Pyriproxyfen; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food, 48413-48417 [05-16301]
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Federal Register / Vol. 70, No. 158 / Wednesday, August 17, 2005 / Notices
withdrawal of the request for
cancellation will apply only to the
applicable FIFRA section 6(f)(1) request
listed in this notice. If the product(s)
have been subject to a previous
cancellation action, the effective date of
cancellation and all other provisions of
any earlier cancellation action are
controlling. The withdrawal request
must also include a commitment to pay
any reregistration fees due, and to fulfill
any applicable unsatisfied data
requirements.
V. Provisions for Disposition of Existing
Stocks
The effective date of cancellation will
be the date of the cancellation order.
The orders effecting these requested
cancellations will generally permit a
registrant to sell or distribute existing
stocks for 1 year after the date the
cancellation request was received. This
policy is in accordance with the
Agency’s statement of policy as
prescribed in the Federal Register of
June 26, 1991 (56 FR 29362) (FRL–
3846–4). Exceptions to this general rule
will be made if a product poses a risk
concern, or is in noncompliance with
reregistration requirements, or is subject
to a data call-in. In all cases, productspecific disposition dates will be given
in the cancellation orders.
Existing stocks are those stocks of
registered pesticide products which are
currently in the United States and
which have been packaged, labeled, and
released for shipment prior to the
effective date of the cancellation action.
Unless the provisions of an earlier order
apply, existing stocks already in the
hands of dealers or users can be
distributed, sold, or used legally until
they are exhausted, provided that such
further sale and use comply with the
EPA-approved label and labeling of the
affected product. Exception to these
general rules will be made in specific
cases when more stringent restrictions
on sale, distribution, or use of the
products or their ingredients have
already been imposed, as in a Special
Review action, or where the Agency has
identified significant potential risk
concerns associated with a particular
chemical.
List of Subjects
Environmental protection, Pesticides
and pests.
Dated: August 3, 2005.
Arnold E. Layne,
Director, Information Technology and
Resource Management Division, Office of
Pesticide Programs.
[FR Doc. 05–16194 Filed 8–16–05; 8:45 am]
BILLING CODE 6560–50–S
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ENVIRONMENTAL PROTECTION
AGENCY
[OPP–2005–0234; FRL–7732–1]
Pyriproxyfen; Notice of Filing a
Pesticide Petition to Establish a
Tolerance for a Certain Pesticide
Chemical in or on Food
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
SUMMARY: This notice announces the
initial filing of pesticide petitions
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–2005–
0234, must be received on or before
September 16, 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:
Barbara Madden, Registration Division
(7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 305–6463; e-mail address:
madden.barbara@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by
this action if you are an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS code
111)
• Animal production (NAICS code
112)
• Food manufacturing (NAICS code
311)
• Pesticide manufacturing (NAICS
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
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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–2005–
0234. 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
https://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 https://www.epa.gov/edocket/
to submit or view public comments, to
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
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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.1. 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 on 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
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 email address or other contact
information in the body of your
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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 https://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–2005–0234. 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–
2005–0234. 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,
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DC 20460–0001, Attention: Docket ID
number OPP–2005–0234.
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–2005–0234. 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.
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7. To ensure proper receipt by EPA,
be sure to identify the docket ID 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 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: August 11, 2005.
Lois Rossi,
Director, Registration Division, Office of
Pesticide Programs.
Summary of Petitions
The petitioner’s summary of the
pesticide petitions is printed below as
required by FFDCA section 408(d)(3).
The summary of the petitions was
prepared by Interregional Research
Project Number 4 (IR-4), and represents
the view of the petitioner. The petion
summary announces the availabilty 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
PP 3E6582, PP 3E6596, PP 3E6750, PP
4E6865, PP 4E6866
EPA has received pesticide petitions
(PP) 3E6582, 3E6596, 3E6750, 4E6865,
and 4E6866 from the Interregional
Research Project Number 4 IR-4,
Technology Center of New Jersey,
Rutgers, the State University of New
Jersey, 681 U.S. Highway #1 S., North
Brunswick, NJ 08902–3390 proposing,
pursuant to section 408(d) of the
FFDCA, 21 U.S.C. 346a(d), to amend 40
CFR part 180 by establishing tolerances
for residues of pyriproxyfen, 2-[1methyl-2-(4-phenoxyphenoxy)
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ethoxy]pyridine, in or on raw
agricultural commodities as follows:
1. PP 3E6582 proposes a tolerance for
white sapote and Ugli fruit at 0.3 parts
per million (ppm).
2. PP 3E6596 proposes a tolerance for
legume vegetables, crop subgroups 6a,
6b, and 6c at 0.2 ppm.
3. PP 3E6750 proposes a tolerance for
onion, dry bulb at 0.05 ppm.
4. PP 4E6865 proposes a tolerance for
strawberry at 0.3 ppm.
5. PP 4E6866 proposes a tolerance for
grape at 2.5 ppm and raisin at 4.0 ppm.
EPA has determined that the petitions
contain 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
petitions. Additional data may be
needed before EPA rules on the
petitions.
A. Residue Chemistry
1. Plant and animal metabolism.
Metabolism of 14C-pyriproxyfen labeled
in the phenoxyphenyl ring and in the
pyridyl ring has been studied in cotton,
apples, tomatoes, lactating goats, 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 commodities
(RAC) samples remained as parent.
Comparing metabolites detected and
quantified from cotton, apple, tomato,
goat, 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 part per million (ppm)
in all cases. In poultry, total 14Cresidues 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 or on all
appropriate agricultural commodities,
respective processing fractions, milk,
animal tissues, and environmental
samples. The extraction methodology
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has been validated using aged
radiochemical residue samples from
metabolism studies. The methods have
been validated in cottonseed, apples,
soil, and oranges at independent
laboratories. EPA has successfully
validated the analytical methods for
analysis of cottonseed, 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. Residue
data were generated with pyriproxyfen
for tolerance setting and dietary
exposure estimates. Adequate residue
trials were performed with pyriproxyfen
to support the uses described in this
notice of filing.
B. Toxicological Profile
An assessment of toxic effects caused
by pyriproxyfen is discussed in Unit
III.A. and Unit III.B. of the Federal
Register of April 4, 2001, (66 FR 17883)
(FRL–6772–4).
1. 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
milligrams/kilograms body weight (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 unlabeled material. For all
dose groups, most (–96%) of the
administered radiolabel was excreted in
the urine and feces within 2 days after
radiolabeled 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. Radiocarbon
concentrations in fat were 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.
2. 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
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in the body, the potential 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 tolerated
dose (MTD) and consequent chronic
exposure to the internally formed
metabolites.
Seven metabolites of pyriproxyfen, 4’OH-pyriproxyfen, 5’-OH-pyriproxyfen,
desphenyl-pyriproxyfen, POPA, PYPAC,
2-OH-pyridine and 2,5-diOH-pyridine,
have been tested for mutagenicity, via
Ames Assay, 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 revertible
colonies in any of the test strains.
Positive control chemicals showed
marked increases in reverting colonies.
The acute toxicity to mice of 4’-OHpyriproxyfen, 5’-OH-pyriproxyfen,
desphenyl-pyriproxyfen, POPA, and
PYPAC did not appear to markedly
differ from pyriproxyfen, with all
metabolites having acute oral lethal
dose (LD50) values greater than 2,000
mg/kg bwt. The two pyridines, 2-OHpyridine 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.
3. 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 some other 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 including both
food and drinking water has been
performed for the U.S. population and
various sub-populations including
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infants and children. No acute dietary
endpoint and dose was identified in the
toxicology data base for pyriproxyfen;
therefore, Valent Corporation concludes
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
assuming 100% of the crop will be
treated with pyriproxyfen. The analyses
included residue data for all existing
uses, pending uses, and proposed new
uses. The results from several
representative subgroups are listed
below. Chronic dietary exposure to the
overall U.S. population is estimated to
be 0.0238 mg/kg bwt/day, representing
6.8% of the reference dose (RfD). For the
most highly exposed sub-population,
infants, <1 years of age, dietary exposure
is calculated to be 0.0245 mg/kg bwt/
day, or 7.0% of the RfD. 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.
ii. Drinking water. Since pyriproxyfen
is applied outdoors to growing
agricultural crops, the potential exists
for pyriproxyfen or its metabolites to
reach ground water 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 residue levels in drinking water are
the peak chronic residue level as
estimated by GENEEC. Using standard
assumptions about body weight and
water consumption, the chronic
exposure to pyriproxyfen from this
drinking water would be 0.00009 mg/kg
bwt/day for adults and ‘‘0’’ year infants,
and represent 0.025% of the RfD (0.35
mg/kg/day). 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 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.
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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-term and intermediate-term
dermal or inhalation exposure to
pyriproxyfen. The Agency has
concluded that there are reasonable
certainties of no harm from acute, shortterm, 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 active ingredient (a.i.)/day,
average body weight for a 1–6 year old
child of 10 kg, the a.i. dissipates
uniformly through 365 days (the label
instructs to change the collar once a
year), 1% of the active ingredient 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 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
to pyriproxyfen and have similar effects
on animals. In consideration of potential
E:\FR\FM\17AUN1.SGM
17AUN1
Federal Register / Vol. 70, No. 158 / Wednesday, August 17, 2005 / Notices
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.
E. Safety Determination
1. U.S. population—i. Chronic dietary
exposure and risk to adult subpopulations. 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/day. The estimated
chronic dietary exposure from food for
the overall U.S. population and many
non-child/infant subgroups is from
0.006 to 0.0245 mg/kg bwt/day, 1.7 to
7.0% 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 to
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 nonchild/infant subgroups from aggregate,
acute dietary exposure to pyriproxyfen
residues.
iii. Non-dietary exposure and
aggregate risk to adult sub-populations.
Acute, short-term, and intermediateterm 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 margin of
exposure (MOE) for adults was 5,700.
VerDate jul<14>2003
13:34 Aug 16, 2005
Jkt 205001
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 10-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-natal and post-natal
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 2generation reproductive toxicity study
in rats. Valent concludes that reliable
data support use of the standard 100fold 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 risk
to 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 0.013 mg/
kg bwt/day children 6–12 years old, up
to 0.0245 mg/kg bwt/day for infants (0
years of age), 3.8 and 7.0% of the RfD,
respectively. Adding the worse case
potential incremental exposure to
infants from pyriproxyfen in drinking
water (0.9 x 10-4 mg/kg bwt/day) does
not materially increase the aggregate,
chronic dietary exposure and only
increases the occupancy of the RfD by
0.009%. 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.
Valent concludes 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
infants and children. No acute dietary
endpoint and dose were identified in
the toxicology data base for
pyriproxyfen; therefore, Valent believes
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 infants and children.
Acute, short-term, and intermediateterm dermal and inhalation risk
PO 00000
Frm 00049
Fmt 4703
Sfmt 4703
48417
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 1,425.
F. International Tolerances
There are presently no existing Codex
maximum residue levels for
pyriproxyfen.
FR Doc. 05–16301 Filed 8–16–05; 8:45 a.m.]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
[OEI–2005–2006; FRL–7951–5]
Office of Environmental Information;
Announcement of Comment Period for
Environmental Sampling, Analysis and
Results Draft Data Standards
Environmental Protection
Agency.
ACTION: Notice of Data Availability &
Comment Period.
AGENCY:
SUMMARY: Notice of availability for
public review for a 90 day comment
period is hereby given for the Draft
Environmental Sampling, Analysis and
Results (ESAR) Data Standards.
The Draft Environmental Sampling,
Analysis, and Results Data Standards
are a collection of 14 standards that are
based on the business processes used to
collect and analyze environmental data.
The collection is comprised of an
Overview, four primary standards and
nine supporting components. The
fourteen ESAR data standards are
designed to provide implementation
flexibility and improve the exchange of
environmental data across the nation.
States and U.S. EPA completed a
technical review of these data standards
in the Spring of 2004. That review lead
to the formation of Air, Waste, and
Water teams, which reviewed the
comments and produced this final
collection of draft data standard
documents. Reviewers will see that the
standards may not use the specific
terminology for a given environmental
program. In order to make the standards
work for the broadest audience, terms
were specifically chosen for relevance to
the broadest audience. Similarly, the
standards do not address all details of
each environmental program. These
standards, when final, are intended to
serve as a foundation for information
E:\FR\FM\17AUN1.SGM
17AUN1
Agencies
[Federal Register Volume 70, Number 158 (Wednesday, August 17, 2005)]
[Notices]
[Pages 48413-48417]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-16301]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0234; FRL-7732-1]
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.
-----------------------------------------------------------------------
SUMMARY: This notice announces the initial filing of pesticide
petitions 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-
2005-0234, must be received on or before September 16, 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: Barbara Madden, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6463; e-mail address: madden.barbara@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111)
Animal production (NAICS code 112)
Food manufacturing (NAICS code 311)
Pesticide manufacturing (NAICS 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-2005-0234. 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 https://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 https://www.epa.gov/edocket/ to submit or view public
comments, to 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
[[Page 48414]]
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.1. 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 on 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 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 https://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-2005-0234. 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-2005-0234. 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-2005-0234.
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-2005-0234. 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.
[[Page 48415]]
7. To ensure proper receipt by EPA, be sure to identify the docket
ID 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 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: August 11, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petitions
The petitioner's summary of the pesticide petitions is printed
below as required by FFDCA section 408(d)(3). The summary of the
petitions was prepared by Interregional Research Project Number 4 (IR-
4), and represents the view of the petitioner. The petion summary
announces the availabilty 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
PP 3E6582, PP 3E6596, PP 3E6750, PP 4E6865, PP 4E6866
EPA has received pesticide petitions (PP) 3E6582, 3E6596, 3E6750,
4E6865, and 4E6866 from the Interregional Research Project Number 4 IR-
4, Technology Center of New Jersey, Rutgers, the State University of
New Jersey, 681 U.S. Highway 1 S., North Brunswick, NJ 08902-
3390 proposing, pursuant to section 408(d) of the 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, in or on raw agricultural commodities as follows:
1. PP 3E6582 proposes a tolerance for white sapote and Ugli fruit
at 0.3 parts per million (ppm).
2. PP 3E6596 proposes a tolerance for legume vegetables, crop
subgroups 6a, 6b, and 6c at 0.2 ppm.
3. PP 3E6750 proposes a tolerance for onion, dry bulb at 0.05 ppm.
4. PP 4E6865 proposes a tolerance for strawberry at 0.3 ppm.
5. PP 4E6866 proposes a tolerance for grape at 2.5 ppm and raisin
at 4.0 ppm.
EPA has determined that the petitions contain 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
petitions. Additional data may be needed before EPA rules on the
petitions.
A. Residue Chemistry
1. Plant and animal metabolism. Metabolism of 14C-
pyriproxyfen labeled in the phenoxyphenyl ring and in the pyridyl ring
has been studied in cotton, apples, tomatoes, lactating goats, 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 commodities (RAC) samples remained as parent.
Comparing metabolites detected and quantified from cotton, apple,
tomato, goat, 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 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 or on all appropriate agricultural
commodities, respective processing fractions, milk, animal tissues, and
environmental samples. The extraction methodology has been validated
using aged radiochemical residue samples from metabolism studies. The
methods have been validated in cottonseed, apples, soil, and oranges at
independent laboratories. EPA has successfully validated the analytical
methods for analysis of cottonseed, 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. Residue data were generated with
pyriproxyfen for tolerance setting and dietary exposure estimates.
Adequate residue trials were performed with pyriproxyfen to support the
uses described in this notice of filing.
B. Toxicological Profile
An assessment of toxic effects caused by pyriproxyfen is discussed
in Unit III.A. and Unit III.B. of the Federal Register of April 4,
2001, (66 FR 17883) (FRL-6772-4).
1. 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 milligrams/
kilograms body weight (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 unlabeled material. For
all dose groups, most (-96%) of the administered radiolabel was
excreted in the urine and feces within 2 days after radiolabeled 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.
Radiocarbon concentrations in fat were 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.
2. 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
[[Page 48416]]
in the body, the potential 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 tolerated dose
(MTD) and consequent chronic exposure to the internally formed
metabolites.
Seven metabolites of pyriproxyfen, 4'-OH-pyriproxyfen, 5'-OH-
pyriproxyfen, desphenyl-pyriproxyfen, POPA, PYPAC, 2-OH-pyridine and
2,5-diOH-pyridine, have been tested for mutagenicity, via Ames Assay,
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 revertible colonies in any of the
test strains. Positive control chemicals showed marked increases in
reverting colonies. The acute toxicity to mice of 4'-OH-pyriproxyfen,
5'-OH-pyriproxyfen, desphenyl-pyriproxyfen, POPA, and PYPAC did not
appear to markedly differ from pyriproxyfen, with all metabolites
having acute oral lethal dose (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.
3. 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 some other 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
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, Valent Corporation concludes
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
assuming 100% of the crop will be treated with pyriproxyfen. The
analyses included residue data for all existing uses, pending uses, and
proposed new uses. The results from several representative subgroups
are listed below. Chronic dietary exposure to the overall U.S.
population is estimated to be 0.0238 mg/kg bwt/day, representing 6.8%
of the reference dose (RfD). For the most highly exposed sub-
population, infants, <1 years of age, dietary exposure is calculated to
be 0.0245 mg/kg bwt/day, or 7.0% of the RfD. 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.
ii. Drinking water. Since pyriproxyfen is applied outdoors to
growing agricultural crops, the potential exists for pyriproxyfen or
its metabolites to reach ground water 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
residue levels in drinking water are the peak chronic residue level as
estimated by GENEEC. Using standard assumptions about body weight and
water consumption, the chronic exposure to pyriproxyfen from this
drinking water would be 0.00009 mg/kg bwt/day for adults and ``0'' year
infants, and represent 0.025% of the RfD (0.35 mg/kg/day). 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 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-term 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 active ingredient (a.i.)/day, average body
weight for a 1-6 year old child of 10 kg, the a.i. dissipates uniformly
through 365 days (the label instructs to change the collar once a
year), 1% of the active ingredient 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 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 to pyriproxyfen and have similar effects on animals. In
consideration of potential
[[Page 48417]]
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.
E. Safety Determination
1. U.S. population--i. Chronic dietary exposure and risk to 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/day. The estimated chronic dietary
exposure from food for the overall U.S. population and many non-child/
infant subgroups is from 0.006 to 0.0245 mg/kg bwt/day, 1.7 to 7.0% 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 to 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 to 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 margin of exposure (MOE) for adults was 5,700.
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 10-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-natal and post-
natal 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 risk to 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 0.013 mg/kg bwt/
day children 6-12 years old, up to 0.0245 mg/kg bwt/day for infants (0
years of age), 3.8 and 7.0% of the RfD, respectively. Adding the worse
case potential incremental exposure to infants from pyriproxyfen in
drinking water (0.9 x 10-4 mg/kg bwt/day) does not
materially increase the aggregate, chronic dietary exposure and only
increases the occupancy of the RfD by 0.009%. 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. Valent
concludes 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 infants and children. No acute
dietary endpoint and dose were identified in the toxicology data base
for pyriproxyfen; therefore, Valent believes 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 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 1,425.
F. International Tolerances
There are presently no existing Codex maximum residue levels for
pyriproxyfen.
FR Doc. 05-16301 Filed 8-16-05; 8:45 a.m.]
BILLING CODE 6560-50-S