               % cPAD
------------------------------------------------------------------------
U.S. population                   0.000011            < 1
------------------------------------------------------------------------
All infants (< 1 year old)        0.000034            < 1
------------------------------------------------------------------------

[[Page 19884]]

 
Children (1-6 years old)          0.000029            < 1
------------------------------------------------------------------------
Children (7-12 years old)         0.000016            < 1
------------------------------------------------------------------------
Females (13-50 years old)         0.000008            < 1
------------------------------------------------------------------------
Males (13-19 years old)           0.000004            < 1
------------------------------------------------------------------------
Males (20+ years old)             0.000008            < 1
------------------------------------------------------------------------
Seniors (55+ years old)           0.000010            < 1
------------------------------------------------------------------------

    iii. Cancer. A partially refined carcinogenic risk estimate 
analysis was performed using AR levels, processing factors (where 
applicable), and PCT information. The dietary exposure estimate from 
residues in food for the U.S. population is presented in Table 5. The 
result of the carcinogenicity analysis indicates that the estimated 
dietary risk from residues in food associated with the existing 
recommended uses is below the level the Agency generally considers 
negligible for excess lifetime cancer risk (the range of 10-
6).

    Table 5.--Summary of Results from Carcinogenic DEEM\TM\ Analysis
------------------------------------------------------------------------
                                   Exposure (mg/kg/
            Subgroup                     day)            Lifetime Risk
------------------------------------------------------------------------
U.S. population                   0.000011            2.54 x 10-\7\
------------------------------------------------------------------------

    For the chronic and cancer analyses, ARs from field trial data, the 
weighted average of PCT Quantitative Usage Analyses (QUA), and 
processing factors (where applicable) were used (see Table 6). DEEM 
processing factors were used unless otherwise noted in Table 6.

  Table 6.--Summary of Hexythiazox ARs for Chronic and Cancer Dietary Risk Assessment Based on Field-Trial Data
----------------------------------------------------------------------------------------------------------------
                                    Established or                                              CT/anticipated
          Commodity\a\                recommended      Processing factor       AR (ppm)          market share
                                   tolerances (ppm)           \b\                                   (%)\c\
----------------------------------------------------------------------------------------------------------------
Almond hulls                      10                  NA                  2.7                 2
----------------------------------------------------------------------------------------------------------------
Almond nutmeat                    0.30                NA                  0.046               2
----------------------------------------------------------------------------------------------------------------
Apples                            0.50                NA                  0.12                4
----------------------------------------------------------------------------------------------------------------
Apple juice                       0.50                0.5x                0.12                4
----------------------------------------------------------------------------------------------------------------
Apricots                          1.0                 NA                  0.20                2
----------------------------------------------------------------------------------------------------------------
Caneberry crop subgroup           1.0                 NA                  0.34                15
----------------------------------------------------------------------------------------------------------------
Cherries                          1.0                 NA                  0.20                <1
----------------------------------------------------------------------------------------------------------------
Cottonseed meal                   0.20                0.01x               0.059               1
----------------------------------------------------------------------------------------------------------------
Dates                             0.10                NA                  0.10                45
----------------------------------------------------------------------------------------------------------------
Fat\d\                            0.02                NA                  0.0000076
----------------------------------------------------------------------------------------------------------------
Hog fat                           0.02                NA                  6.3 x 10\-10\e
----------------------------------------------------------------------------------------------------------------
Hog liver                         0.02                NA                  4.8 x 10\-9e\
----------------------------------------------------------------------------------------------------------------
Hog meat by-products (except      0.02                NA                  2.0 x 10\-9e\
 liver)
----------------------------------------------------------------------------------------------------------------
Hops                              2.0                 NA                  2.0                 45
----------------------------------------------------------------------------------------------------------------
Liver\d\                          0.02                NA                  0.000058
----------------------------------------------------------------------------------------------------------------
Meat by-products (except          0.02                NA                  0.000024
 liver)\d\
----------------------------------------------------------------------------------------------------------------
Milk                              0.02                NA                  0.000 0053
----------------------------------------------------------------------------------------------------------------
Nectarines                        1.0                 NA                  0.054               2
----------------------------------------------------------------------------------------------------------------
Other nutmeat                     0.30                NA                  0.046               <1
----------------------------------------------------------------------------------------------------------------

[[Page 19885]]

 
Peaches                           1.0                 NA                  0.14                1
----------------------------------------------------------------------------------------------------------------
Pears                             0.30                NA                  0.30                3
----------------------------------------------------------------------------------------------------------------
Pecans                            0.30                NA                  0.01                <1
----------------------------------------------------------------------------------------------------------------
Peppermint, tops                  2.0                 0.23x               0.77                5
----------------------------------------------------------------------------------------------------------------
Plum                              0.10                NA                  0.050               <1
----------------------------------------------------------------------------------------------------------------
Plum, prune, dried                0.40                4.9 x               0.050               <1
----------------------------------------------------------------------------------------------------------------
Plum, prune, fresh                0.10                NA                  0.050               <1
----------------------------------------------------------------------------------------------------------------
Refined cottonseed oil            0.20                0.13x               0.059               1
----------------------------------------------------------------------------------------------------------------
Spearmint, tops                   2.0                 0.23x               0.77                5
----------------------------------------------------------------------------------------------------------------
Strawberries                      3.0                 NA                  0.75                14
----------------------------------------------------------------------------------------------------------------
Undelinted cottonseed             0.20                NA                  0.059               1
----------------------------------------------------------------------------------------------------------------
Wet apple pomace                  0.80                2.4 x               0.12                4
----------------------------------------------------------------------------------------------------------------
a ARs were not calculated for commodities not included in the current petitions.
b DEEM\TM\ default value used unless otherwise stated; DEEM\TM\ default ratio kept constant for ``apple-juice/
  cider'' and ``apple-juice-concentrate''.
c Electronic correspondence.
d These ARs were used for fat and meat byproducts of cattle, goats, horses, and sheep in the chronic and cancer
  analyses.
e These ARs were rounded up to 0.000001 ppm because DEEM\TM\ cannot accommodate more than 6 place holders.

    iv. Anticipated residue and PCT information. Section 408(b)(2)(E) 
authorizes EPA to use available data and information on the anticipated 
residue levels of pesticide residues in food and the actual levels of 
pesticide chemicals that have been measured in food. If EPA relies on 
such information, EPA must require that data be provided 5 years after 
the tolerance is established, modified, or left in effect, 
demonstrating that the levels in food are not above the levels 
anticipated. Following the initial data submission, EPA is authorized 
to require similar data on a time frame it deems appropriate. As 
required by section 408(b)(2)(E), EPA will issue a Data Call-In for 
information relating to anticipated residues to be submitted no later 
than 5 years from the date of issuance of this tolerance.
    Section 408(b)(2)(F) states that the Agency may use data on the 
actual percent of food treated for assessing chronic dietary risk only 
if the Agency can make the following findings: Condition 1, that the 
data used are reliable and provide a valid basis to show what 
percentage of the food derived from such crop is likely to contain such 
pesticide residue; Condition 2, that the exposure estimate does not 
underestimate exposure for any significant subpopulation group; and 
Condition 3, if data are available on pesticide use and food 
consumption in a particular area, the exposure estimate does not 
understate exposure for the population in such area. In addition, the 
Agency must provide for periodic evaluation of any estimates used. To 
provide for the periodic evaluation of the estimate of PCT as required 
by section 408(b)(2)(F), EPA may require registrants to submit data on 
PCT.
    The Agency used PCT information specified above. The Agency 
believes that the three conditions listed above have been met. With 
respect to Condition 1, PCT estimates are derived from Federal and 
private market survey data, which are reliable and have a valid basis. 
EPA uses a weighted average PCT for chronic dietary exposure estimates. 
This weighted average PCT figure is derived by averaging State-level 
data for a period of up to 10 years, and weighting for the more robust 
and recent data. A weighted average of the PCT reasonably represents a 
person's dietary exposure over a lifetime, and is unlikely to 
underestimate exposure to an individual because of the fact that 
pesticide use patterns (both regionally and nationally) tend to change 
continuously over time, such that an individual is unlikely to be 
exposed to more than the average PCT over a lifetime. The Agency is 
reasonably certain that the percentage of the food treated is not 
likely to be an underestimation. As to Conditions 2 and 3, regional 
consumption information and consumption information for significant 
subpopulations is taken into account through EPA's computer-based model 
for evaluating the exposure of significant subpopulations including 
several regional groups. Use of this consumption information in EPA's 
risk assessment process ensures that EPA's exposure estimate does not 
understate exposure for any significant subpopulation group and allows 
the Agency to be reasonably certain that no regional population is 
exposed to residue levels higher than those estimated by the Agency. 
Other than the data available through national food consumption 
surveys, EPA does not have available information on the regional 
consumption of food to which hexythiazox may be applied in a particular 
area.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for hexythiazox in drinking 
water. Because the Agency does not have comprehensive monitoring data,

[[Page 19886]]

drinking water concentration estimates are made by reliance on 
simulation or modeling taking into account data on the physical 
characteristics of hexythiazox.
    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 hexythiazox they are further 
discussed in the aggregate risk sections below.
    Based on the GENEEC and SCI-GROW models the EECs of hexythiazox for 
acute exposures are estimated to be 1.81 parts per billion (ppb) for 
surface water and 0.009 ppb for ground water. The EECs for chronic 
exposures are estimated to be 0.91 ppb for surface water and 0.009 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). Hexythiazox 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 hexythiazox 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, 
hexythiazox 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 hexythiazox 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 an UF (safety) in calculating a dose level that poses no 
appreciable risk to humans.
    ii. Prenatal and postnatal sensitivity. The prenatal and postnatal 
toxicology data base for hexythiazox is complete with respect to FQPA 
considerations. The results of these studies indicated no increased 
susceptibility of rats or rabbits to in utero and/or postnatal exposure 
to hexythiazox. In the developmental toxicity study in rabbits, no 
developmental effects were seen at doses up to the limit dose. In the 
developmental toxicity study in rats, the developmental effects 
(delayed ossification) occurred at the same dose level (720 mg/kg/day) 
as the maternal effects (decreased maternal body weight gain and 
decreased food consumption). In the two generation reproduction study, 
the effects in the offspring (decreased pup body weight during 
lactation and delayed hair growth and/or eye opening) were observed 
only at treatment levels which resulted in evidence of parental 
toxicity (decreased body weight gain and increased absolute and 
relative liver, kidney, and adrenal weights).
    A developmental neurotoxicity (DNT) study is not required at this 
time. However, EPA has requested an evaluation to determine the 
relationship between the adrenal effects (increased adrenal weights 
and/or adrenal pathology) seen in four studies (90-day feeding study in 
rats, chronic/carcinogenicity rat, chronic dog, and 2-generation 
reproduction study in rats) and the need for a DNT. It appears that the 
effects are more endocrine-related (not developmental). The possibility 
of the effects being endocrine-related is also supported by reports of 
ovarian weight increases in several studies in rats. In addition, the 
results of the developmental toxicity studies in rats and rabbits and 
the 2-generation reproduction study do not support a DNT. No 
neuropathology or central nervous system (CNS) malformations were seen 
in the developmental toxicity studies. In the 2-generation reproduction 
study in rats, there were no findings in pups that were suggestive of 
changes in neurological development, although no functional assessment 
was performed. Additionally, there was no evidence of neurotoxicity in 
other studies.
    2. Conclusion. There is a complete toxicity data base for 
hexythiazox and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. EPA determined 
that the 10X safety factor to protect infants and children should be 
removed and reduced to 1X. The FQPA factor is removed because an 
additional safety factor is not needed to protect the safety of infants 
and children.

[[Page 19887]]

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 EPA to calculate DWLOCs: 2L/70 killogram (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, 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 drinking water as a part of the 
aggregate risk assessment process.
    1. Acute risk. Acute aggregate risk estimates are below EPA's level 
of concern. An acute conservative dietary exposure analysis for 
hexythiazox was performed using tolerance level residues, DEEM\TM\ 
default processing factors, and assuming 100% CT for all commodities. 
The acute analysis applied to females 13-50 years old. The acute 
dietary exposure estimates (food only) for this population subgroup was 
<1% of the aPAD. Thus, the acute dietary risk associated with the 
proposed uses of hexythiazox does not exceed EPA's level of concern 
(>100% aPAD). The surface and ground water EECs were used to compare 
against back-calculated DWLOCs for aggregate risk assessments. For the 
acute scenario, the DWLOCs are 72,000 ppb for females 13-50 years old. 
For ground and surface water, the EECs for hexythiazox are less than 
EPA's DWLOCs for hexythiazox in drinking water as a contribution to 
acute aggregate exposure (Table 7). Therefore, EPA concludes with 
reasonable certainty that residues of hexythiazox in drinking water do 
not contribute significantly to the acute aggregate human health risk 
at the present time, as shown in Table 7:

                                      Table 7.--Drinking Water levels of Comparison for Acute Aggregated Exposures
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                          Allowable drinking
  Scenario/population subgroup     aPAD,  mg/kg/day   Dietary  exposure,  water exposure\1\,      DWLOC,  ppb     Surface water, ppb   Ground water, ppb
                                                           mg/kg/day           mg/kg/day
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13-50 years old)         2.4                 0.002619            2.4                 72,000              1.8                 0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
1Allowable Drinking Water Exposure (mg/kg/day) = aPAD (mg/kg/day) - Dietary Exposure from DEEM (mg/kg/day)

    2. Chronic risk. Chronic (non-cancer) aggregate risk estimates are 
below EPA's level of concern. A partially refined, chronic dietary 
exposure analysis for residues in food was performed using AR levels 
for most crops, processing factors where applicable and PCT or 
anticipated market share information for all crops. The chronic 
analysis applied to the U.S. population and all population subgroups. 
The chronic (non-cancer) dietary exposure estimates (food only) for the 
general U.S. population and all population subgroups were < 1% of the 
cPAD. Thus, the chronic (non-cancer) dietary risk associated with the 
proposed uses of hexythiazox does not exceed EPA's level of concern 
(>100% cPAD). The surface and ground water EECs were used to compare 
against back-calculated DWLOCs for aggregate risk assessments. For the 
chronic (non-cancer) scenario, the DWLOCs are 870 ppb for the U.S. 
population, 870 ppb for females 13-50 years old, and 250 ppb for all 
infants (< 1 year old). For ground and surface water, the EECs for 
hexythiazox are less than EPA's DWLOCs for hexythiazox in drinking 
water as a contribution to chronic (non-cancer) aggregate exposure 
(Table 8). Therefore, EPA concludes with reasonable certainty that 
residues of hexythiazox in drinking water do not contribute 
significantly to the chronic (non-cancer) aggregate human health risk 
at the present time, as shown in the following Table 8:

                               Table 8.--Drinking Water Levels of Comparison for Chronic (Non-Cancer) Aggregate Exposures
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                               Allowable
                                                      Dietary  exposure,    drinking water                           Surface water    Ground water  EEC,
  Scenario/population subgroup     cPAD,  mg/kg/day        mg/kg/day       exposure,\1\  mg/      DWLOC,  ppb          EEC, ppb               ppb
                                                                                kg/day
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. population                   0.025               0.000011            0.025               870                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
All infants (< 1 year old)        0.025               0.000034            0.025               250                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1-6 years old)          0.025               0.000029            0.025               250                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 19888]]

 
Children (7-12 years old)         0.025               0.000016            0.025               250                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13-50 years old)         0.025               0.000008            0.025               870                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
Males (13-19 years old)           0.025               0.000004            0.025               870                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
Males (20+ years old)             0.025               0.000008            0.025               870                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
Seniors (55+ years old)           0.025               0.000010            0.025               870                 0.910               0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
1 Allowable Drinking Water Exposure (mg/kg/day) = cPAD (mg/kg/day) - Chronic Dietary Exposure from DEEM (mg/kg/day).

    3. Short-term risk. Short-term aggregate exposure takes into 
account residential exposure plus chronic exposure to food and water 
(considered to be a background exposure level). Hexythiazox 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. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account residential exposure plus chronic exposure to food 
and water considered to be a background exposure level. Hexythiazox 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. Chronic (cancer) 
aggregate risk estimates are below EPA's level of concern. A partially 
refined analysis was performed using AR levels for most crops, 
processing factors where applicable, and PCT or anticipated market 
share information for all crops. The chronic cancer analysis applied to 
the U.S. population. The carcinogenic risk estimate (food only) for the 
general U.S. population was 2.5 x 10-7. Thus, the estimated 
dietary cancer risk to the U.S. population associated with the existing 
and recommended uses is below the level the Agency generally considers 
negligible for excess lifetime cancer risk (in the range of 
10-7). The surface and ground water EECs were used to 
compare against back-calculated DWLOCs for aggregate risk assessments. 
For the carcinogenic risk scenario, the DWLOCs are 1.2 ppb for the U.S. 
population. For ground and surface water, the EECs for hexythiazox are 
less than EPA's DWLOCs for hexythiazox in drinking water as a 
contribution to carcinogenic aggregate exposure (Table 9). Therefore, 
EPA concludes with reasonable certainty that residues of hexythiazox in 
drinking water do not contribute significantly to the carcinogenic 
aggregate human health risk at the present time.

                                 Table 9.--Drinking Water Levels of Comparison for Chronic (Cancer) Aggregate Exposures
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                               Allowable
                                                      Dietary  exposure,    drinking water                           Surface water    Ground water  EEC,
  Scenario/population subgroup            Q1*              mg/kg/day      exposure1,  mg/kg/     DWLOC,  ppb2          EEC, ppb               ppb
                                                                                  day
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. population                   2.2 2 x 10-\2\      0.000011            0.000034            1.2                 0.91                0.009
--------------------------------------------------------------------------------------------------------------------------------------------------------
1Allowable Drinking Water Exposure (mg/kg/day)= negligible risk(1x10-\6\)/Q1* - (average food + residential exposure (ADD) (mg/kg/day)
2DWLOC cancer= chronic water exposure (mg/kg/day) x body weight (kg)/water consumption (L) x 10-\3\(mg/g)

    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 hexythiazox residues.

IV. Other Considerations

A. Metabolism in Plants and Animals

    1. Plants. Metabolism studies have been submitted and reviewed in 
conjunction with petitions for hexythiazox tolerances in/on apples, 
pears, grapes and citrus. The residues of concern in these crops are 
hexythiazox and its metabolites containing the (4-chlorophenyl)-4-
methyl-2-oxo-3-thiazolidine moiety as specified in 40 CFR 180.448.
    No further plant metabolism data are necessary to support the 
proposed uses on caneberries, mint, tree nuts, pistachios, and stone 
fruit. However, as metabolism data are only available for fruit, the 
nature of the residue is not understood in mint. Given the limited 
metabolism of hexythiazox observed in apple, pear, grape and citrus 
leaves and that mint is a minor use (with minimal dietary exposure), 
EPA concludes that the nature of the residue is understood in mint for 
the purposes of this petition only.
    2. Livestock. The Agency has previously concluded that the nature 
of the residues of hexythiazox in cattle and goats is adequately 
understood. The residues of concern in ruminants are hexythiazox and 
its metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety.
    As there are no poultry feed items currently associated with 
caneberries, mint, tree nuts, pistachios, or stone

[[Page 19889]]

fruit, issues pertaining to the nature of the residue in poultry are 
not germane to these petitions.

B. Analytical Enforcement Methodology

    The HPLC/UV analytical methods used for determining the combined 
residues of hexythiazox and its metabolites in caneberries, mint, tree 
nuts, pistachios, and stone fruit are adequate for data collection 
purposes. Adequate method validation data were submitted. These methods 
are based on Method AMR-985-87, which has been deemed acceptable as a 
tolerance enforcement method in conjunction with a petition for use on 
apples. The method has been validated for use on various crop 
commodities, and has been forwarded to the Food and Drug Administration 
(FDA) for inclusion in PAM II. This earlier method is considered 
sufficient to enforce the proposed permanent tolerances for residues 
in/on caneberries, mint, tree nuts, pistachios, and stone fruit. The 
PAM-II analytical enforcement method for residues of hexythiazox and 
its metabolites (AMR-985-87) is available to measure residues in meat, 
milk, poultry and eggs.
    The petitioner has submitted data describing the testing of 
hexythiazox through FDA Multiresidue Protocols C through E. This 
information has been forwarded to the FDA for inclusion in PAM I . In 
addition, hexythiazox and its metabolites have been tested according to 
the FDA Multiresidue Protocols C through E by BASF Corporation in 
conjunction with a petition for use on hops. The information pertaining 
to the testing of hexythiazox per se, which indicated that hexythiazox 
was not recovered from hops, has been forwarded to the FDA. 
Multiresidue method testing data for the major metabolites of 
hexythiazox were forwarded to FDA.

C. Magnitude of Residues

    An adequate number of residue field trials reflecting the proposed 
use rules were submitted to EPA to demonstrate that tolerances for the 
tree nut group at 0.30 ppm; plums at 0.10 ppm; fresh prunes at 0.10 
ppm; dried prunes at 0.40 ppm; pistachio at 0.30 ppm; peppermint (tops) 
at 2.0 ppm; spearmint (tops) at 2.0 ppm; and the caneberry group 
subgroup at 1.0 ppm will not be exceeded when hexythiazox products 
labeled for these uses are used as directed. For plums, EPA is 
requiring submission of additional crop field studies from three other 
plum growing areas of the United States as confirmatory data in support 
of the proposed tolerances. In addition, for mint, EPA is requiring 
submission of additional crop field studies from two other mint growing 
areas of the United States as confirmatory data in support of the 
proposed tolerances.

D. Rotational Crop Restrictions

    As caneberries, mint, tree nuts, pistachios, and plums are 
perennial crops, confined and field rotational crop studies are not 
required to support the subject petitions.

E. International Residue Limits

    The Codex Alimentarius Commission has established maximum residue 
limits (MRLs) for residues of hexythiazox per se in/on cherries and 
peaches at 1 mg/kg, and plums (including prunes) at 0.2 mg/kg; no codex 
MRLs are established for residues in/on caneberry and mint commodities. 
The Codex MRLs and U.S. tolerances are not compatible because the U.S. 
tolerance expression currently includes parent hexythiazox and its 
metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety. Neither Canadian nor Mexican MRLs have been 
established for residues of hexythiazox in the subject crops.

V. Conclusion

    Therefore, tolerances are established for residues of the ovicide/
miticide hexythiazox (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-
oxothiazolidine-3-carboxamide) and its metabolites containing the (4-
chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (expressed as 
parent) in or on the tree nut group at 0.30 ppm; plums at 0.10 ppm; 
fresh prunes at 0.10 ppm; dried prunes at 0.40 ppm; pistachio at 0.30 
ppm; peppermint (tops) at 2.0 ppm; spearmint (tops) at 2.0 ppm; and the 
caneberry crop subgroup at 1.0 ppm.
    Conditional registration for use of hexythiazox on these crops are 
being proposed to allow development and review of a 21-day dermal 
toxicity study (OPPTS Guideline No. 870.3200) (data gap); an acceptable 
in vivo mouse micronucleus assay (OPPTS Guideline No. 870.5375); three 
additional plum residue field trials; and two additional mint residue 
field trials. The registrant has agreed to submit the 21-day dermal 
toxicity study and the in vivo mouse micronucleus assay in their letter 
dated September 15, 2000.

VI. Objections and Hearing Requests

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

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket control number OPP-301117 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 June 18, 
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.

[[Page 19890]]

    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.
    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-301117, 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: [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. Regulatory Assessment Requirements

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

[[Page 19891]]

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: April 9, 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 180.448 is amended by revising the table in paragraph 
(a) to read as follows:


Sec. 180.448  Hexythiazox; tolerances for residues.

    (a) General. * * *

 
------------------------------------------------------------------------
                                                                   Parts
                           Commodity                               per
                                                                 million
------------------------------------------------------------------------
Almond, hulls                                                      10
Apple                                                            0.50
Apple, wet pomace                                                0.80
Caneberry crop subgroup                                           1.0
Cattle, fat                                                      0.02
Cattle, mbyp                                                     0.02
Fruit, stone, group (except plums                                 1.0
Goat, fat                                                        0.02
Goat, mbyp                                                       0.02
Hops                                                              2.0
Horse, fat                                                       0.02
Horse, mbyp                                                      0.02
Milk                                                             0.02
Nut, tree, group                                                 0.30
Pear                                                             0.30
Peppermint, tops                                                  2.0
Pistachio                                                        0.30
Plum                                                             0.10
Plum, prune, dried                                               0.40
Plum, prune, fresh                                               0.10
Sheep, fat                                                       0.02
Sheep, mbyp                                                      0.02
Spearmint, tops                                                   2.0
Strawberry                                                        3.0
Swine, fat                                                       0.02
Swine, mbyp                                                      0.02
 
------------------------------------------------------------------------

* * * * *
[FR Doc. 01-9596 Filed 4-17-01; 8:45 am]
BILLING CODE 6560-50-S