[Federal Register Volume 69, Number 32 (Wednesday, February 18, 2004)]
[Rules and Regulations]
[Pages 7596-7606]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3371]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

OPP-2003-0389; FRL-7341-6]


Aminoethoxyvinylglycine hydrochloride (aviglycine HCl); Pesticide 
Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes a tolerance for residues of 
aminoethoxyvinylglycine hydrochloride (aviglycine HCl) in or on apple, 
pear and the stone fruits crop group 12, excepting cherries. Valent 
BioSciences Corporation requested this tolerance under the Federal 
Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality 
Protection Act of 1996 (FQPA).

DATES: This regulation is effective February 18, 2004. Objections and 
requests for hearings, identified by docket ID number OPP-2003-0389, 
must be received on or before April 19, 2004.

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

FOR FURTHER INFORMATION CONTACT: Denise Greenway, Biopesticides and 
Pollution Prevention Division (7511C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001; telephone number: (703) 308-8263; e-mail 
address:[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 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 Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0389. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public

[[Page 7597]]

docket is the collection of materials that is available for public 
viewing at the Public Information and Records Integrity Branch (PIRIB), 
Rm. 119, Crystal Mall 2, 1921 Jefferson Davis Hwy., Arlington, 
VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday 
through Friday, excluding legal holidays. The docket telephone number 
is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html/, a 
beta site currently under development. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of November 13, 2003 (68 FR 64343) (FRL-
7333-6), EPA issued a notice pursuant to section 408 of FFDCA, 21 
U.S.C. 346a, as amended by FQPA (Public Law 104-170), announcing the 
filing of a pesticide petition (PP 6F4632, transferred from Abbott 
Laboratories) by Valent BioSciences Corporation, 870 Technology Way, 
Libertyville, IL 60048. That notice included a summary of the petition 
prepared by Valent BioSciences Corporation, the registrant. There were 
no comments received in response to the notice of filing.
    In the Federal Register of November 19, 2003 (68 FR 65281) (FRL-
7334-3), EPA issued a notice pursuant to section 408 of FFDCA, 21 
U.S.C. 346a, as amended by FQPA (Public Law 104-170), announcing the 
filing of a pesticide petition (PP 3F6772) by Valent BioSciences 
Corporation, 870 Technology Way, Libertyville, IL 60048. That notice 
included a summary of the petition prepared by Valent BioSciences 
Corporation, the registrant. There were no comments received in 
response to the notice of filing.
    The petitions requested that 40 CFR 180.502 be amended by 
establishing permanent tolerances for residues of the biochemical 
pesticide aminoethoxyvinylglycine hydrochloride (aviglycine HCl), 
formerly designated as aminoethoxyvinylglycine (AVG), in or on apple 
and pear at 0.08 parts per million (ppm) (PP 6F4632), and in or on the 
stone fruits crop group 12, excepting cherries, at 0.170 ppm (PP 
3F6772). Data submitted and summarized by Valent BioSciences 
Corporation in these petitions include: Domestically and 
internationally generated residue data; another acute inhalation 
toxicity study; and subchronic toxicity (rat, mouse and dog), and 
metabolism (rat and comparative mouse and rat) studies, as well as a 
Tier III biochemical pesticide toxicity study (rat carcinogenicity), 
and additional studies (rabbit developmental toxicity and rat chronic 
toxicity) to refine assessments of subpopulation sensitivities and 
carcinogenic potential.
    Previously, in support of both time-limited and temporary 
tolerances issued by EPA for residues of aviglycine HCl in or on apple, 
pear, and the stone fruits crop group 12 (May, 7, 1997, 62 FR 24835, 
FRL-5713-3, corrected on October 29, 1997, 62 FR 56089, FRL-5751-5; 
June 10, 1999, 64 FR 31124, FRL-6080-4; July 12, 2001, 66 FR 36477, 
FRL-6788-7; and July 12, 2001, 66 FR 36481, FRL-6790-7), residue 
studies and toxicity data consistent with the Tier I biochemical 
pesticide toxicity data requirements, as described in 40 CFR 
158.690(c), were submitted. That data included acute oral, dermal and 
inhalation toxicity studies; eye and skin irritation studies; dermal 
sensitization and one genotoxicity study (Ames test); and subchronic 
(immunotoxicity) and developmental toxicity studies in the rat. Several 
additional toxicity studies, although not required for biochemical 
pesticides, also were submitted previously, including two mammalian 
mutagenicity studies (Tier II rat micronuclei and mouse lymphoma) and 
subchronic studies (including 21-day dermal toxicity) in the rat. In 
addition, a conditionally required 2-generation rat reproduction study 
was submitted previously to reduce the uncertainties associated with 
the assessment of susceptibility of infants and children to potential 
hazards from aviglycine HCl exposure. All of this toxicity data on 
aviglycine HCl, both the new data submitted with the new petitions 
considered in this final rule and the data previously submitted and 
mentioned above has been considered and factored into the action taken 
in this final rule.
    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 (62 FR 62961, November 26, 1997) (FRL-
5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of 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 tolerances for residues of aviglycine HCl on 
apple and pear at 0.08 ppm, and on the stone fruits crop group 12, 
excepting cherries, at 0.170 ppm. EPA's assessment of exposures and 
risks associated with establishing these tolerances follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by aviglycine HCl

[[Page 7598]]

are discussed in Table 1 of this unit as well as the no observed 
adverse effect level (NOAEL) and the lowest observed adverse effect 
level (LOAEL) from the toxicity studies reviewed.
    The acute toxicity studies indicated low toxicity for technical 
aviglycine HCl, placing it into Toxicity Category III for dermal 
toxicity, and Toxicity Category IV for oral toxicity and eye and skin 
irritation. A new acute inhalation toxicity study considered as part of 
this action changed the technical grade material's classification from 
Toxicity Category III to Toxicity Category IV. Dermal sensitization 
studies also indicated that aviglycine HCl is a non-sensitizer. 
Finally, in order to comply with the statutory requirements under FIFRA 
section 6(a)(2) and EPA's data requirements (40 CFR section 
158.690(c)), any incident of hypersensitivity associated with use of 
aviglycine HCl must be reported to the Agency.

            Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
         Guideline No.               Study Type            Results
------------------------------------------------------------------------
870.3100                         90-Day oral         NOAEL = 2.2
                                  toxicity-rat        milligram/kilogram/
                                                      day (mg/kg/day)
                                                      for females, 9.2
                                                      mg/kg/day (highest
                                                      dose tested) for
                                                      males
                                                     LOAEL = 9.4 mg/kg/
                                                      day (the highest
                                                      dose tested for
                                                      females) based on
                                                      reduced body
                                                      weight gain, food
                                                      consumption and
                                                      food efficiency;
                                                      increased severity
                                                      and incidence of
                                                      reversible kidney
                                                      and liver effects;
                                                      and discoloration
                                                      of the liver
-----------------------------------------------------
870.3100                         90-Day oral         NOAEL = 0.4 mg/kg/
                                  toxicity-rat        day for males and
                                                      females
                                                     LOAEL = 4.0 mg/kg/
                                                      day for males and
                                                      females, based on
                                                      increased
                                                      incidence of
                                                      periportal
                                                      hepatocellular
                                                      vacuolation in the
                                                      liver
-----------------------------------------------------
870.3100                         90-Day oral         NOAEL = 9.5 mg/kg/
                                  toxicity-mouse      day for males and
                                                      9.6 mg/kg/day for
                                                      females
                                                     LOAEL = 23.4 mg/kg/
                                                      day for males and
                                                      23.2 mg/kg/day for
                                                      females based on
                                                      clinical signs in
                                                      both sexes,
                                                      decreased mean
                                                      body weight and
                                                      body weight gain
                                                      in males,
                                                      decreased relative
                                                      spleen and kidney
                                                      weights in males,
                                                      histopathology in
                                                      the adrenal glands
                                                      of females, and
                                                      increased
                                                      testicular atrophy
                                                      in males
-----------------------------------------------------
870.3150                         90-Day oral         NOAEL = 0.6 mg/kg/
                                  toxicity-dog        day
                                                     LOAEL = 1.2 mg/kg/
                                                      day based on
                                                      decreased body
                                                      weight gain, food
                                                      consumption,
                                                      uterine weights,
                                                      and liver
                                                      pathology
-----------------------------------------------------
870.3200                         21-Day dermal       NOAEL = 1,000 mg/kg/
                                  toxicity-rat        day (limit dose)
                                                     A LOAEL was not
                                                      determined. Limit
                                                      doses are as high
                                                      a dose level as
                                                      can practically be
                                                      tested; when there
                                                      are no effects, a
                                                      LOAEL is not
                                                      needed
-----------------------------------------------------
870.3700                         Prenatal            Maternal NOAEL =
                                  developmental-rat   1.77 mg/kg/day
                                                     LOAEL = 8.06 mg/kg/
                                                      day based on
                                                      decreased body
                                                      weight gain, food
                                                      consumption,
                                                      defecation, and
                                                      the presence of
                                                      perinasal red
                                                      material
                                                     Developmental NOAEL
                                                      = 1.77 mg/kg/day
                                                     LOAEL = 8.06 mg/kg/
                                                      day based on
                                                      decreased mean
                                                      fetal body weights
                                                      and developmental
                                                      skeletal variants
-----------------------------------------------------
870.3700                         Prenatal            Maternal NOAEL =
                                  developmental-      0.4 mg/kg/day
                                  rabbit             LOAEL = 0.7 mg/kg/
                                                      day based on
                                                      decreased body
                                                      weight gains and
                                                      food consumption
                                                     Developmental NOAEL
                                                      = 0.2 mg/kg/day
                                                     LOAEL = 0.4 mg/kg/
                                                      day based on the
                                                      presence of
                                                      developmental
                                                      malformations
-----------------------------------------------------
870.3800                         Reproduction and    Parental/Systemic
                                  fertility effects-  NOAEL = 0.8 mg/kg/
                                  rat                 day for males, 2.5
                                                      mg/kg/day for
                                                      females
                                                     LOAEL = 2.5 mg/kg/
                                                      day based on
                                                      decreased absolute
                                                      body weight and
                                                      body weight gain,
                                                      and periportal
                                                      hepatocellular
                                                      vacuolation in the
                                                      liver in F0 and F1
                                                      adult males; 4 mg/
                                                      kg/day for females
                                                      based on decreased
                                                      absolute body
                                                      weights, body
                                                      weight gain and
                                                      food consumption
                                                      in F1 generation
                                                     Reproductive NOAEL
                                                      = 4 mg/kg/day
                                                     LOAEL = 8 mg/kg/day
                                                      based on decreased
                                                      testicular weight,
                                                      changes in sperm
                                                      morphology, etc.,
                                                      and increased
                                                      incidence of
                                                      testicular
                                                      histopathology
                                                     Offspring NOAEL =
                                                      2.5 mg/kg/day
                                                     LOAEL = 4 mg/kg/day
                                                      based on decreased
                                                      viability of F1
                                                      pups and retarded
                                                      growth in F1 and
                                                      F2 pups
-----------------------------------------------------

[[Page 7599]]

 
870.4100                         Chronic toxicity-   NOAEL = 0.7 mg/kg/
                                  rat (1-year         day for males and
                                  feeding)            females
                                                     LOAEL = 7.0 mg/kg/
                                                      day for males and
                                                      females based on
                                                      the increased
                                                      incidence of
                                                      testicular atrophy
                                                      in males and
                                                      chronic renal
                                                      nephropathy in
                                                      females, and
                                                      decreased food
                                                      consumption and
                                                      body weight gain
                                                      in both sexes
-----------------------------------------------------
870.4200                         Carcinogenicity-    NOAEL = 0.7 mg/kg/
                                  rat                 day
                                                     LOAEL = 7.0 mg/kg/
                                                      day based on
                                                      decreased absolute
                                                      body weights, body
                                                      weight gains, and
                                                      food consumption,
                                                      decreased survival
                                                      and earlier deaths
                                                      in males, clinical
                                                      signs (unkempt
                                                      coat, hunched
                                                      posture, rolling
                                                      gait,
                                                      piloerection, and/
                                                      or walking on tip
                                                      toes), cataracts,
                                                      adverse effects on
                                                      male reproductive
                                                      organs (testicular
                                                      degeneration,
                                                      atrophied seminal
                                                      vesicles, and
                                                      decreased prostate
                                                      weight), adverse
                                                      effects on the
                                                      exocrine pancreas
                                                      in females
                                                      (lobular/acinar
                                                      cell atrophy,
                                                      focal hyperplasia,
                                                      and focal
                                                      basophilic
                                                      alteration), and
                                                      an increased
                                                      incidence of focal
                                                      medullary cell
                                                      hyperplasia of the
                                                      adrenal gland in
                                                      females. For
                                                      further
                                                      discussion, see
                                                      Unit III.C.iii. of
                                                      this final rule.
-----------------------------------------------------
870.5100 Ames                    Gene mutation       There was no
                                                      mutagenic activity
-----------------------------------------------------
870.5300 Mouse lymphoma          Gene mutation       There was no
                                                      mutagenic activity
-----------------------------------------------------
870.5395 Micronuclei             Cytogenetics        There was no
                                                      evidence of
                                                      chromosomal damage
-----------------------------------------------------
870.7800                         Immunotoxicity-rat  NOAEL = 5 mg/kg/day
                                                     LOAEL = 15 mg/kg/
                                                      day based on the
                                                      decreased primary
                                                      antibody (IgM)
                                                      response to sheep
                                                      red blood cells;
                                                      decreased absolute
                                                      and relative
                                                      thymus weights;
                                                      decreased body
                                                      weight, food
                                                      consumption and
                                                      food efficiency at
                                                      the high dose
                                                      level. (While this
                                                      study did not
                                                      fully meet the
                                                      requirements
                                                      outlined in the
                                                      Pesticide
                                                      Assessment
                                                      Guidelines
                                                      Subdivision M
                                                      OPPTS Series 152-
                                                      18, because a
                                                      NOAEL and LOAEL
                                                      were determined,
                                                      and found to be
                                                      consistent with
                                                      those from other
                                                      repeat-dose
                                                      studies, EPA
                                                      determined that
                                                      the study need not
                                                      be repeated.)
-----------------------------------------------------
                                 Special studies:    No significant
                                  Reporter Gene       changes in the
                                  Assays Using        level of reporter
                                  Human Estrogen      activity was
                                  and Androgen        associated with
                                  Receptors, Non-     any concentration
                                  guideline Study     of aviglycine HCl
                                                      when tested with
                                                      or without
                                                      estrogenic or
                                                      androgenic
                                                      inhibitors.
                                                      Aviglycine HCl was
                                                      not cytotoxic at
                                                      any concentration.
------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (the NOAEL) from 
the toxicology study identified as appropriate for use in risk 
assessment is used to estimate the toxicological level of concern 
(LOC). However, the lowest dose at which adverse effects of concern are 
identified (the LOAEL) is sometimes used for risk assessment if no 
NOAEL was achieved in the toxicology study selected. An uncertainty 
factor (UF) is applied to reflect uncertainties inherent in the 
extrapolation from laboratory animal data to humans and in the 
variations in sensitivity among members of the human population as well 
as other unknowns. An UF of 100 is routinely used, 10X to account for 
interspecies differences and 10X for intraspecies differences.
    Three other types of safety or uncertainty factors may be used: 
``Traditional uncertainty factors;'' the ``special FQPA safety 
factor;'' and the ``default FQPA safety factor.'' By the term 
``traditional uncertainty factor,'' EPA is referring to those 
additional uncertainty factors used prior to FQPA passage to account 
for database deficiencies. These traditional uncertainty factors have 
been incorporated by the FQPA into the additional safety factor for the 
protection of infants and children. The term ``special FQPA safety 
factor'' refers to those safety factors that are deemed necessary for 
the protection of infants and children primarily as a result of the 
FQPA. The ``default FQPA safety factor'' is the additional 10X safety 
factor that is mandated by the statute unless it is decided that there 
are reliable data to choose a different additional factor (potentially 
a traditional uncertainty factor or a special FQPA safety factor).
    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 an UF of 
100 to account for interspecies and intraspecies differences and any 
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). 
Where a special FQPA safety factor or the default FQPA safety factor is 
used, 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 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

[[Page 7600]]

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). An example of how such a probability risk is expressed 
would be to describe the risk as one in one hundred thousand (1 X 
10-\5\), one in a million (1 X 10-\6\), or one in 
ten million (1 X 10-\7\). Under certain specific 
circumstances, MOE calculations will be used for the carcinogenic risk 
assessment. In this non-linear approach, a ``point of departure'' is 
identified below which carcinogenic effects are not expected. The point 
of departure is typically a NOAEL based on an endpoint related to 
cancer effects though it may be a different value derived from the dose 
response curve. To estimate risk, a ratio of the point of departure to 
exposure (MOEcancer = point of departure/exposures) is 
calculated.
    A summary of the toxicological endpoints for aviglycine HCl used 
for human risk assessment is shown in Table 2 of this unit:

    Table 2.--Summary of Toxicological Dose and Endpoints for Aviglycine HCl for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                          Dose Used in Risk       Special FQPA SF1 and   Study and Toxicological
          Exposure Scenario                 Assessment, UF      LOC for Risk Assessment          Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary                          NOAEL = 0.2 mg/kg/day    FQPA SF = 1X             Rabbit Developmental
(Females 13-49 years of age)2........  UF = 100...............  aPAD = acute RfD / FQPA   Toxicity
                                       Acute RfD..............   SF.                     Developmental LOAEL =
                                       = 0.002 mg/kg/day......  = 0.002 mg/kg/day......   0.4 mg/kg/day based on
                                                                                          increased occurrence
                                                                                          of developmental
                                                                                          malformations (i.e.
                                                                                          lobular agenesis of
                                                                                          right lung) in the
                                                                                          high and medium dose
                                                                                          groups
----------------------------------------------------------------
Acute Dietary                          NOAEL = 0.2 mg/kg/day    FQPA SF = 1X             Endpoints from rabbit
(General population including infants  UF = 100...............  aPAD = acute RfD / FQPA   developmental study
 and children).                        Acute RfD..............   SF.                      utilized as a worst
                                       = 0.002 mg/kg/day......  = 0.002 mg/kg/day......   case estimate, even
                                                                                          though no acute
                                                                                          toxicological
                                                                                          endpoints resulting
                                                                                          from a single dose
                                                                                          were identified for
                                                                                          populations other than
                                                                                          females 13-49 years of
                                                                                          age.
----------------------------------------------------------------
Chronic Dietary                        NOAEL= 0.8 mg/kg/day     FQPA SF = 1X             Rat 2-generation
(All populations)....................  UF = 100...............  cPAD = chronic RfD /      Reproductive Toxicity
                                       Chronic RfD............   FQPA SF.                LOAEL = 2.5 mg/kg/day
                                       = 0.008 mg/kg/day......  = 0.008 mg/kg/day......   based on decreased
                                                                                          absolute body weight
                                                                                          and body weight gain,
                                                                                          and periportal
                                                                                          hepatocellular
                                                                                          vacuolation in the
                                                                                          liver in F0 and F1
                                                                                          adult males.
----------------------------------------------------------------
Carcinogenicity (general population)   Non-linear Effects       FQPA considerations      Rat carcinogenicity
                                       NOAEL = 0.7 mg/kg/day..   have been accounted     LOAEL = 7.0 mg/kg/day
                                       UF = 1,000 (includes      for in discussions       based on increased
                                        10X for database         involving threshold      incidence of benign
                                        uncertainty3).           non-carcinogenic         testicular
                                       Cancer RfD = 0.0007 mg/   effects3                 interstitial cell
                                        kg/day.                                           adenomas, benign
                                                                                          adrenal
                                                                                          pheochromocytoma, and
                                                                                          adrenal medullary cell
                                                                                          hyperplasia. Decreased
                                                                                          number of animals with
                                                                                          tumors, with benign
                                                                                          tumors, and with
                                                                                          malignant tumors were
                                                                                          also observed. These
                                                                                          decreases were evident
                                                                                          as mammary
                                                                                          fibroadenomas, thyroid
                                                                                          C-cell adenomas, and
                                                                                          anterior pituitary
                                                                                          adenomas.
----------------------------------------------------------------------------------------------------------------
1 The reference to the FQPA safety factor refers to any additional safety factor retained due to concerns unique
  to the FQPA. (See discussion on FQPA safety factor under Unit III.B. of this Final Rule.)
2 The only acute endpoint was identified in pregnant rabbits; therefore, it applies to females 13-49 years of
  age, which includes potentially pregnant individuals. Fetal malformations observed in the developmental study
  are presumed to occur after maternal exposure to a single dose. Utilization of the acute developmental
  endpoint for other populations (general U.S., children 1-2 years old, etc.) substantially over-estimates risk
  because resultant malformations are unique to particular stages of fetal development and will not occur in
  these other populations.
3 Data are inadequate for the determination of human carcinogenic potential. As a result, an additional 10X
  uncertainty factor (UF) was incorporated into hazard estimates for aviglycine HCl's threshold carcinogen
  effects in order to compensate for this inadequacy, increasing the overall UF to 1,000. When applied to the
  NOAEL of 0.7 mg/kg/day, it resulted in a cancer RfD of 0.0007 mg/kg/day. Justification for the utilization of
  an additional 10X uncertainty factor for database insufficiencies in cancer risk assessments included: (i) A
  cancer study in a second species (mouse) was absent, (ii) carcinogenic properties were associated with
  excessive toxicity, (iii) tumor evidence was inconsistent/equivocal, (iv) carcinogenicity potential was not
  confirmed with mutagenicity, endocrine, or immunotoxicity studies, and (v) resultant tumors were not
  associated with target organ (liver) or mechanism of action (pyridoxal 5'-phosphate-dependent enzyme
  inhibition).

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.502) for the residues of aviglycine HCl, in or 
on a variety of raw agricultural commodities. Time-limited tolerances 
for apple and pear, and a temporary tolerance for the stone fruits crop 
group 12 (all expired on December 21, 2003), were established 
previously (July 12, 2001, 66 FR 36481, FRL-6790-7 (apple and pear) and 
July 12, 2001, 66 FR 36477, FRL-6788-7 (stone fruits crop group12)). In 
response to Valent BioSciences Corporation's petitions for permanent 
tolerances, an updated risk assessment was conducted by EPA to assess 
dietary exposures from aviglycine HCl 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.
    In conducting the acute dietary risk assessment EPA used the 
Dietary

[[Page 7601]]

Exposure Evaluation Model software with the Food Commodity Intake 
Database (DEEM-FCID\TM\), which incorporates food consumption data 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 acute exposure assessments: The residue 
of concern for the acute analysis is aviglycine HCl. The assessment 
assumed 100% of the proposed crops were treated, and that all treated 
crops had residues of concern at the requested tolerance levels. 
Anticipated residues were not used. Acute dietary risks for the 95th 
percentile of females 13-49 years old and the general U.S. population 
were minimal and did not exceed EPA's LOC. Acute dietary risks for 
children 1-2 years old technically exceeded EPA's LOC by a small 
margin. These risks represented a worst case scenario using toxicologic 
endpoints that only occurred in utero. Therefore, the calculated risks 
were illustrative at best. See footnote 2 of Table 2 for further 
explanation of acute endpoint utilized by EPA.
    ii. Chronic exposure. In conducting the chronic dietary risk 
assessment EPA used the DEEM-FCID\TM\, which incorporates food 
consumption data as reported by respondents in the USDA 1994-1996 and 
1998 Nationwide CSFII, and accumulated exposure to the chemical for 
each commodity. The following assumptions were made for the chronic 
exposure assessments: The residue of concern for the chronic analysis 
is aviglycine HCl. Conservative chronic dietary assessments utilized 
tolerance-level concentrations for crops (i.e., 0.08 ppm for apple and 
pear and 0.170 ppm for stone fruits crop group 12, excepting cherries). 
Chronic dietary risk for the U.S. population, and children 1-2 years 
old did not exceed 1.6%, and 10.5%, respectively, of the chronic 
Population Adjusted Dose (cPAD, 0.008 mg/kg/day). Therefore, chronic 
dietary risks were minimal and did not exceed EPA's LOC.
    iii. Carcinogenicity. Conflicting evidence for carcinogenicity has 
been reported for aviglycine HCl. Mutatgenicity, immunotoxicology, 
endocrine, subchronic, and chronic feeding studies strongly suggest 
that aviglycine HCl does not induce cancer. Effects observed in the 
carcinogenicity study, such as a threshold-response and reduction in 
the number of animals with tumors, with benign tumors, and with 
malignant tumors also support non-carcinogenic conclusions. In 
contrast, increased incidence of benign testicular interstitial cell 
adenomas, benign adrenal pheochromocytoma, and adrenal medullary cell 
hyperplasia suggest that aviglycine HCl may induce cancer. These 
effects, however, were seen only at an excessively toxic dose and may 
have been mediated indirectly through generic toxic mechanisms such as 
glutathione depletion and resultant oxygen radical-induced cell damage, 
rather than by aviglycine HCl. Dosing with excessive aviglycine HCl, 
therefore, weakened support for carcinogenic activity.
    In the end, weight-of-evidence suggests that aviglycine HCl is non-
carcinogenic. However, definitive statements of carcinogenicity can not 
be made at the current time, because information meeting rigorous 
criteria for defining it as non-carcinogenic (such as a second cancer 
study in a different species and strong non-conflicting evidence) is 
absent. These studies are not typically required in the testing of 
biochemical pesticides. To account for this, an additional database 
uncertainty factor of 10X was integrated with other UFs (100X) 
(increasing the overall uncertainty factor to 1,000) and the NOAEL 
established in the carcinogenesis study (0.7 mg/kg/day) to 
conservatively account for this deficiency (RfD = 0.0007 mg/kg/day).
    Carcinogenic dietary risks for the U.S. population did not exceed 
18.3% of the cancer RfD. The cancer risks from chronic exposure to 
aviglycine HCl in food and surface or ground water, therefore, were not 
unreasonable.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for aviglycine HCl 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 aviglycine HCl.
    The Agency uses the Generic Estimated Environmental Concentration 
(GENEEC) or the Pesticide Root Zone Model/Exposure Analysis Modeling 
System (PRZM/EXAMS) to estimate pesticide concentrations in surface 
water and screening concentration in ground water (SCI-GROW), which 
predicts pesticide concentrations in ground water. In general, EPA will 
use GENEEC (a Tier I model) before using PRZM/EXAMS (a Tier II 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 screen for sorting out pesticides for which it is 
unlikely that drinking water concentrations would exceed human health 
LOC.
    Since the models used are considered to be screening tools in the 
risk assessment process, the Agency does not use estimated 
environmental concentrations (EECs), which are the model estimates of a 
pesticide's concentration in water. EECs derived from these models are 
used 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 aviglycine HCl they 
are further discussed in the aggregate risk sections in Unit E.
    Based on the GENEEC and SCI-GROW models, the EECs of aviglycine HCl 
acute peak exposures are estimated to be 0.582 parts per billion (ppb) 
for surface water and 0.00028 ppb for ground water. The EECs for 
chronic 90 day exposures are estimated to be 0.0194 ppb for surface 
water and 0.00028 ppb for ground water. Acute EECs did not exceed 
DWLOCs for the subpopulation females 13-49 years of age (49.05 ppb) or 
for the general U.S. population (47.32 ppb). Acute DWLOCs were not 
calculated for other subpopulations because of a lack of relevance to 
the sensitive developmental endpoint. EECs also did not exceed DWLOCs 
for any population considered in chronic (Table 4) or cancer estimates 
(Table 5). Aggregate cancer risks and the risks from aggregate acute or 
chronic exposure to aviglycine HCl in food and surface or ground water, 
therefore, are not unreasonable.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in

[[Page 7602]]

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). Aviglycine HCl 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 FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    EPA does not have, at this time, available data to determine 
whether aviglycine HCl has a common mechanism of toxicity with other 
substances. 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 aviglycine 
HCl and any other substances and aviglycine HCl 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 
aviglycine HCl 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 OPP concerning common mechanism determinations and 
procedures for cumulating effects from substances found to have a 
common mechanism on EPA's web site 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 database on toxicity and exposure 
unless EPA determines based on reliable data 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. In 
applying this provision, EPA either retains the default value of 10X 
when reliable data do not support the choice of a different factor, or, 
if reliable data are available, EPA uses a different additional safety 
factor value based on the use of traditional uncertainty factors and/or 
special FQPA safety factors, as appropriate.
    2. Prenatal and postnatal sensitivity. EPA initially had concern 
for aviglycine HCl-induced prenatal and postnatal toxicity. This 
concern arose from 5 incidents of fetal toxicity (developmental 
malformations) that occurred at doses lower than that which induced 
maternal toxicity in rabbits (LOAEL = 0.4 mg/kg/day versus 0.7 mg/kg/
day) and from an apparent increase in the severity of effects in rat 
offspring when compared to similarly dosed adults. A Degree of Concern 
Analysis was initiated to further investigate these issues and 
determine if an additional FQPA safety factor should be applied to risk 
equations to account for differential prenatal or postnatal 
sensitivities.
    After investigation, the degree of concern was determined to be low 
for prenatal and postnatal aviglycine HCl-induced toxicity. This 
determination was justified for prenatal effects by:
    i. The observation that the same number of similar fetal 
malformations in rabbits (5) also occurred at maternally toxic doses 
(0.7 mg/kg/day);
    ii. The conclusion that 0.4 and 0.7 mg/kg/day dose differences in 
the rabbit study were more-than-likely without biological significance; 
and
    iii. The utilization of the developmental endpoint (i.e., females 
aged 13-49), an endpoint relevant to prenatal toxicity, as a means for 
risk comparison. This determination also was justified for postnatal 
effects by:
    a. The observation that toxic doses for adult rats were ultimately 
less than that for offspring (LOAEL = 2.5 versus 4.0 mg/kg/day);
    b. The observation that increased severity of effects noticed in 
rat offspring may have been due to an inexplicable total loss of three 
litters;
    c. The observation that offspring LOAELs were partially influenced 
by body weight decrements in parents; and
    d. The observation that increased prenatal or postnatal 
sensitivities were not evident in rat developmental studies.
    In summary, adequate characterization of prenatal and postnatal 
effects and the choice of a sensitive developmental endpoint for 
comparison to exposure data satisfied our concerns related to prenatal 
and postnatal effects.
    3. Conclusion. There is a complete toxicity database for aviglycine 
HCl and exposure data are complete or are estimated based on data that 
reasonably accounts for potential prenatal and postnatal exposures to 
offspring and parents. A developmental NOAEL of 0.2 mg/kg/day was 
established in a rabbit study based on fetal effects at a dose of 0.4 
mg/kg/day which was below the maternal LOAEL of 0.7 mg/kg/day. The 
maternal and developmental LOAELs were the same in the rat 
developmental study indicating no differences in susceptibility to 
aviglycine HCl toxicity. The multigeneration reproduction study also 
showed no differences in susceptibility of parents and their offspring 
(LOAEL = 2.5 mg/kg/day). All of these studies indicate that the special 
FQPA safety factor can be reduced to 1X for purposes of the current 
assessment.

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 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 water exposure (mg/kg/day) = PAD - 
(average food + residential exposure)). This allowable exposure through 
drinking water is used to calculate a DWLOC.
    A DWLOC will vary depending on the toxic endpoint, drinking water 
consumption, and body weights. Default body weights and consumption 
values as used by the EPA's Office of Water are used to calculate 
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and 
1L/10 kg (child). Default body weights and drinking water consumption 
values vary on an individual basis. This variation will be taken into 
account in more refined screening-level and quantitative drinking water 
exposure assessments. Different populations will have different DWLOCs. 
Generally, a DWLOC is calculated for each type of risk assessment used: 
Acute, short-term, intermediate-term, chronic, and cancer.
    When EECs for surface water and 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

[[Page 7603]]

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. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to 
aviglycine HCl will occupy18.25 % of the aPAD for females 13-49 years 
old. As a worst case estimate, dietary risks for the general U.S. 
population and population subgroups were also estimated using the acute 
developmental endpoint (0.002 mg/kg/day). Exposures to aviglycine HCl 
were marginally above EPA's LOC for children 1-2 years old (163%), but 
below for the general U.S. population (32.4%). The risks posed to 
children 1-2 years old represented a worst case scenario using 
toxicologic endpoints that only occurred in utero. Therefore, the 
calculated risks were demonstrative at best. In addition, there is 
potential for acute dietary exposure to aviglycine HCl in drinking 
water. After calculating DWLOCs and comparing them to the EECs for 
surface water and ground water, EPA does not expect the aggregate 
exposure to exceed 100% of the aPAD, as shown in Table 3 of this unit. 
The risks from acute aggregate exposure to aviglycine HCl in food and 
surface or ground water, therefore, are not unreasonable.

                    Table 3. --Aggregate Risk Assessment for Acute Exposure to Aviglycine HCl
----------------------------------------------------------------------------------------------------------------
                                                   Dietary                   Surface       Ground
              Population Subgroup                  Exposure      % aPAD     Water EEC    Water EEC   Acute DWLOC
                                                 (mg/kg/day)     (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
General U. S. Population1                           0.000648         32.4        0.582      0.00028        47.32
---------------------------------------------------------------------------
Females 13-49 years old                             0.000365        18.25        0.582      0.00028        49.05
---------------------------------------------------------------------------
Children 1-2 years old1                             0.003266          163
----------------------------------------------------------------------------------------------------------------
1 These exposure estimates and risk characterizations exaggerate the risk because the majority of individuals in
  the general population and in this subpopulation are not likely to be susceptible to aviglycine HCl's
  developmental effects (i.e., not likely to be pregnant).

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
aviglycine HCl from food will utilize 1.6% of the cPAD for the U.S. 
population, 10.1% of the cPAD for all infants (<1 year old), and 10.5% 
of the cPAD for children 1-2 years old, as shown in Table 4 of this 
unit. There are no uses for aviglycine HCl that result in chronic 
residential exposure to aviglycine HCl. There is potential for chronic 
dietary exposure to aviglycine HCl in drinking water. After calculating 
DWLOCs and comparing them to the EECs for surface and ground water, EPA 
does not expect the aggregate exposure to exceed 100% of the cPAD, as 
shown in Table 4 of this unit. The risks from chronic aggregate 
exposure to aviglycine HCl in food and surface or ground water, 
therefore, are not unreasonable.

            Table 4. --Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Aviglycine HCl
----------------------------------------------------------------------------------------------------------------
                                                   Dietary                   Surface       Ground
              Population Subgroup                Exposure mg/    % cPAD     Water EEC    Water EEC     Chronic
                                                    kg/day       (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                     0.000128          1.6       0.0194      0.00028        0.276
--------------------------------------------------------------
All Infants (<1 year old)                           0.000807         10.1       0.0194      0.00028
--------------------------------------------------------------
Children 1-2 years old                              0.000840         10.5       0.0194      0.00028        0.072
--------------------------------------------------------------
Children 3-5 years old                              0.000503          6.3       0.0194      0.00028
--------------------------------------------------------------
Children 6-12 years old                             0.000186          2.3       0.0194      0.00028
--------------------------------------------------------------
Youth 13-19 years old                               0.000064          0.8       0.0194      0.00028
--------------------------------------------------------------
Adults 20-49 years old                              0.000049          0.6       0.0194      0.00028
--------------------------------------------------------------
Adults 50+ years old                                0.000072          0.9       0.0194      0.00028
--------------------------------------------------------------
Females 13-49 years old                             0.000058          0.7        0.582      0.00028        0.238
----------------------------------------------------------------------------------------------------------------

    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).
    Aviglycine HCl 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 
LOC.
    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).Aviglycine HCl 
is not registered for use on any sites that would result in residential 
exposure. Therefore, the aggregate risk is the sum

[[Page 7604]]

of the risk from food and water, which do not exceed the Agency's LOC.
    5. Aggregate cancer risk for U.S. population. Using the exposure 
assumptions generated from cancer endpoints (RfD = 0.0007 mg/kg/day) 
and chronic durations of exposure, EPA has concluded that exposure to 
aviglycine HCl from food will utilize 18.3% of the cancer RfD for the 
U.S. population. There are no uses for aviglycine HCl that result in 
carcinogenic residential exposure. There is, however, the potential for 
exposure to aviglycine HCl in drinking water. After calculating a 
cancer DWLOC and comparing it to EECs for surface water and ground 
water, EPA does not expect the aggregate exposure to exceed 100% of the 
cancer RfD, as shown in Table 5 of this unit. The cancer risks from 
chronic aggregate exposure to aviglycine HCl in food and surface water 
or ground water, therefore, are not unreasonable.

                    Table 5.--Aggregate Cancer Risk Assessment for Exposure to Aviglycine HCl
----------------------------------------------------------------------------------------------------------------
                                                                Dietary                   Surface
                     Population Subgroup                      Exposure mg/ % of Cancer   Water EEC      Cancer
                                                                 kg/day        RfD         (ppb)        DWLOC
----------------------------------------------------------------------------------------------------------------
U.S. Population                                                  0.000128         18.3       0.0194        20.02
----------------------------------------------------------------------------------------------------------------

    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, and to infants and children from aggregate 
exposure to aviglycine HCl residues at the established tolerance 
levels.

IV. Other Considerations

A. Endocrine Disruptors

    Incubation with aviglycine HCl did not change reporter gene 
activity induced by estradiol (estrogen) and dihydrotestosterone 
(androgen) and inhibited by 4-hydroxytamoxifen (anti-estrogen) and 
hydroxyflutamide (anti-androgen) at non-cytotoxic doses. Aviglycine 
HCl-induced pathologies of organs associated with the endocrine system 
were not observed consistently at non-toxic doses. Aviglycine HCl, 
therefore, was qualified as a non-endocrine disrupting compound.

B. Analytical Enforcement Methodology

    Adequate enforcement methodology (high performance liquid 
chromatography-fluorescence detector) that has been EPA-validated is 
available to enforce the apple and pear tolerance expression. The 
method may be requested from: Christine Olinger, Acting Chief, 
Analytical Chemistry Branch, Environmental Science Center, 701 Mapes 
Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail 
address: [email protected].
    In addition, enforcement methodologies are available to enforce the 
stone fruits crop group 12, excepting cherries, tolerance expression. 
Preliminary review of the proposed enforcement methods for residues of 
aviglycine HCl on stone fruits crop group 12, excepting cherries, has 
indicated that they appear to be suitable for enforcement purposes. 
Given that the methods for the stone fruits crop group 12, excepting 
cherries, reflect only minor modification of the EPA-validated method, 
and that the registrant has provided the Agency with concurrent 
fortification data to demonstrate that the methods are adequate for 
data collection purposes and with an independent Laboratory Validation, 
coupled with the EPA's preliminary review, EPA concludes that the 
methods are suitable as enforcement methods to support tolerances 
associated with this action. Those methods may be requested from: 
Sheryl K. Reilly, Chief, Biochemical Pesticides Branch, Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Avenue, NW., Washington, DC 20460-0001, telephone number: (703) 308-
8269; e-mail address: [email protected].

C. International Residue Limits

    There are no Codex Alimentarius Commission (CODEX) maximum residue 
levels for residues of aviglycine HCl.

D. Conditions

    Time-limited tolerances (May 7, 1997, 62 FR 24835, FRL-5713-5 and 
July 12, 2001, 66 FR 36481, FRL-6790-7) were established for the 
biochemical pesticide aviglycine HCl in connection with conditional 
section three registrations (June 13, 1997, 62 FR 32325, FRL-5721-4). 
All tolerances were time-limited because of the existence of a rat 2-
generation reproduction study data gap. The time-limitation allowed for 
development and review of the data. Based on the available 
toxicological data, the thousandfold uncertainty factor, and the levels 
of exposure, the EPA determined at that time that there was a 
reasonable certainty that no harm would result to the U.S. population, 
including infants and children, from aggregate exposure to aviglycine 
HCl and its residues during the period of the time-limited tolerances. 
The rat 2-generation reproduction study, imposed by EPA to augment the 
results of the rat developmental toxicity study, was submitted to the 
Agency by Abbott Laboratories on September 27, 1999. It has now been 
reviewed and found by EPA to satisfy the 1997 condition of 
registration. Therefore, there currently are no data gaps associated 
with aviglycine HCl. A new database uncertainty factor applied to 
carcinogenic endpoints has now been established and is based on a 
review of submitted cancer data. This additional uncertainty factor has 
not affected current tolerance levels or crop uses. Additional cancer 
studies may be required in the future, however, should the registrant 
propose to alter tolerance levels, crop uses, application rates, pre-
harvest intervals, or other factors important to human exposure.

V. Conclusion

    Therefore, establishment of tolerances for residues of aviglycine 
HCl, in or on apple and pear at 0.08 ppm, and in or on the stone fruits 
crop group 12, excepting cherries, at 0.170 ppm, is appropriate.

VI. Objections and Hearing Requests

    Under section 408(g) of FFDCA, as amended by 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 FFDCA by FQPA, EPA 
will continue to use those procedures, with appropriate adjustments, 
until the necessary modifications can be made. The new section 408(g) 
of FFDCA provides essentially the same process for persons to 
``object'' to a regulation for an exemption from the requirement of a

[[Page 7605]]

tolerance issued by EPA under new section 408(d) of FFDCA, as was 
provided in the old sections 408 and 409 of FFDCA. However, the period 
for filing objections is now 60 days, rather than 30 days.

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0389 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before April 19, 
2004.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm.104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is 
open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Office of the Hearing Clerk is 
(703) 603-0061.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VI.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.1. Mail your 
copies, identified by docket ID number OPP-2003-0389, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit I.B.1. You may also send an electronic copy of 
your request via e-mail to: [email protected]. Please use an ASCII 
file format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. 
Do not include any CBI in your electronic copy. You may also submit an 
electronic copy of your request at many Federal Depository Libraries.

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

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

VII. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does 
not contain any information collections subject to OMB approval under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose 
any enforceable duty or contain any unfunded mandate as described under 
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 
104-4). Nor does it require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does 
not involve any technical standards that would require Agency 
consideration of voluntary consensus standards pursuant to section 
12(d) of the National Technology Transfer and Advancement Act of 1995 
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of FFDCA, such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled 
Federalism(64 FR 43255, August 10, 1999). Executive Order 13132 
requires EPA to develop an accountable process to ensure ``meaningful 
and timely input

[[Page 7606]]

by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. For these same reasons, the Agency has 
determined that this rule does not have any ``tribal implications'' as 
described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
Order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

VIII. Congressional Review Act

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

List of Subjects in 40 CFR Part 180

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

    Dated: February 5, 2004.
Sheryl K. Reilly
acting Director, Biopesticides and Pollution Prevention Division, 
Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. Section 180.502 is amended by revising the section heading and 
paragraph (a) to read as follows:


Sec. 180.502  Aminoethoxyvinylglycine hydrochloride (aviglycine HCl); 
tolerances for residues.

    (a) General. Tolerances are established for residues of 
aminoethoxyvinylglycine hydrochloride (aviglycine HCl) in or on the 
following food commodities:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Apple................................................               0.08
Fruit, stone, group 12, except cherry................              0.170
Pear.................................................               0.08
------------------------------------------------------------------------

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[FR Doc. 04-3371 Filed 2-17-04; 8:45 am]
BILLING CODE 6560-50-S