[Federal Register Volume 67, Number 103 (Wednesday, May 29, 2002)]
[Notices]
[Pages 37426-37432]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-13356]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2002-0074; FRL-7178-3]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket control number OPP-20020-0074, 
must be received on or before June 28, 2002.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket ID 
number OPP-2002-0074 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration

[[Page 37427]]

Support Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-6411; and e-mail 
address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

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

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

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

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register''--Environmental 
Documents. You can also go directly to the Federal Register listings at 
http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket ID number OPP-2002-0074. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as Confidential Business Information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall 2, 1921 Jefferson Davis Highway, Arlington, VA, 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket ID number OPP-2002-0074 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall 2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket ID number OPP-2002-0074. Electronic comments may 
also be filed online at many Federal Depository Libraries.

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

     Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

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

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
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 section 408(d)(2); however, EPA

[[Page 37428]]

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: May 16, 2002.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

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

Valent U.S.A. Corporation

PP 2F6385

     EPA has received a pesticide petition (2F6385) from Valent U.S.A. 
Corporation, 1333 North California Boulevard, Suite 600, Walnut Creek, 
CA 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 a tolerance for residues of pyriproxyfen, 
2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine, in or on the raw 
agricultural commodity vegetable, brassica, leafy, group (crop group 5) 
at 2.5 parts per million (ppm); vegetable, cucurbit, group (crop group 
9) at 0.1 ppm; and olive at 1.0 ppm; and in the processed commodity 
olive, oil at 3.0 ppm. EPA has determined that the petition contains 
data or information regarding the elements set forth in section 
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
support granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. Metabolism of 14C-pyriproxyfen 
labelled in the phenoxyphenyl ring and in the pyridyl ring has been 
studied in cotton, apples, tomatoes, lactating goats, and laying hens 
(and rats). The major metabolic pathways in plants is aryl 
hydroxylation and cleavage of the ether linkage, followed by further 
metabolism into more polar products by further oxidation and/or 
conjugation reactions. However, the bulk of the radiochemical residue 
on raw agricultural commodity samples remained as parent. Comparing 
metabolites detected and quantified from cotton, apple, tomato, goat, 
and hen (and rat) shows that there are no significant aglycones in 
plants which are not also present in the excreta or tissues of animals. 
The residue of concern is best defined as the parent, pyriproxyfen.
     Ruminant and poultry metabolism studies demonstrated that transfer 
of administered 14C-residues to tissues was low. Total 
14C-residues in goat milk, muscle and tissues accounted for 
less than 2% of the administered dose, and were less than 1 ppm in all 
cases. In poultry, total 14C-residues in eggs, muscle and 
tissues accounted for about 2.7% of the administered dose, and were 
less than 1 ppm in all cases except for gizzard.
    2. Analytical method. 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 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--i. Vegetable, brassica, leafy, group. 
Seven field trials in cabbage were conducted in 1999 and 2000. 
Similarly, seven field trials were conducted for cauliflower and six 
field trials were conducted for mustard greens. The proposed use 
pattern for the three vegetable, brassica, leafy, crops is identical. 
The analytical data show that the average measured residue in/on 
cabbage samples was 0.14 ppm (n = 14, [sigma]n-1 = 0.12 ppm) 
pyriproxyfen. Similarly, the analytical data show that the average 
measured residue in/on cauliflower samples was 0.03 ppm (n = 14, 
[sigma]n-1 = 0.05 ppm), and in/on mustard green samples was 
0.70 ppm (n = 12, [sigma]n-1 = 0.53 ppm), of pyriproxyfen. 
The highest average residue (HAR) from field trials was 1.6 ppm. These 
data support a proposed tolerance for pyriproxyfen in/on the vegetable, 
brassica, leafy, group at 2.5 ppm.
    ii. Vegetable, cucurbit, group. Seven field trials in cantaloupe 
were conducted in 1999 and 2000. Similarly, six field trials were 
conducted for cucumber and six field trials were conducted for summer 
squash. The proposed use pattern for the three vegetable, cucurbit, 
crops is identical. The analytical data show that the average measured 
residue in/on cantaloupe samples was 0.02 ppm (n = 14, 
[sigma]n-1 = 0.01 ppm) pyriproxyfen. Similarly, the 
analytical data show that the average measured residue of pyriproxyfen 
in/on cucumber and summer squash samples was below the residue method 
``Limit of Detection'' of 0.01 ppm. The HAR from field trials was 0.04 
ppm. These data support a proposed tolerance for pyriproxyfen in/on the 
vegetable, cucurbit, group at 0.1 ppm.
    iii. Olive. Four field trials in olive were conducted in 2000. The 
analytical data show that the average measured residue in/on olive 
samples was 0.37 ppm (n = 8, [sigma]n-1 = 0.24 ppm) 
pyriproxyfen. A processing study in olive demonstrated that 
pyriproxyfen concentrated in olive oil (3-fold). The HAR from field 
trials was 0.73 ppm. These data support proposed tolerances for 
pyriproxyfen in/on olive at 1.0 ppm and olive oil at 3.0 ppm.
    iv. Secondary residues. No additional feed commodities are 
associated with the new proposed use on vegetable, brassica, leafy, 
group; vegetable, cucurbit, group; and olive. Using established 
tolerances to calculate the maximum feed exposure to fed 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.
    v. 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

[[Page 37429]]

acute oral toxicity, and skin/eye irritation. Pyriproxyfen is not a 
skin sensitizing agent.
    2. Genotoxicty. 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 body weight/day (mg/kg bw/day) during 
gestation days 7-17. Maternal toxicity (mortality, decreased body 
weight gain and food consumption, and clinical signs of toxicity) was 
observed at doses of 300 mg/kg bw/day and greater. The maternal no 
observed adverse effect level (NOAEL) was 100 mg/kg bw/day. A transient 
increase in skeletal variations was observed in rat fetuses from 
females exposed to 300 mg/kg bw/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 
bw/day. An increased incidence of visceral and skeletal variations was 
observed postnatally at 1,000 mg/kg bw/day. The NOAEL for postnatal 
developmental toxicity was 300 mg/kg bw/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 bw/day during gestation days 6-18. Maternal 
toxicity (clinical signs of toxicity including one death, decreased 
body weight gain and food consumption, and abortions or premature 
deliveries) was observed at oral doses of 300 mg/kg bw/day or higher. 
The maternal NOAEL was 100 mg/kg bw/day. No developmental effects were 
observed in the rabbit fetuses. The NOAEL for developmental toxicity in 
rabbits was 1,000 mg/kg bw/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 body weights, 
liver and kidney histopathology, and increased liver weight) was 
produced at the 5,000 ppm dose (453 mg/kg bw/day in males, 498 mg/kg 
bw/day in females) during the pre-mating period. The systemic NOAEL was 
1,000 ppm (87 mg/kg bw/day in males, 96 mg/kg bw/day in females). No 
effects on reproduction were produced at 5,000 ppm, the highest 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 body weight gain; increased liver weights; 
histopathological changes in the liver and kidney; decreased red blood 
cell counts, hemoglobin and hematocrit; altered blood chemistry 
parameters; and, at 5,000 and 10,000 ppm in mice, a decrease in 
survival rates. The NOAELs from these studies were 400 ppm (23.5 mg/kg 
bw/day for males, 27.7 mg/kg bw/day for females) in rats, 1,000 ppm 
(149.4 mg/kg bw/day for males, 196.5 mg/kg bw/day for females) in mice, 
and 100 mg/kg bw/day in dogs.
     In a 4-week inhalation study of pyriproxyfen technical in rats, 
decreased body weight 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 
bw/day, the highest dose tested. In a 21-day dermal study conducted 
with KNACK[reg] Insect Growth Regulator, the test material 
produced a NOAEL of 1,000 mg/kg bw/day HDT for systemic effects, and a 
NOAEL for skin irritation of 100 mg/kg bw/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 bw/day, based on 
the NOAEL in female rats from the 2-year chronic/oncogenicity study. 
Effects cited by EPA in the Reference Dose 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 cancer in test animals. 
No oncogenic response was observed in a rat 2-year chronic feeding/
oncogenicity study or in a 78-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 bw/day for 1 year. Dogs 
exposed to dose levels of 300 mg/kg bw/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 bw/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 bw/day in males, 109.5 mg/
kg bw/day in females), and a LOAEL of 3,000 ppm (420 mg/kg bw/day in 
males, 547 mg/kg bw/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 bw/day in 
males, 35.1 mg/kg bw/day in females). A LOAEL of 3,000 ppm (138 mg/kg 
bw/day in males, 182.7 mg/kg bw/day in females) was established based 
on a depression in body weight gain in females.
    6. Animal metabolism. The absorption, tissue distribution, 
metabolism and excretion of 14C-labeled pyriproxyfen were 
studied in rats after single oral doses of 2 or 1,000 mg/kg bw 
(phenoxyphenyl and pyridyl label), and after a single oral dose of 2 
mg/kg bw (phenoxyphenyl label only) following 14 daily oral doses at 2 
mg/kg bw of unlabelled material. For all dose groups, most (88-96%) of 
the administered radiolabel was excreted in the urine and feces within 
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 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

[[Page 37430]]

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 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 tolerance 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 (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' '-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 bw. The two 
pyridines, 2-OH-pyridine and 2,5-diOH-pyridine, gave acute oral 
LD50 values of 124 (male) and 166 (female) mg/kg bw, and 
1,105 (male) and 1,000 (female) mg/kg bw, 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 
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 25 population subgroups assuming 
tolerance level residues, processing factors from residue studies, and 
100% of the crop treated. 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 exposure to 
the overall U.S. population is estimated to be 0.002984 mg/kg bw/day, 
representing 0.9% of the RfD. For the most highly exposed sub-
population, children 1 to 6 years of age, exposure is calculated to be 
0.007438 mg/kg bw/day, or 2.1% 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 percent of the 
RfD.

  Calculated Chronic Dietary Exposures to the Total U.S. Population and
        Selected Sub-Populations to Pyriproxyfen Residues in Food
------------------------------------------------------------------------
                                  Exposure (mg/kg bw/
       Population subgroup               day)           Percent of RfD
------------------------------------------------------------------------
Total U.S. population (all        0.002984..........  0.853
 seasons)
------------------------------------------------------------------------
Children (1-6 Years)              0.007438..........  2.125
------------------------------------------------------------------------
Non-Nursing Infants (<1 Year      0.006483..........  1.852
 Old)
------------------------------------------------------------------------
All Infants (<1 Year Old)         0.005604..........  1.601
------------------------------------------------------------------------
Children (7-12 Years)             0.004159..........  1.188
------------------------------------------------------------------------
Children (1-6 Years)              0.007438..........  2.125
------------------------------------------------------------------------
Females (13+/Nursing)             0.002964..........  0.847
------------------------------------------------------------------------
Nursing Infants (<1 Year Old)     0.002601..........  0.743
------------------------------------------------------------------------

    ii. Drinking water. Since pyriproxyfen is applied outdoors to 
growing agricultural crops, the potential exists for pyriproxyfen or 
its metabolites to reach ground or surface water that may be used for 
drinking water. Because of the physical properties of pyriproxyfen, it 
is unlikely that pyriproxyfen or its metabolites can leach to potable 
ground water. To quantify potential exposure from drinking water, 
surface water concentrations for pyriproxyfen were estimated using 
GENEEC 1.3. The average 56-day concentration predicted in the simulated 
pond water was 0.16 ppb. Using standard assumptions about body weight 
and water consumption, the chronic exposure to pyriproxyfen from this 
drinking water would be 4.57 x 10-6 and 1.6 x 
10-5 mg/kg bw/day for adults and children, respectively; 
0.0046% of the RfD (0.35 mg/kg/day) for children. 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

[[Page 37431]]

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 body 
weight for a 1-6 year old child of 10 kg, the active ingredient 
dissipates uniformly through 365 days (the label instruct to change 
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 cumulative effects of pyriproxyfen and other 
substances that may have a common mechanism of toxicity, there are 
currently no available data or other reliable information indicating 
that any toxic effects produced by pyriproxyfen would be cumulative 
with those of other chemical compounds. Thus, only the potential risks 
of pyriproxyfen have been considered in this assessment of aggregate 
exposure and effects.
     Valent will submit information for EPA to consider concerning 
potential cumulative effects of pyriproxyfen consistent with the 
schedule established by EPA at (62 FR 42019) (FRL-5734-6) August 4, 
1997 and other subsequent EPA publications pursuant to the Food Quality 
Protection Act.

E. Safety Determination

    1. U.S. population--i. Chronic dietary exposure and risk.--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 bw/day. The estimated chronic 
dietary exposure from food for the overall U.S. population and many 
non-child/infant subgroups is from 0.002123 to 0.003884 mg/kg bw/day, 
0.607 to 1.100% of the RfD. Addition of the small but worse case 
potential chronic exposure from drinking water (calculated above) 
increases exposure by only 4.57 x 10-6 mg/kg bw/day and does 
not change the maximum occupancy of the RfD significantly. Generally, 
the Agency has no cause for concern if total residue contribution is 
less than 100% 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. --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. --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. 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 risk. 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 0.002601 mg/kg bw/day for nursing infants, up 
to 0.007438 mg/kg bw/day for children (1-6 years of age), 0.743 to 
2.125% of the RfD, respectively. Adding the worse case potential 
incremental exposure to infants and children from pyriproxyfen in 
drinking water (1.6 x 10-5 mg/kg bw/day) does not materially 
increase the aggregate, chronic dietary exposure and only increases the 
occupancy of the RfD by 0.0046% to 2.130% for children (1-6 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. No acute dietary endpoint and 
dose were identified in the toxicology data

[[Page 37432]]

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. 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 maximum residue levels 
maximum residue levels for pyriproxyfen.
[FR Doc. 02-13356 Filed 5-28-02; 8:45 am]
BILLING CODE 6560-50-S