[Federal Register: December 22, 2004 (Volume 69, Number 245)]
[Notices]
[Page 76724-76729]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22de04-45]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0403; FRL-7689-6]
Pyriproxyfen: 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 identification (ID) number OPP-
2004-0403, must be received on or before January 21, 2005.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.
FOR FURTHER INFORMATION CONTACT: Joseph Tavano, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6411; e-mail address: tavano.joseph@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you 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 ID number OPP-2004-0403. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The docket telephone number is (703) 305-
5805.
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/.
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.
Certain types of information will not be placed in the EPA Dockets.
Information claimed as CBI and other information whose disclosure is
restricted by statute, which is not included in the official public
docket, will not be available for public viewing in EPA's electronic
public docket. EPA's policy is that copyrighted material will not be
placed in EPA's electronic public docket but will be available only in
printed, paper form in the official public docket. To the extent
feasible, publicly available docket materials will be made available in
EPA's electronic public docket. When a document is selected from the
index list in EPA Dockets, the system will identify whether the
document is available for viewing in EPA's electronic public docket.
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. EPA intends to work towards
providing electronic access to all of the publicly available docket
materials through EPA's electronic public docket.
For public commenters, it is important to note that EPA's policy is
that public comments, whether submitted electronically or in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that
[[Page 76725]]
is otherwise protected by statute, please follow the instructions in
Unit I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/
, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2004-0403. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov,
Attention: Docket ID number OPP-2004-0403. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID number OPP-2004-0403.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
number OPP-2004-0403. Such deliveries are only accepted during the
docket's normal hours of operation as identified in Unit I.B.1.
D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is 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 docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior notice. If you have any
questions about CBI or the procedures for claiming CBI, please consult
the person listed 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
ID number as signed 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 Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in FFDCA 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: December 9, 2004.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by the petitioner and represents the view of the petitioner.
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.
Valent U.S.A. Corporation
PP 4F6847
EPA has received a pesticide petition 4F6847 from Valent U.S.A.
Corporation, 1600 Riviera Ave., Suite 200, Walnut
[[Page 76726]]
Creek, California 94596-8025 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 tolerances for residues of
pyriproxyfen, 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine (CA), in
or on the raw agricultural commodities (RAC) grass forage and hay (crop
group 17). 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 supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
A. Residue Chemistry
1. Plant metabolism. Metabolism of 14C-pyriproxyfen
labeled 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 radio-chemical residue
on RAC samples remained as parent. Comparing metabolites detected and
quantified from cotton, apple, tomato, goat and hen (and rat) shows
that there are no significant metabolites in plants which are not also
present in the excreta or tissues of animals. Therefore, 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 part per
million (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. Practical analytical methods for detecting
and measuring levels of pyriproxyfen (and relevant metabolites) have
been developed and validated in/on all appropriate agricultural
commodities, respective processing fractions, milk, animal tissues, and
environmental samples. The extraction methodology has been validated
using aged radio-chemical residue samples from metabolism studies. The
methods have been validated in cotton seed, apples, soil, and oranges
at independent laboratories. EPA has successfully validated the
analytical methods for analysis of cotton seed, pome fruit, nutmeats,
almond hulls, and fruiting vegetables. The limit of detection of
pyriproxyfen in the methods is 0.01 ppm which will allow monitoring of
food with residues at the levels proposed for the tolerances.
3. Magnitude of residues--i. Grass, forage, fodder, and hay. Twelve
field trials in grass were conducted in 2002 and 2003. The analytical
data show that the average measured residue in/on grass forage samples
was 0.05 ppm (n = 24, [sigma]n-1 = 0.10 ppm) pyriproxyfen. Similarly,
the analytical data show that the average measured residue in/on grass
hay samples was 0.10 ppm (n = 24, [sigma]n-1 = 0.19 ppm). These data
support a proposed tolerance for pyriproxyfen in/on grass forage of 0.5
ppm and grass hay of 1.0 ppm.
ii. Secondary residues. The proposed new use on grass represents an
additional feed commodity. Using established and proposed tolerances to
calculate the maximum feed exposure to feed animals, and using the very
low potential for residue transfer demonstrated in the milk cow feeding
residue study, detectable secondary residues in animal tissues, milk,
and eggs are not expected. Therefore, no tolerances are required for
these commodities.
iii. Rotational crops. The results of a confined rotational crops
accumulation study indicate that no rotational crop planting
restrictions or rotational crop tolerances are required.
B. Toxicological Profile
1. Acute toxicity. The acute toxicity of technical grade
pyriproxyfen is low by all routes. The compound is classified as
Category III for acute dermal and inhalation toxicity, and Category IV
for acute oral toxicity, and skin/eye irritation. Pyriproxyfen is not a
skin sensitizing agent.
2. Genotoxicity. Pyriproxyfen does not present a genetic hazard.
Pyriproxyfen was negative in the following tests for mutagenicity: Ames
assay with and without S9, 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 in Chinese hamster
ovary cells.
3. Reproductive and developmental toxicity. Pyriproxyfen is not a
developmental or reproductive toxicant. Developmental toxicity studies
have been performed in rats and rabbits, and multigenerational effects
on reproduction were tested in rats. These studies have been reviewed
and found to be acceptable to the Agency.
In the developmental toxicity study conducted with rats, technical
pyriproxyfen was administered by gavage at levels of 0, 100, 300, and
1,000 milligrams/kilogram/bodyweight day (mg/kg/bwt day) during
gestation days 7-17. Maternal toxicity (mortality, decreased bwt gain
and food consumption, and clinical signs of toxicity) was observed at
doses of 300 mg/kg/bwt day and greater. The maternal no observed
adverse effect level (NOAEL) was 100 mg/kg/bwt day. A transient
increase in skeletal variations was observed in rat fetuses from
females exposed to 300 mg/kg/bwt day and greater. These effects were
not present in animals examined at the end of the postnatal period,
therefore, the NOAEL for prenatal developmental toxicity was 100 mg/kg/
bwt day. An increased incidence of visceral and skeletal variations was
observed postnatally at 1,000 mg/kg/bwt day. The NOAEL for postnatal
developmental toxicity was 300 mg/kg/bwt day.
In the developmental toxicity study conducted with rabbits,
technical pyriproxyfen was administered by gavage at levels of 0, 100,
300, and 1,000 mg/kg/bwt day during gestation days 6-18. Maternal
toxicity (clinical signs of toxicity including one death, decreased bwt
gain and food consumption, and abortions or premature deliveries) was
observed at oral doses of 300 mg/kg/bwt day or higher. The maternal
NOAEL was 100 mg/kg/bwt day. No developmental effects were observed in
the rabbit fetuses. The NOAEL for developmental toxicity in rabbits was
1,000 mg/kg/bwt day.
In the rat reproduction study, pyriproxyfen was administered in the
diet at levels of 0, 200, 1,000, and 5,000 ppm through two generations
of rats. Adult systemic toxicity (reduced bwts, liver and kidney
histopathology, and increased liver weight) was produced at the 5,000
ppm dose (453 mg/kg/bwt day in males, 498 mg/kg/bwt day in females)
during the pre-mating period. The systemic NOAEL was 1,000 ppm (87 mg/
kg/bwt day in males, 96 mg/kg/bwt day in females). No effects on
reproduction were produced at 5,000 ppm, the higest dose tested (HDT).
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 bwt gain; increased liver weights;
histopathological changes in the liver and kidney; decreased red blood
cell counts, hemoglobin and hematocrit;
[[Page 76727]]
altered blood chemistry parameters; and, at 5,000 and 10,000 ppm in
mice, adecrease in survival rates. The NOAELs from these studies were
400 ppm (23.5 mg/kg/bwt day for males, 27.7 mg/kg/bwt day for females)
in rats, 1,000 ppm (149.4 mg/kg/bwt day for males, 196.5 mg/kg/bwt day
for females) in mice, and 100 mg/kg/bwt day in dogs. In a four week
inhalation study of pyriproxyfen technical in rats, decreased bwt and
increased water consumption were observed at 1,000 mg/m3.
The NOAEL in this study was 482 mg/m3.
A 21-day dermal toxicity study in rats with pyriproxyfen technical
did not produce any signs of dermal or systemic toxicity at 1,000 mg/
kg/bwt day, the HDT. In a 21-day dermal study conducted with
KNACK[reg]. Insect Growth Regulator, the test material produced a NOAEL
of 1,000 mg/kg/bwt day HDT for systemic effects, and a NOAEL for skin
irritation of 100 mg/kg/bwt day.
5. Chronic toxicity. Pyriproxyfen technical has been tested in
chronic studies with dogs, rats, and mice. EPA has established a
reference dose (RfD) for pyriproxyfen of 0.35 mg/kg/bwt day, based on
the NOAEL in female rats from the 2-year chronic/oncogenicity study.
Effects cited by EPA in the RfD Tracking Report include negative trend
in mean red blood cell volume, increased hepatocyte cytoplasm and
cytoplasm: Nucleus ratios, and decreased sinusoidal spaces.
Pyriproxyfen is not a carcinogen. Studies with pyriproxyfen have
shown that repeated high dose exposures produced changes in the liver,
kidney, and red blood cells, but did not produce cancerin test animals.
No oncogenic response was observed in a rat 2-year chronic feeding/
oncogenicity study or in a seventy-eight week study on mice. The
oncogenicity classification of pyriproxyfen is ``E'' (no evidence of
carcinogenicity for humans).
Pyriproxyfen technical was administered to dogs in capsules at
doses of 0, 30, 100, 300, and 1,000 mg/kg/bwt day for 1-year. Dogs
exposed to dose levels of 300 mg/kg/bwt day or higher showed overt
clinical signs of toxicity, elevated levels of blood enzymes and liver
damage. The NOAEL in this study was 100 mg/kg/bwt 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/bwt day in males, 109.5 mg/kg/bwt
day in females), and a LOAEL of 3,000 ppm (420 mg/kg/bwt day in males,
547 mg/kg/bwt 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/bwt day in
males, 35.1 mg/kg/bwt day in females). A lowest observed adverse effect
level (LOAEL) of 3,000 ppm (138 mg/kg/bwt day inmales, 182.7 mg/kg/bwt
day in females) was established based on a depression in bwt 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/bwt
(phenoxyphenyl and pyridyl label), and after a single oral dose of 2
mg/kg/bwt (phenoxyphenyl label only) following 14 daily oral doses at 2
mg/kg/bwt of unlabelled material. For all dose groups, most (88-96%) of
the administered radio-label was excreted in the urine and feces within
2-days after radio- labeled test material dosing, and 92-98% of the
administered dose was excreted within 7-days. Seven-days after dosing,
tissue residues were generally low, accounting for no more than 0.3% of
the dosed 14C. Radio-carbon concentrations in fat were the
higher than in other 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. Metabolite toxicology. Metabolism studies of pyriproxyfen in
rats, goats, and hens, as well as the fish bioaccumulation study
demonstrate that the parent is very rapidly metabolized and eliminated.
In the rat, most (88-96%) of the administered radiolabel was excreted
in the urine and feces within 2-days of dosing, and 92-98% of the
administered dose was excreted within 7-days. Tissue residues were low
7-days after dosing, accounting for no more than 0.3% of the dosed
14C. Because parent and metabolites are not retained in the
body, the potentil for acute toxicity from in situ formed metabolites
is low. The potential for chronic toxicity is adequately tested by
chronic exposure to the parent at the maximum tolerance dose and
consequent chronic exposure to the internally formed metabolites.
Seven metabolites of pyriproxyfen, 4'-OH-pyriproxyfen, 5'3'-OH-
pyriproxyfen, desphenyl-pyriproxyfen, POPA, PYPAC, 2-OH-pyridine and
2,5-diOH-pyridine, have been tested for mutagenicity (Ames) and acute
oral toxicity to mice. All seven metabolites were tested in the Ames
assay with and without S9 at doses up to 5,000 micro-grams per plate or
up to the growth inhibitory dose. The metabolites did not induce any
significant increases in revertant colonies in any of the test strains.
Positive control chemicals showed marked increases in revertant
colonies. The acute toxicity to mice of 4'-OH-pyriproxyfen, 5'3'-OH-
pyriproxyfen, desphenyl-pyriproxyfen, POPA, and PYPAC did not appear to
markedly differ from pyriproxyfen, with all metabolites having acute
oral LD50 values greater than 2,000 mg/kg/bwt. The two
pyridines, 2-OH-pyridine and 2,5-diOH-pyridine, gave acute oral
LD50 values of 124 (male), and 166 (female) mg/kg/bwt, and
1,105 (male) and 1,000 (female) mg/kg/bwt, respectively.
8. Endocrine disruption. Pyriproxyfen is specifically designed to
be an insect growth regulator and is known to produce juvenoid effects
on arthropod development. However, 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, it is concluded that pyriproxyfen does not
possess estrogenic or endocrine disrupting properties applicable to
mammals.
C. Aggregate Exposure
1. Dietary exposure. An evaluation of chronic dietary exposure to
including both food and drinking water has been performed for the U.S.
population and various sub-populations including infants and children.
No acute dietary endpoint and dose was identified in the toxicology
data base for pyriproxyfen, therefore, the Agency has concluded that
there is a reasonable certainty of no harm from acute dietary exposure.
i. Food. Chronic dietary exposure to pyriproxyfen residues was
calculated for the U.S.population and 16 population subgroups assuming
tolerance level residues, processing factors from residue studies, and
100 percent of the crop treated (PCT). The analyses included residue
data for all existing uses, pending uses, and proposed new uses. The
results from
[[Page 76728]]
several representative subgroups are listed below. Chronic exposure to
the overall U.S. population is estimated to be 0.0008 mg/kg/bwt day,
representing 0.24% of the RfD. For the most highly exposed sub-
population, children 1 to 2 years of age, exposure is calculated to be
0.0009 mg/kg/bwt day, or 0.26% of the RfD in the following Table 1.
Generally speaking, the Agency has no cause for concern if total
residue contribution for established and proposed tolerances is less
than 100% of the RfD.
Table 1.--Calculated Chronic Dietary Exposures to the Total U.S. Population and Selected Sub-Populations to Pyriproxyfen Residues in Food
--------------------------------------------------------------------------------------------------------------------------------------------------------
Population Subgroup Exposure (mg/kg/bwt day) Percent of RfD
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total U.S. population 0.00083 0.24
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1-2 years) 0.00091 0.26
--------------------------------------------------------------------------------------------------------------------------------------------------------
Non-nursing infants(< 1 year old) 0.00049 0.14
--------------------------------------------------------------------------------------------------------------------------------------------------------
All infants (< 1 year old) 0.00051 0.15
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (6-12 years) 0.00044 0.13
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13-49 years) 0.00042 0.12
--------------------------------------------------------------------------------------------------------------------------------------------------------
Nursing Infants (< 1 year old) 0.00023 0.07
--------------------------------------------------------------------------------------------------------------------------------------------------------
ii. Drinking water. Since pyriproxyfen is applied outdoors to
growing agricultural crops, the potential exists for pyriproxyfen or
its metabolites to reach ground surface 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 ground water. To quantify potential exposure from
drinking water, surface water concentrations for pyriproxyfen were
estimated using generic expected environmental concentration (GENEEC).
The peak predicted concentration in drinking water was 0.86 part per
billion (ppb). Using standard assumptions about bwt and water
consumption, the chronic exposure to pyriproxyfen from this drinking
water would be 0.00009 mg/kg/day for infants, the most sensitive
subpopulation. This represents 0.025% of the RfD (0.35 mg/kg/day) for
infants. Based on this worse case analysis, the contribution of water
to the dietary risk is negligible.
2. Non-dietary exposure. Pyriproxyfen is currently registered for
use on residential non-food sites. Pyriproxyfen is the active
ingredient (a.i.) in numerous registered products for flea and tick
control. Formulations include foggers, aerosol sprays, emulsifiable
concentrates, and impregnated materials (pet collars). With the
exception of the pet collar uses, consumer use of pyriproxyfen
typically 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. The Agency has concluded that 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.
Chronic residential post-application exposure and risk assessments
were conducted to estimate the potential risks from pet collar uses.
The risk assessment was conducted using the following assumptions:
Application rate of 0.58 mg/a.i. day (product label), average bwt for a
1-6 year old child of 10 kg, the a.i. dissipates uniformly through 365
days (the label instruct to change collar once a year), 1% of the a.i.
is available for dermal and inhalation exposure per day (assumption
from Draft EPA Standard Operating Procedures (SOPs) for Residential
Exposure Assessments, December 18, 1997). The assessment also assumes
an absorption rate of 100%. This is a conservative assumption since the
dermal absorption was estimated to be 10%. The estimated chronic term
margin of exposure (MOE) was 61,000 for children, and 430,000 for
adults. The risk estimates indicate that potential risks from pet
collar uses do not exceed the Agency's level of concern.
D. Cumulative Effects
Section 408(b)(2)(D)(v) requires that the Agency must consider
``available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments. For
most pesticides, although the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity
in a meaningful way.
There are no other pesticidal compounds that are structurally
related
[[Page 76729]]
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 Federal Register of August 4, 1997 (62 FR
42020) (FRL-5734-6) and other subsequent EPA publications pursuant to
the Food Quality Protection Act(FQPA).
E. Safety Determination
1. U.S. population--i. Chronic dietary exposure and risk s adult
sub-populations. The results of the chronic dietary exposure assessment
described above demonstrate that estimates of chronic dietary exposure
for all existing, pending and proposed uses of pyriproxyfen are well
below the chronic RfD of 0.35 mg/kg/bwt day. The estimated chronic
dietary exposure from food for the overall U.S. population and many
non-child/infant subgroups is from 0.00014 to 0.00042 mg/kg/bwt day,
0.04 to 0.12% of the RfD. Addition of the small but worse case
potential chronic exposure from drinking water (calculated above)
increases exposure by only 0.00002 mg/kg/bwt 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% of the RfD. It can be concluded that there is a reasonable
certainty that no harm will result to the overall U.S. population or
any non-child/infant subgroups from aggregate, chronic dietary exposure
to pyriproxyfen residues.
ii. Acute dietary exposure and risk s adult sub-populations. No
acute dietary endpoint and dose were identified in the toxicology data
base for pyriproxyfen; therefore, it can be concluded that there is a
reasonable certainty that no harm will result to the overall U.S.
Population or any non-child/infant subgroups from aggregate, acute
dietary exposure to pyriproxyfen residues.
iii. Non-dietary exposure and aggregate risk s adult sub-
populations. 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. The
results of a chronic residential post-application exposure and risk
assessment for pet collar uses demonstrate that potential risks from
pet collar uses do not exceed the Agency's level of concern. The
estimated chronic term MOE for adults was 430,000.
2. Infants and children--i. Safety factor for 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 prenatal and postnatal
toxicity for pyriproxyfen is complete with respect to current data
requirements. There are no special prenatal or postnatal 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.
ii. Chronic dietary exposure and risks infants and children. Using
the conservative exposure assumptions described above, the percentage
of the RfD that will be utilized by chronic dietary (food only)
exposure to residues of pyriproxyfen ranges from 0.00023 mg/kg/bwt day
for nursing infants, up to 0.00091 mg/kg/bwt day for children (1 to 2
years of age), 0.07 to 0.26% of the RfD, respectively. Adding the worse
case potential incremental exposure to infants and children from
pyriproxyfen in drinking water (0.00009 mg/kg/bwt day) does not
materially increase the aggregate, chronic dietary exposure and only
increases the occupancy of the RfD by 0.009% to 0.010% for children (1
to 2 years of age). EPA generally has no concern for exposures below
100% of the RfD because the RfD represents the level at or below which
daily aggregate dietary exposure over a lifetime will not pose
appreciable risks to human health. It can be concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate, chronic dietary exposure to pyriproxyfen residues.
iii. Acute dietary exposure and risk s infants and children.No
acute dietary endpoint and dose were identified in the toxicology data
base for pyriproxyfen; therefore, it can be concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate, acute dietary exposure to pyriproxyfen residues.
iv. Non-dietary exposure and aggregate risk s infants and children.
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. The results of a chronic
residential post-application exposure and risk assessment for pet
collar uses demonstrate that potential risks from pet collar uses do
not exceed the Agency's level of concern. The estimated chronic term
MOE for children was 61,000.
F. International Tolerances
There are no presently existing Codex MRLs for pyriproxyfen.
[FR Doc. 04-27769 Filed 12-21-04; 8:45 am]
BILLING CODE 6560-50-S