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Pyriproxyfen - Pesticide Filing Petition 3/01

ENVIRONMENTAL PROTECTION AGENCY

[PF-1006; FRL-6772-4]

Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-1006, must be
received on or before May 4, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-1006 in the subject line on the first page of your
response.

[[Page 17884]]

FOR FURTHER INFORMATION CONTACT: By mail: Sidney Jackson, Registration
Division, Minor Use Inerts and Emergency Response Branch, (7505C),
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)
305-7610; e-mail address: jackson.sidney@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                      affected  entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select "Laws and
Regulations," "Regulations and Proposed Rules," and then look up the
entry for this document under the "Federal Register--Environmental
Documents." You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for
this action under docket control number PF-1006. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-1006 in the subject line on the
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-1006. Electronic comments may
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI 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. In addition to one complete
version of the comment that includes any 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 version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under FOR FURTHER INFORMATION
CONTACT.

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

    You may find the following suggestions helpful for preparing your
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used
that support your views.
    4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set
forth in section 408(d)(2); however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
support granting of the petition. Additional data may be needed before
EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: March 20, 2001.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioners. EPA is publishing the petition summary verbatim without
editing it in any way. The petition summary announces the availability
of a description of the analytical methods available to EPA for the
detection and measurement of the pesticide chemical residues or an
explanation of why no such method is needed.

Interregional Research Project #4 (IR-4)

0E6081

    EPA has received a pesticide petition (0E6081) from the
Interregional Research Project #4 (IR-4), Technology Centre of New
Jersey, Rutgers, the State University of New Jersey, 681 U.S. Highway
#1 South, North Brunswick, NJ 08021-3390 proposing, pursuant to section
408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C.346a(d), to amend 40 CFR part 180 by establishing a tolerance for
residues of pyriproxyfen, 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy
pyridine, in or on the raw agricultural commodity pistachio at 0.02
parts per million (ppm). EPA has determined that the petition contains
data or information regarding the elements set forth in section
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
support granting of the petition. Additional data may be needed before
EPA rules on the petition.

A. Residue Chemistry

    1. Plant and animal metabolism. Metabolism of 14C-
pyriproxyfen labelled in the phenoxyphenyl ring and in the pyridyl ring
has been studied in cotton, apples, tomatoes, lactating goats, and
laying hens (and rats). The major metabolic pathways in plants is aryl
hydroxylation and cleavage of the ether linkage, followed by further
metabolism into more polar products by further oxidation and/or
conjugation reactions. However, the bulk of the radiochemical residue
on raw agricultural commodity samples remained as parent. Comparing
metabolites detected and quantified from cotton, apple, tomato, goat
and hen (and rat) shows that there are no significant aglycones in
plants which are not also present in the excreta or tissues of animals.
The residue of concern is best defined as the parent, pyriproxyfen.
    Ruminant and poultry metabolism studies demonstrated that transfer
of administered 14C-residues to tissues was low. Total
14C-residues in goat milk, muscle and tissues accounted for
less than 2% of the administered dose, and were less than 1 ppm in all
cases. In poultry, total 14C-residues in eggs, muscle and
tissues accounted for about 2.7% of the administered dose, and were
less than 1 ppm in all cases except for gizzard.
    2.  Analytical method. The gas-chromotography/nitrogen-phosphorous
specific flame ionization detector (NPD) and high-pressure liquid
chromotography/fluorescence (FLD) method RM-33N-2 is adequate for
collecting data on residues of pyriproxyfen in/on nutmeat. Adequate
method validation data have been submitted for this method and EPA has
successfully validated the analytical method for analysis of nutmeat.
The limit of quantitation (LOQ) is 0.02 ppm for residues of
pyriproxyfen in/on nutmeat.
    3. Magnitude of residues. Pyriproxyfen residue data from tree nut
field studies were used as surrogate data for pistachio. Data from six
field trials conducted in California during 1997 depicting residues of
pyriproxyfen in/on almonds were reviewed by the Agency and found to be
acceptable. Residues of pyriproxyfen were non-detectable (0.01 ppm) in/
on 12 samples of nutmeat. In the studies conducted at 2x the proposed
application rate, residues of pyriproxyfen were 0.01 ppm in/on three
samples of nutmeat, and one sample bore residues at the limit of
detection (LOD) (0.01 ppm). Data are available from four field trials
on walnuts conducted in California during 1996 Residues of pyriproxyfen
and 4'-OH-PYR were non-detectable (0.01 ppm) in/on eight walnut samples
harvested approximately 21 days after the last of three broadcast
applications of the 0.86 lb/gal EC formulation at approximately 50
grams active ingredient (ai)/acre (A)/application (0.33 pound ai/A/
season); 1x the maximum proposed seasonal rate. Residues of
pyriproxyfen in/on eight samples of walnuts treated as described above
were each less than the LOQ (0.02 ppm).

B. Toxicological Profile

    1. Acute toxicity. The acute toxicity of technical grade
pyriproxyfen is low by all routes, classified as Category III for acute
inhalation toxicity eye irritation, and Category IV for acute oral and
dermal toxicity, and skin/eye irritation. Pyriproxyfen is not a skin
sensitizing agent.
    2. Genotoxicity. Pyriproxyfen was negative in the following tests
for mutagenicity: Ames assay with and without S9 activation, in vitro
unscheduled DNA synthesis in HeLa S3 cells, in vitro gene mutation in
V79 Chinese hamster cells, and in vitro chromosomal aberration with and
without S9 activation in Chinese hamster ovary cells.
    3. Reproductive and developmental toxicity. In the rat
developmental toxicity study, maternal toxicity (decreases in food
consumption, body weight, and body weight gain with increases in water
consumption was observed at doses of 300 milligrams (mg)/kilogram (kg)/
day and greater, the no observed adverse effect level (NOAEL) for
prenatal developmental toxicity was 100 mg/kg/day with increased
incidences of skeletal variations and unspecified visceral variations
at 1,000 mg/kg/day. A rabbit teratology study resulted in a maternal
NOAEL of 100 mg/kg/day, with no developmental effects observed in the
rabbit fetuses.
    In a 2-generation reproduction toxicity study in rats, parental
toxicity (decreased body weight, weight gain and food consumption in
both sexes and both generations and increased liver weight in both
sexes of the F1 generation and liver and kidney histopathology in F1
males was observed at the highest dose tested (HDT) (5,000 ppm)
(equivalent to 386 mg/kg/day for males and 442 mg/kg/day for females
and 519 mg/kg/day for males and 554 mg/kg/day for females F1
generation.) The parental NOAEL is established at 1,000 ppm and the
reproductive NOAEL is established at 5,000 ppm.
    4. Subchronic toxicity. Subchronic oral toxicity studies conducted
with pyriproxyfen technical in the rat, mouse and dog indicate a low
level of toxicity. Effects observed at high dose levels consisted
primarily of decreased body weight gain; increased liver weights;
histopathological changes in the liver and kidney; decreased red blood
cell counts, hemoglobin and hematocrit; altered blood chemistry
parameters; and, at 5,000 and 10,000 ppm in mice, a decrease in
survival rates. The NOAELs from these studies were 400 ppm (23.5 mg/kg/
day for males, 27.7 mg/kg/day for females) in rats, 1,000 ppm (149.4
mg/kg/day for males, 196.5 mg/kg/day for females) in mice, and 100 mg/
kg/day in dogs.
    5. Chronic toxicity. Pyriproxyfen technical has been tested in
chronic studies with dogs, rats and mice. Pyriproxyfen technical was
administered to dogs in capsules at doses of 0, 30, 100, 300 and 1,000
mg/kg/day for 1-year. Dogs exposed to dose levels of 300 mg/kg/day or
higher showed decreased weight gain, increased absolute and relative
liver weight, mild anemia, increased cholesterol and triglycerides in
both sexes and slight anemia in males. The NOAEL in this study was 100
mg/kg/day. Pyriproxyfen technical was administered to mice at doses of
0, 120, 600 and 3,000 ppm in diet for 78-weeks. The NOAEL for systemic
effects in this study was 600 ppm (84 mg/kg/day in males, 109.5 mg/kg/
day in females), and a lowest observed adverse effect (LOAEL) of 3,000
ppm (420 mg/kg/day in males, 547 mg/kg/day in females) was established
based on an increase in kidney lesions.
    In a 2-year study in rats, pyriproxyfen technical was administered
in the diet at levels of 0, 120, 600, and 3,000 ppm. The NOAEL for
systemic effects in this study was 600 ppm (27.31 mg/kg/day in males,
35.1 mg/kg/day in females). A LOAEL of 3,000 ppm (138 mg/kg/day in
males, 182.7 mg/kg/day in females) was established based on a
depression in body weight gain in females.
    6. Animal metabolism. The absorption, tissue distribution,
metabolism and excretion of 14C-labeled pyriproxyfen were
studied in rats after single oral doses of 2 or 1,000 mg/kg bw
(phenoxyphenyl and pyridyl label), and after a single oral dose of 2
mg/kg bw (phenoxyphenyl label only) following 14 daily oral doses at 2
mg/kg bw of unlabelled material. For all dose groups, most (88-96%) of
the administered radiolabel was excreted in the urine and feces within
two days after radiolabeled test material dosing, and 92-98% of the
administered dose was excreted within seven days. Seven days after
dosing, tissue residues were generally low, accounting for no more than
0.3% of the dosed 14C. Radiocarbon concentrations in fat
were the highest in tissues analyzed. Recovery in tissues over time
indicates that the potential for bioaccumulation is minimal. There were
no significant sex or dose-related differences in excretion or
metabolism.
    7. Endocrine disruption. Pyriproxyfen is specifically designed to
be an insect growth regulator and is known to produce juvenoid effects
on arthropod development. However, according to Valent this mechanism-
of-action in target insects and other some arthropods has no relevance
to any mammalian endocrine system. While specific tests, uniquely
designed to evaluate the potential effects of pyriproxyfen on mammalian
endocrine systems have not been conducted, the toxicology of
pyriproxyfen has been extensively evaluated in acute, sub-chronic,
chronic, developmental, and reproductive toxicology studies including
detailed histopathology of numerous tissues. The results of these
studies show no evidence of any endocrine-mediated effects and no
pathology of the endocrine organs. Consequently, Valent concludes that
pyriproxyfen does not possess estrogenic or endocrine disrupting
properties applicable to mammals.
    8. Neurotoxicity. Neither neurotoxic symptoms nor any other
indication of neurotoxicity has been observed in any of the acute,
subchronic, chronic, developmental, or reproductive studies performed
with pyriproxyfen.
    9. Toxicological endpoints. EPA has established a reference dose
(RfD) for pyriproxyfen of 0.35 mg/kg bw/day, based on the NOAEL from
the rat 2-year chronic/carcinogenicity study and a safety factor of
100. However, the Agency has not yet identified acute or short term
toxicity endpoints of concern for oral, inhalation, or dermal exposure.
Pyriproxyfen is classified as Category E: Not carcinogenic in two
acceptable animal studies.

C. Aggregate Exposure

    1. Dietary exposure. An evaluation of chronic dietary exposure to
include drinking water has been performed for the U.S. Population and
various sub-populations including infants and children. Because no
acute dietary endpoint for pyriproxyfen residues was determined, the
Agency concludes that there is a reasonable certainty of no harm from
acute exposure from drinking water.
    i. Food. Chronic dietary exposure to pyriproxyfen residues was
calculated for the U.S. population and 26 population subgroups assuming
tolerance level residues and 100% of the crop treated. Chronic dietary
exposure was at or below 0.705 % of the reference dose. Generally
speaking, the Agency has no cause for concern if total residue
contribution for published and proposed tolerances is less than 100
percent of the RfD.
    ii. Drinking water. Since pyriproxyfen is applied outdoors to
growing agricultural crops, the potential exists for pyriproxyfen or
its metabolites to reach ground or surface water that may be used for
drinking water. Because of the physical properties of pyriproxyfen, it
is unlikely that pyriproxyfen or its metabolites can leach to potable
groundwater. To quantify potential exposure from drinking water,
surface water concentrations for pyriproxyfen were estimated using
GENEEC 1.3. The average 56-day concentration predicted in the simulated
pond water was 0.16 ppb. Using standard assumptions about body weight
and water consumption, the chronic exposure to pyriproxyfen from this
drinking water would be 4.57 x 10**-6 and 1.6 x
10**-5 mg/kg bw/day for adults and children, respectively;
0.0046 percent of the RfD (0.35 mg/kg/day) for children. Based on this
worse case analysis, Valent concludes that the contribution of water to
the dietary risk is negligible.
    2. Non-dietary exposure. Pyriproxyfen is the active ingredient in
numerous registered products for household use -- primarily for indoor,
non-food applications by consumers. The consumer uses of pyriproxyfen
typically do not involve chronic exposure. Instead, consumers are
exposed intermittently to a particular product (e.g., pet care pump
spray) containing pyriproxyfen. Since pyriproxyfen has a relatively
short elimination half-life, cumulative toxicological effects resulting
from bioaccumulation are not plausible following short-term,
intermittent exposures. Further, pyriproxyfen is short-lived in the
environment and this indoor domestic use of pyriproxyfen provides only
relatively short-term reservoirs. Thus, consumer use of these products
results in acute and short term intermittent exposures.
    No acute dermal, or inhalation dose or endpoint was identified in
the toxicity data for pyriproxyfen. Similarly, doses and endpoints were
not identified for short and intermediate term dermal or inhalation
exposure to pyriproxyfen. There are reasonable certainties of no harm
from acute, short term, and intermediate term dermal and inhalation
occupational and residential exposures due to the lack of significant
toxicological effects observed. Thus, no detailed exposure and risk
analyses for non-dietary exposures to pyriproxyfen are necessary.

D. Cumulative Effects

    According to Valent there are no other pesticidal compounds that
are structurally related to pyriproxyfen and have similar effects on
animals. In consideration of potential cumulative effects of
pyriproxyfen and other substances that may have a common mechanism of
toxicity, there are currently no available data or other reliable
information indicating that any toxic effects produced by pyriproxyfen
would be cumulative with those of other chemical compounds. Thus, only
the potential risks of pyriproxyfen have been considered in this
assessment of aggregate exposure and effects. Valent will submit
information for EPA to consider concerning potential cumulative effects
of pyriproxyfen consistent with the schedule established by EPA at 62
Federal Register 42020 (August 4, 1997) and other subsequent EPA
publications pursuant to the Food Quality Protection Act.

E. Safety Determination

    1. U.S. population--i. Chronic dietary exposure and risk. Using the
Tier I dietary exposure assessment, calculated chronic dietary exposure
resulting from residue exposure from existing and proposed uses of
pyriproxyfen is minimal. The estimated chronic dietary exposure from
food for the overall U.S. Population and many non-child/infant
subgroups is from 0.000338 to 0.000652 mg/kg bw/day, 0.097 to 0.186 per
cent of the RfD. Addition of the small but worse case potential chronic
exposure from drinking water (calculated above) increases exposure by
only 4.57 x 10**-6 mg/kg bw/day and does not change the
maximum occupancy of the RfD significantly. Generally, the Agency has
no cause for concern if total residue contribution is less than 100
percent of the RfD. It can be concluded that there is a reasonable
certainty that no harm will result to the overall U.S. Population and
infants and children from aggregate, chronic exposure to pyriproxyfen
residues.
    ii.  Acute dietary exposure and risk. An acute dietary dose and
endpoint was not identified. Thus, the risk from acute aggregate
exposure is considered to be negligible.
    iii. Non-dietary exposure and aggregate risk. Acute, short term,
and intermediate term dermal and inhalation risk assessments for
residential exposure are not required due to the lack of significant
toxicological effects observed.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of pyriproxyfen, FFDCA
section 408 provides that EPA shall apply an additional margin of
safety, up to ten-fold, for added protection for infants and children
in the case of threshold effects unless EPA determines that a different
margin of safety will be safe for infants and children.
    The toxicological data base for evaluating pre- and post-natal
toxicity for pyriproxyfen is complete with respect to current data
requirements. There are no special pre- or post-natal toxicity concerns
for infants and children, based on the results of the rat and rabbit
developmental toxicity studies or the 2-generation reproductive
toxicity study in rats. Valent concludes that reliable data support use
of the standard 100-fold uncertainty factor and that an additional
uncertainty factor is not needed for pyriproxyfen to be further
protective of infants and children.

F. International Tolerances

    There are no Codex MRLs for pyriproxyfen.
[FR Doc. 01-8140 Filed 4-3-01;8:45 am]