Document ID: EPA-HQ-OPP-2005-0518-0001
Agency: epa
Document Type: Proposed Rule
Title: Hexythiazox; Proposed Pesticide Tolerance
Posted Date: 2005-12-30T13:54:09Z

[Federal Register: December 30, 2005 (Volume 70, Number 250)]
[Proposed Rules]               
[Page 77363-77371]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30de05-22]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0518; FRL-7752-1]

 
Hexythiazox; Proposed Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: This document proposes to establish tolerances for combined 
residues of 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-

[[Page 77364]]

thiazolidine moiety (expressed as parent) in or on grape; citrus fruit, 
crop group 10 (CA, AZ, TX only); citrus, oil; citrus, dried pulp; 
fruit, pome, group 11; apple, wet pomace; and cattle, sheep, goat, and 
horse meat byproducts under the Federal Food, Drug, and Cosmetic Act 
(FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).

DATES: Comments must be received on or before January 30, 2006.

ADDRESSES: Submit your comments, identified by docket identification 
(ID) number EPA-HQ-OPP-2005-0518, by one of the following methods:
     Federal eRulemaking Portal http://www.regulations.gov/. 

Follow the on-line instructions for submitting comments.
     Agency Website: EDOCKET, EPA's electronic public docket 
and comment system was replaced on November 25, 2005, by an enhanced 
Federal-wide electronic docket management and comment system located at 
http://www.regulations.gov/. Follow the on-line instructions.

     E-mail: Comments may be sent by e-mail to 
opp-docket@epa.gov, Attention: Docket ID number EPA-HQ-OPP-2005-0518.

     Mail: Public Information and Records Integrity Branch 
(PIRIB) (7502C), Office of Pesticide Programs (OPP), Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001, Attention: Docket ID number EPA-HQ-OPP-2005-0518.
     Hand delivery: Public Information and Records Integrity 
Branch (PIRIB), Office of Pesticide Programs (OPP), Environmental 
Protection Agency, Rm. 119, Crystal Mall 2, 1801 S. Bell St., 
Arlington, VA, Attention: Docket ID number EPA-HQ-OPP-2005-0518. Such 
deliveries are only accepted during the Docket's normal hours of 
operation, and special arrangements should be made for deliveries of 
boxed information.
     Instructions: Direct your comments to docket ID number EPA-HQ-OPP-
2005-0518. EPA's policy is that all comments received will be included 
in the public docket without change and may be made available online at 
http://www.epa.gov/docket, including any personal information provided, 

unless the comment includes information claimed to be Confidential 
Business Information (CBI) or other information whose disclosure is 
restricted by statute. Do not submit information that you consider to 
be CBI or otherwise protected through EDOCKET, regulations.gov, or e-
mail. The EPA EDOCKET and the regulations.gov websites are ``anonymous 
access'' system, which means EPA will not know your identity or contact 
information unless you provide it in the body of your comment. If you 
send an e-mail comment directly to EPA without going through the 
EDOCKET and or regulations.gov; your e-mail address will be 
automatically captured and included as part of the comment that is 
placed in the public docket and made available on the Internet. If you 
submit an electronic comment, EPA recommends that you include your name 
and other contact information in the body of your comment and with any 
disk or CD ROM you submit. If EPA cannot read your comment due to 
technical difficulties and cannot contact you for clarification, EPA 
may not be able to consider your comment. Electronic files should avoid 
the use of special characters, any form of encryption, and be free of 
any defects or viruses. For additional information about EPA's public 
docket visit EDOCKET on line or see the Federal Register of May 31, 
2002 (67 FR 38102) (FRL-7181-7).
     Docket: All documents in the docket are listed in the 
http://www.regulations.gov index. Although listed in the index, some 

information is not publicly available, i.e., CBI or other information 
whose disclosure is restricted by statute. Certain other material, such 
as copyrighted material, will be publicly available only in hard copy 
form. Publicly available docket materials are available either 
electronically in http://www.regulations.gov or in hard copy at the Public 

Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 
2, 1801 S. Bell St., Arlington, VA. This Docket Facility is 
open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The Docket telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Olga Odiott, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-9369; e-mail address: odiott.olga@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111)
     Animal production (NAICS code 112)
     Food manufacturing (NAICS code 311)
     Pesticide manufacturing (NAICS code 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

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

    In addition to using EDOCKET (http://www.epa.gov/edocket/), you may 

access this Federal Register document electronically through the EPA 
Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/.
 A frequently updated electronic version of 40 CFR part 180 

is available on E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.

C. What Should I Consider as I Prepare My Comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through 
http://www.regulations.gov, or e-mail. Clearly mark the part or all of the 

information that you claim to be CBI. For CBI information in a disk or 
CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as 
CBI and then identify electronically within the disk or CD ROM the 
specific information that is claimed as CBI). In addition to one 
complete version of the comment that includes information claimed as 
CBI, a copy of the comment that does not contain the information 
claimed as CBI must be submitted for inclusion in the public docket. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When submitting comments, 
remember to:
    i. Identify the rulemaking by docket ID number and other 
identifying information (subject heading, Federal Register date, and 
page number).
    ii. Follow directions. The Agency may ask you to respond to 
specific questions or organize comments by referencing a

[[Page 77365]]

Code of Federal Regulations (CFR) part or section number.
    iii. Explain why you agree or disagree; suggest alternatives and 
substitute language for your requested changes.
    iv. Describe any assumptions and provide any technical information 
and/or data that you used.
    v. If you estimate potential costs or burdens, explain how you 
arrived at your estimate in sufficient detail to allow for it to be 
reproduced.
    vi. Provide specific examples to illustrate your concerns, and 
suggest alternatives.
    vii. Explain your views as clearly as possible, avoiding the use of 
profanity or personal threats.
    viii. Make sure to submit your comments by the comment period 
deadline identified.

II. Background and Statutory Findings

    In the Federal Register of June 1, 2005 (70 FR 31455) (FRL-7711-8), 
EPA issued a notice under section 408(d)(3) of FFDCA, 21 U.S.C. 
346a(d)(3), announcing the filing of a pesticide petition (PP 3F6569) 
by Gowan Company, 370 S. Main St., Yuma, AZ 85365. The petition 
requested that 40 CFR 180.448 be amended by establishing a tolerance 
for combined residues of the insecticide hexythiazox and its 
metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety (expressed as parent), in or on grapes at 1.0 part 
per million (ppm), raisins at 4.0 ppm, citrus at 0.5 ppm, and citrus 
oil at 2.0 ppm. This notice included a summary of the petition prepared 
by Gowan Company, the registrant. There were no comments received in 
response to the notice of filing.
    EPA is issuing this action as a proposed rule (rather than a final 
rule) because after review of the initial petition and the Notice of 
Filing the Agency has determined that:
     The existing tolerance for apple, wet pomace must be 
revised to 2.5 ppm.
     The existing tolerances for cattle, goat, sheep, and horse 
meat byproducts must be revised to 0.12 ppm.
    EPA has also determined that:
     The existing tolerances for apple and pear can be deleted 
since a tolerance is being proposed for the entire pome fruit group.
     The proposed tolerances for grapes at 1.0 ppm; citrus 
fruit, crop group 10 at 0.5 ppm; and citrus oil at 2.0 ppm should be 
revised to 0.75 ppm, 0.35 ppm, and 0.90 ppm, respectively.
     Tolerances for citrus, dried pulp at 1.5 ppm; and fruit, 
pome, group 11 at 1.7 ppm are necessary.
     The proposed tolerance for raisins is not necessary.
    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. * * 
*''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances of November 26, 1997 (62 FR 62961) 
(FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of FFDCA, for a tolerance for combined residues of 
hexythiazox on grape at 0.75 ppm; citrus fruit, crop group 10 (CA, AZ, 
TX only) at 0.35 ppm; citrus, oil at 0.90 ppm; citrus, dried pulp at 
1.5 ppm; fruit, pome, group 11 at 1.7 ppm; apple, wet pomace at 2.5 
ppm; and cattle, sheep, goat, and horse meat byproducts at 0.12 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 as well 
as the no-observed-adverse-effect-level (NOAEL) and the lowest-
observed-adverse-effect-level (LOAEL) from the toxicity studies 
reviewed are discussed in the Federal Register of April 18, 2001 (66 FR 
19879) (FRL-6778-8). Since that time a micronucleus assay study has 
been submitted and reviewed. Based on the submitted studies hexythiazox 
has been classified as nonmutagenic.

B. Toxicological Endpoints

    The dose at which the NOAEL from the toxicology study identified as 
appropriate for use in risk assessment is used to estimate the 
toxicological level of concern (LOC). However, the lowest dose at which 
adverse effects of concern are identified 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 
inter-species differences and 10X for intra-species differences.
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (aRfD or cRfD) 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 (SF).
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for inter-species differences and 10X for intra-species 
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 106 or one in a million). 
Under certain specific circumstances, MOE calculations will

[[Page 77366]]

be used for the carcinogenic risk assessment. In this non-linear 
approach, a ``point of departure'' is identified below which 
carcinogenic effects are not expected. The point of departure is 
typically a NOAEL based on an endpoint related to cancer effects though 
it may be a different value derived from the dose response curve. To 
estimate risk, a ratio of the point of departure to exposure 
(MOEcancer = point of departure/exposures) is calculated. A 
summary of the toxicological endpoints for hexythiazox used for human 
risk assessment is shown in Table 1 of this unit:

     Table 1.--Summary of Toxicological Dose and Endpoints for Hexythiazox for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                          Dose Used in Risk       FQPA SF and Endpoint   Study and Toxicological
          Exposure Scenario                 Assessment, UF        for Risk Assessment            Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary - females (13-50 years)  NOAEL = 240 mg/kg/day    FQPA SF = 1x             Developmental Toxicity
 of age                                UF = 100...............  aPAD = 2.4 mg/kg/day...   study - rat
                                       aRfD = 2.4 mg/kg/day...                           Developmental LOAEL =
                                                                                          720 mg/kg/day based on
                                                                                          delayed ossification
----------------------------------------------------------------------------------------------------------------
Acute dietary (general population      A dose and endpoint attributable to a single exposure were not identified
 including infants and children)        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 = 0.025 mg/kg/day.   feeding study - dog
                                       cRfD = 0.025 mg/kg/day.                           LOAEL = 12.5 mg/kg/day
                                                                                          based on increased
                                                                                          absolute and relative
                                                                                          adrenal weights and
                                                                                          associated adrenal
                                                                                          histopathology
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      Category C (possible     Q1*= 2.22x10-\2\mg/kg/   Increases in incidence
                                        human carcinogen)        day-\1\                  of malignant and
                                                                                          combined benign/
                                                                                          malignant liver tumors
                                                                                          in female mice
----------------------------------------------------------------------------------------------------------------
Short-term dermal (1-30 days)          Oral maternal NOAEL =    LOC for MOE = 100        Developmental toxicity
 (occupational)                         240 mg/kg/day (dermal    (occupational)           study - rat
                                        absorption rate = 2%)                            LOAEL = 720 mg/kg/day
                                                                                          based on decreased
                                                                                          maternal body weight
                                                                                          gain during gestation
                                                                                          days 7-17 and
                                                                                          decreased food
                                                                                          consumption on
                                                                                          gestation days 9-12
----------------------------------------------------------------------------------------------------------------
Short-term inhalation (1-30            Oral maternal NOAEL=     LOC for MOE = 100        Developmental toxicity
 days)(occupational)                    240 mg/kg/day            (occupational)           study - rat
                                        (inhalation absorption                           LOAEL = 720 mg/kg/day
                                        rate = 100%)                                      based on decreased
                                                                                          maternal body weight
                                                                                          gain during gestation
                                                                                          days 7-17 and
                                                                                          decreased food
                                                                                          consumption on
                                                                                          gestation days 9-12
----------------------------------------------------------------------------------------------------------------

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.448) for the combined residues of hexythiazox, 
in or on a variety of raw agricultural commodities ranging from 0.10-10 
ppm. Tolerances have also been established for these same compounds in/
on milk (0.02 ppm), ruminant fat (0.02 ppm), and ruminant meat 
byproducts (0.02 ppm) as a result of secondary residues. 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 a 1-day or 
single exposure. The LifelineTM (ver. 3.00) and Dietary 
Exposure Evaluation Model - Food Consumption Intake Database (DEEM-
FCIDTM, ver. 2.03) models were used for the assessments. 
Both of these models use food consumption data from the U. S. 
Department of Agriculture (USDA's) 1994-1996, and 1998 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: Tolerance 
level residues, 100% crop treated, and DEEMTM (ver 7.81) 
default processing factors for all plant and livestock residues.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the LifelineTM (ver. 3.00), and DEEM-
FCIDTM, (ver. 2.03) models evaluated the individual food 
consumption as reported by respondents in the USDA 1994-1996 and 1998 
Nationwide Continuing Surveys of Food Intake by Individuals (CSFII) and 
accumulated exposure to the chemical for each commodity. The following 
assumptions were made for the chronic exposure assessments: Average 
percent crop treated (PCT) estimates for several registered 
commodities, projected PCT estimates for proposed commodities, average 
field trial residues, FDA monitoring data for stone fruit (excluding 
cherry) and pome fruit,

[[Page 77367]]

experimentally determined processing factors when available, and 
anticipated livestock residues (dietary burden calculated using average 
field trial and PCT estimates).
    iii. Cancer. The cancer dietary analyses were also conducted using 
the LifelineTM (ver. 3.00), and DEEM-FCIDTM, 
(ver. 2.03) models. The cancer dietary analyses assumed the same plant 
and livestock residues as that of the chronic analyses.
    iv. Anticipated residue and percent crop treated (PCT) information. 
Section 408(b)(2)(E) of FFDCA 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 pursuant 
to section 408(f)(1) 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. For the present action, EPA will 
issue such Data Call-Ins for information relating to anticipated 
residues as are required by FFDCA section 408(b)(2)(E) and authorized 
under FFDCA section 408(f)(1). Such Data Call-Ins will be required to 
be submitted no later than 5 years from the date of issuance of this 
tolerance.
    Section 408(b)(2)(F) of FFDCA 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) of FFDCA, EPA may require registrants to submit 
data on PCT.
    The Agency used PCT information as follows. Average values for PCT 
data were used in the chronic and cancer analyses for the following 
commodities with established tolerances: < 1% for almonds, apples, 
apricots, cherries, prunes, plums, and walnuts; 5% for nectarines, 
peaches, and pears; 10% for dates; and 20% for strawberries. Projected 
average PCT values were used for proposed commodities as follows: 23% 
for grapes and 21% for oranges.
    The Agency believes that the three conditions previously discussed 
have been met. With respect to Condition 1, PCT estimates are derived 
from available federal, state, and private market survey data. For 
existing crop sites on pesticide registrations (``existing use''), EPA 
uses an average PCT for chronic dietary exposure estimates. The average 
PCT figure is derived by combining available federal, state, and 
private market survey data on the existing use, averaging by year, 
averaging across all years, and rounding up to the nearest multiple of 
five except for those situations in which the average PCT is less than 
one. In those cases < 1% is used as the average and < 2.5% is used as the 
maximum. EPA uses a maximum PCT for acute dietary exposure estimates. 
The maximum PCT figure is the single maximum value reported overall 
from available federal, state, and private market survey data on the 
existing use, across all years, and rounded up to the nearest multiple 
of five. In most cases, EPA uses available data from USDA/National 
Agricultural Statistics Service (NASS), Proprietary Market Surveys, and 
the National Center for Food and Agriculture Policy (NCFAP) for the 
most recent six years. The Agency is reasonably certain that the 
percentage of the food treated is not likely to be an underestimation.
    The Agency projects PCT for a new pesticide use by assuming that 
the PCT for the pesticide's initial five years will not exceed the 
average PCT of the dominant pesticide (the one with the largest PCT) 
within its chemical type over three latest available years. For grapes 
hexythiazox was compared with imidacloprid. For oranges, hexythiazox 
was compared with abamectin and S-methoprene. The PCTs included in the 
average may be each for the same pesticide or for different pesticides 
since the same or different pesticides may dominate for each year 
selected. Typically, EPA uses USDA/NASS as the source for raw PCT data 
because it is non-proprietary and directly available without 
computation. This method of projecting PCT for a new pesticide, with or 
without regard to specific pest(s), produces an upper-end projection 
that is unlikely, in most cases, to be exceeded in actuality because 
the dominant pesticide is well-established and accepted by farmers. 
Factors that bear on whether a projection based on the dominant 
pesticide could be exceeded are whether the new pesticide is more 
efficacious or controls a broader spectrum of pests than the dominant 
pesticide within its similar type, whether it is more cost-effective 
than the dominant pesticide, and whether it is likely to be readily 
accepted by growers and experts.
    As to Conditions 2 and Condition 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, 
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.

[[Page 77368]]

    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.
    The acute, chronic, and cancer analyses incorporated modeled 
surface water and/or ground water estimates generated using PRZM/EXAMS 
and SCI-GROW, respectively. The SCI-GROW model evaluated the highest 
registered/proposed application rate. The PRZM/EXAMS model evaluated 
all registered/proposed application scenarios. The PRZM/EXAMS 
evaluation considered potential spatial variation by using model 
scenarios which represent a combination of specific agronomic, soil, 
and climatological parameters which are geographically specific.
    Based on the PRZM/EXAMS and SCI-GROW models the estimated drinking 
water concentrations (EDWCs) of hexythiazox for acute exposures are 
estimated to be 4.23 parts per billion (ppb) for surface water and 
0.00503 ppb for ground water. The EDWCs for chronic exposures are 
estimated to be 2.26 ppb for surface water and 0.00503 ppb for ground 
water. The EDWCs for cancer are estimated to be 1.72 ppb for surface 
water and 0.00503 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 effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    Unlike other pesticides for which EPA has followed a cumulative 
risk approach based on a common mechanism of toxicity, EPA has not made 
a common mechanism of toxicity finding as to hexythiazox and any other 
substances and 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 policy statements released by EPA's Office of 
Pesticide Programs concerning common mechanism determinations and 
procedures for cumulating effects from substances found to have a 
common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/
.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of FFDCA provides that EPA shall apply 
an additional tenfold margin of safety for infants and children in the 
case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. The prenatal and postnatal 
toxicology data base indicates no increased susceptibility of rats or 
rabbits to in utero and/or postnatal exposure to hexythiazox.
    3. Conclusion. EPA determined that the special FQPA SF to protect 
infants and children should be removed. The recommendation is based on 
the following:
     The toxicology data base for hexythiazox is considered 
complete for selecting toxicity endpoints for risk assessment. The 
toxicity profile of hexythiazox can be characterized for all effects, 
including potential developmental, reproductive and neurotoxic effects.
     Exposure data are complete or are estimated based on data 
that reasonably accounts for potential exposures.
     There is no evidence of increased susceptibility of rats 
or rabbits to in utero and/or postnatal exposure to hexythiazox.

E. Aggregate Risks and Determination of Safety

    Acute, chronic, and cancer modeled drinking water estimates were 
incorporated directly into the aggregate dietary analysis, rather than 
using back-calculated drinking water levels of comparison (DWLOCs). EPA 
is no longer comparing EDWCs generated by water quality models with 
DWLOCs. Instead, EPA is now directly incorporating the actual water 
quality model output concentrations into the risk assessment. This 
method of incorporating water concentrations into our aggregate 
assessments relies on actual CSFII-reported drinking water consumption 
and more appropriately reflects the full distribution of drinking water 
concentrations.
    The acute analysis assumed the PRZM/EXAMS 1 in 10-year annual peak 
drinking water concentration. The chronic analysis assumed the PRZM/
EXAMS 1 in 10-year annual mean concentration. These estimates were 
higher than the SCI-GROW estimates.
    The DEEM-FCIDTM cancer analysis assumed the PRZM/EXAMS 
30-year annual mean concentration (which was higher than the SCI-GROW 
estimate). Since LifelineTM allows for the assignment of 
different drinking water concentrations for those individuals in 
households with private wells, the LifelineTM analysis 
incorporated both the PRZM/EXAMS 30-year annual mean concentration and 
the SCI-GROW concentration. The LifelineTM analysis assumed 
the SCI-GROW concentration for individuals obtaining drinking water 
from individual wells and the PRZM/EXAMS 30-year annual mean 
concentration for individuals in households receiving drinking water 
from public water systems and other sources.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the resulting LifelineTM and DEEM-
FCIDTM exposure estimates were <1% of the aPAD for females 
13-49 years old. An acute endpoint for the remaining population 
subgroups was not identified. EPA does not expect the aggregate 
exposure to exceed 100% of the aPAD, as shown in Table 2 of this unit:

[[Page 77369]]

                              Table 2.--Aggregate Risk Assessment for Acute Exposure to Hexythiazox (Food + Drinking Water)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                              %aPAD                         Exposure (mg/kg/day)
                   Population Subgroup                      aPAD (mg/kg/day) ---------------------------------------------------------------------------
                                                                                  DEEM-FCID           Lifeline          DEEM-FCID           Lifeline
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13-49 years old)                                                2.4                 < 1                 < 1           0.010176             0.0120
--------------------------------------------------------------------------------------------------------------------------------------------------------

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, the resulting LifelineTM and 
DEEM-FCIDTM exposure estimates were <1% of the cPAD for the 
U.S. population, < 1% of the cPAD for all infants and 1% of the cPAD for 
children 1-2 years old, the children subpopulation at greatest 
exposure]. There are no residential uses for hexythiazox that result in 
chronic residential exposure to hexythiazox. EPA does not expect the 
aggregate exposure to exceed 100% of the cPAD, as shown in Table 3 of 
this unit:

                      Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Hexythiazox (Food + Drinking Water)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                              %cPAD                         Exposure (mg/kg/day)
                   Population Subgroup                      cPAD (mg/kg/day) ---------------------------------------------------------------------------
                                                                                  DEEM-FCID           Lifeline          DEEM-FCID           Lifeline
--------------------------------------------------------------------------------------------------------------------------------------------------------
General U.S. population                                                0.025                 < 1                 < 1           0.000110           0.000094
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants < (1 year old)                                              0.025                 < 1                 < 1           0.000217           0.000185
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1-2 years old)                                               0.025                  1                  1           0.000267           0.000251
--------------------------------------------------------------------------------------------------------------------------------------------------------

    3. Aggregate cancer risk for U.S. population. Based on the exposure 
assumptions described in this unit the resulting cancer DEEM-
FCIDTM and LifelineTM dietary exposure estimates 
for the U.S. population yielded a cancer risk of 2.30 in 1 million and 
2.03 in 1 million, respectively. DEEM-FCIDTM resulted in a 
higher cancer risk estimate due to differing drinking water assumptions 
described in this unit (LifelineTM permits incorporation of 
the entire PRZM-EXAMS distribution when conducting a cancer analysis 
while DEEM-FCIDTM permits only a point estimate). Based on a 
the DEEM-FCIDTM analysis, the major contributors to the 
cancer risk were water (35% of total exposure), strawberry (15% of 
total exposure), grape (14% of total exposure), field corn (13% of 
total exposure), citrus (9% of total exposure), caneberry (5% of total 
exposure), and hop (5% of total exposure). The remaining commodities 
combined for 4% of the total exposure.
    Under the reasonable certainty of no harm standard in FFDCA section 
408(b)(2)(A)(ii), cancer risks must be no greater than negligible. EPA 
has consistently interpreted negligible cancer risks to be risks within 
the range of an increased cancer risk of 1 in 1 million. Risks as high 
as 3 in 1 million have been considered to be within this risk range. 
EPA concludes that the estimated cancer risk for hexythiazox is within 
the negligible risk range. The Agency notes that hexythiazox has been 
classified as a possible human carcinogen based on increased incidence 
of liver tumors in female mice. No chemical-related oncogenic effects 
were reported in male mice or in male and female rats, and hexythiazox 
has been classified as nonmutagenic. A summary of the cancer dietary 
exposure estimates for hexythiazox are shown in Table 4 of this unit:

                              Table 4.--Aggregate Cancer Dietary Exposure and Risk for Hexythiazox (Food + Drinking Water)
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                      Exposure (mg/kg/day)                          Risk
                   Population Subgroup                            Q1*1       ---------------------------------------------------------------------------
                                                                                  DEEM-FCID           Lifeline          DEEM-FCID           Lifeline
--------------------------------------------------------------------------------------------------------------------------------------------------------
General U.S. population                                                0.022           0.000104            0.00091        2.30 x 10-6        2.03 x 10-6
--------------------------------------------------------------------------------------------------------------------------------------------------------

    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, and to infants and children from aggregate 
exposure to hexythiazox residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    The Pesticide Analytical Manual Volume II (PAM II) of the Food and 
Drug Administration (FDA) includes suitable analytical methods for the 
determination of hexythiazox and metabolites containing the (4-
chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (AMR-985-87) in pome 
fruit, grape, and citrus, livestock tissue, and milk.

B. International Residue Limits

    The Codex and EPA tolerance expression differ; therefore, 
harmonization is not possible

C. Conditions

    As a condition of registration the registrant must submit the 
following data:
     Apple and pear field trial data for the emulsifiable 
concentrate (EC) formulation. The recommended tolerance may 
overestimate actual expected residues following application of 
hexythiazox as labeled since is based on an exaggerated rate from the 
wettable powder residue trial and the maximum factor by which the EC 
formulation

[[Page 77370]]

exceeded the WP formulation in the apple side-by-side field trials.
     An orange processing study.

V. Conclusion

    Tolerances are proposed for combined residues of 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 grape at 
0.75 ppm; citrus fruit, crop group 10 (CA, AZ, TX only) at 0.35 ppm; 
citrus, oil at 0.90 ppm; citrus, dried pulp at 1.5 ppm; fruit, pome, 
group 11 at 1.7 ppm; apple, wet pomace at 2.5 ppm; and cattle, sheep, 
goat, and horse meat byproducts at 0.12 ppm.

VI. Statutory and Executive Order Reviews

    This proposed rule establishes a tolerance under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this proposed rule has 
been exempted from review under Executive Order 12866 due to its lack 
of significance, this proposed rule is not subject to Executive Order 
13211, Actions Concerning Regulations That Significantly Affect Energy 
Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This proposed 
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). Pursuant to the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.), the Agency hereby certifies that this proposed 
action will not have significant negative economic impact on a 
substantial number of small entities. Establishing a tolerance, in 
effect, removes the statutory bar on the use of a pesticide on the 
specified crops and thus has no negative economic impact. 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 proposed rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. For these same reasons, the Agency has 
determined that this proposed rule does not have any ``tribal 
implications'' as described in Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 6, 2000). Executive Order 13175, requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by tribal officials in the development of regulatory policies that have 
tribal implications.'' ``Policies that have tribal implications'' is 
defined in the Executive Order to include regulations that have 
``substantial direct effects on one or more Indian tribes, on the 
relationship between the Federal Government and the Indian tribes, or 
on the distribution of power and responsibilities between the Federal 
Government and Indian tribes.'' This proposed 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 proposed rule.

List of Subjects in 40 CFR Part 180

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

    Dated: December 22, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
    Therefore, it is proposed that 40 CFR chapter I be 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), 346a and 371.
    2. Section 180.448 is amended by removing the commodities ``apple'' 
and ``pear'' and alphabetically adding new commodities to the table in 
paragraphs (a) and (c) to read as follows:

Sec.  180.448  Hexythiazox; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Citrus, dried pulp...................................                1.5
Citrus, oil..........................................               0.90
                                * * * * *
Fruit, pome, group 11................................                1.7
                                * * * * *
Grape................................................               0.75
                                * * * * *
------------------------------------------------------------------------

* * * * *
    (c) * * *

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Fruit, citrus group 10 (CA, AZ, TX only).............               0.35
------------------------------------------------------------------------

* * * * *
    3. Section 180.448 is amended by revising the following commodities 
in the table in paragraph (a) to read as follows:

Sec.  180.448  Hexythiazox; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Apple, wet pomace....................................                2.5

[[Page 77371]]

                                * * * * *
Cattle, meat byproducts..............................               0.12
                                * * * * *
Goat, meat byproducts................................               0.12
                                * * * * *
Horse, meat byproducts...............................               0.12
                                * * * * *
Sheep, meat byproducts...............................               0.12
------------------------------------------------------------------------

* * * * *
 [FR Doc. E5-8037 Filed 12-29-05; 8:45 am]

BILLING CODE 6560-50-S