76724 Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 

certainty that no harm will occur to 

infants and children from aggregate 

exposure to residues of buprofezin.

F. International Tolerances

Canada, Codex, and Mexico do not 

have maximum residue limits for 

residues of buprofezin in/on the 

proposed crops. Therefore, 

harmonization is not an issue.

[FR Doc. 04–27772 Filed 12–21–04; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION 

AGENCY

[OPP–2004–0403; FRL–7689–6]

Pyriproxyfen: Notice of Filing a 

Pesticide Petition to Establish a 

Tolerance for a Certain Pesticide 

Chemical in or on Food

AGENCY: Environmental Protection 

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the 

initial filing of a pesticide petition 

proposing the establishment of 

regulations for residues of a certain 

pesticide chemical in or on various food 

commodities.

DATES: Comments, identified by docket 

identification (ID) number OPP–2004–

0403, must be received on or before 

January 21, 2005.

ADDRESSES: Comments may be 

submitted electronically, by mail, or 

through hand delivery/courier. Follow 

the detailed instructions as provided in 

Unit I. of the SUPPLEMENTARY

INFORMATION.

FOR FURTHER INFORMATION CONTACT:

Joseph Tavano, Registration Division 

(7505C), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 

(703) 305–6411; e-mail address: 

tavano.joseph@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be potentially affected by 

this action if you an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. Potentially 

affected entities may include, but are 

not limited to:

• Crop production (NAICS 111)

• Animal production (NAICS 112)

• Food manufacturing (NAICS 311)

• Pesticide manufacturing (NAICS 

32532)

This listing is not intended to be 

exhaustive, but rather provides a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT.

B. How Can I Get Copies of this 

Document and Other Related 

Information?

1. Docket. EPA has established an 

official public docket for this action 

under docket ID number OPP–2004–

0403. The official public docket consists 

of the documents specifically referenced 

in this action, any public comments 

received, and other information related 

to this action. Although a part of the 

official docket, the public docket does 

not include Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

The official public docket is the 

collection of materials that is available 

for public viewing at the Public 

Information and Records Integrity 

Branch (PIRIB), Rm. 119, Crystal Mall 

#2, 1801 S. Bell St., Arlington, VA. This 

docket facility is open from 8:30 a.m. to 

4 p.m., Monday through Friday, 

excluding legal holidays. The docket 

telephone number is (703) 305–5805.

2. Electronic access. You may access 

this Federal Register document 

electronically through the EPA Internet 

under the ‘‘Federal Register’’ listings at 

http://www.epa.gov/fedrgstr/.

An electronic version of the public 

docket is available through EPA’s 

electronic public docket and comment 

system, EPA Dockets. You may use EPA 

Dockets at http://www.epa.gov/edocket/

to submit or view public comments, 

access the index listing of the contents 

of the official public docket, and to 

access those documents in the public 

docket that are available electronically. 

Although not all docket materials may 

be available electronically, you may still 

access any of the publicly available 

docket materials through the docket 

facility identified in Unit I.B.1. Once in 

the system, select ‘‘search,’’ then key in 

the appropriate docket ID number.

Certain types of information will not 

be placed in the EPA Dockets. 

Information claimed as CBI and other 

information whose disclosure is 

restricted by statute, which is not 

included in the official public docket, 

will not be available for public viewing 

in EPA’s electronic public docket. EPA’s 

policy is that copyrighted material will 

not be placed in EPA’s electronic public 

docket but will be available only in 

printed, paper form in the official public 

docket. To the extent feasible, publicly 

available docket materials will be made 

available in EPA’s electronic public 

docket. When a document is selected 

from the index list in EPA Dockets, the 

system will identify whether the 

document is available for viewing in 

EPA’s electronic public docket. 

Although not all docket materials may 

be available electronically, you may still 

access any of the publicly available 

docket materials through the docket 

facility identified in Unit I.B. EPA 

intends to work towards providing 

electronic access to all of the publicly 

available docket materials through 

EPA’s electronic public docket.

For public commenters, it is 

important to note that EPA’s policy is 

that public comments, whether 

submitted electronically or in paper, 

will be made available for public 

viewing in EPA’s electronic public 

docket as EPA receives them and 

without change, unless the comment 

contains copyrighted material, CBI, or 

other information whose disclosure is 

restricted by statute. When EPA 

identifies a comment containing 

copyrighted material, EPA will provide 

a reference to that material in the 

version of the comment that is placed in 

EPA’s electronic public docket. The 

entire printed comment, including the 

copyrighted material, will be available 

in the public docket.

Public comments submitted on 

computer disks that are mailed or 

delivered to the docket will be 

transferred to EPA’s electronic public 

docket. Public comments that are 

mailed or delivered to the docket will be 

scanned and placed in EPA’s electronic 

public docket. Where practical, physical 

objects will be photographed, and the 

photograph will be placed in EPA’s 

electronic public docket along with a 

brief description written by the docket 

staff.

C. How and to Whom Do I Submit 

Comments?

You may submit comments 

electronically, by mail, or through hand 

delivery/courier. To ensure proper 

receipt by EPA, identify the appropriate 

docket ID number in the subject line on 

the first page of your comment. Please 

ensure that your comments are 

submitted within the specified comment 

period. Comments received after the 

close of the comment period will be 

marked ‘‘late.’’ EPA is not required to 

consider these late comments. If you 

wish to submit CBI or information that 

Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 76725

is otherwise protected by statute, please 

follow the instructions in Unit I.D. Do 

not use EPA Dockets or e-mail to submit 

CBI or information protected by statute.

1. Electronically. If you submit an 

electronic comment as prescribed in this 

unit, EPA recommends that you include 

your name, mailing address, and an email address or other contact 

information in the body of your 

comment. Also include this contact 

information on the outside of any disk 

or CD ROM you submit, and in any 

cover letter accompanying the disk or 

CD ROM. This ensures that you can be 

identified as the submitter of the 

comment and allows EPA to contact you 

in case EPA cannot read your comment 

due to technical difficulties or needs 

further information on the substance of 

your comment. EPA’s policy is that EPA 

will not edit your comment, and any 

identifying or contact information 

provided in the body of a comment will 

be included as part of the comment that 

is placed in the official public docket, 

and made available in EPA’s electronic 

public docket. If EPA cannot read your 

comment due to technical difficulties 

and cannot contact you for clarification, 

EPA may not be able to consider your 

comment.

i. EPA Dockets. Your use of EPA’s 

electronic public docket to submit 

comments to EPA electronically is 

EPA’s preferred method for receiving 

comments. Go directly to EPA Dockets 

at http://www.epa.gov/edocket/, and 

follow the online instructions for 

submitting comments. Once in the 

system, select ‘‘search,’’ and then key in 

docket ID number OPP–2004–0403. The 

system is an ‘‘anonymous access’’

system, which means EPA will not 

know your identity, e-mail address, or 

other contact information unless you 

provide it in the body of your comment.

ii. E-mail. Comments may be sent by 

e-mail to opp-docket@epa.gov, 

Attention: Docket ID number OPP–

2004–0403. In contrast to EPA’s 

electronic public docket, EPA’s e-mail 

system is not an ‘‘anonymous access’’

system. If you send an e-mail comment 

directly to the docket without going 

through EPA’s electronic public docket, 

EPA’s e-mail system automatically 

captures your e-mail address. E-mail 

addresses that are automatically 

captured by EPA’s e-mail system are 

included as part of the comment that is 

placed in the official public docket, and 

made available in EPA’s electronic 

public docket.

iii. Disk or CD ROM. You may submit 

comments on a disk or CD ROM that 

you mail to the mailing address 

identified in Unit I.C.2. These electronic 

submissions will be accepted in 

WordPerfect or ASCII file format. Avoid 

the use of special characters and any 

form of encryption.

2. By mail. Send your comments to: 

Public Information and Records 

Integrity Branch (PIRIB) (7502C), Office 

of Pesticide Programs (OPP), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001, Attention: Docket ID 

number OPP–2004–0403.

3. By hand delivery or courier. Deliver 

your comments to: Public Information 

and Records Integrity Branch (PIRIB), 

Office of Pesticide Programs (OPP), 

Environmental Protection Agency, Rm. 

119, Crystal Mall #2, 1801 S. Bell St., 

Arlington, VA, Attention: Docket ID 

number OPP–2004–0403. Such 

deliveries are only accepted during the 

docket’s normal hours of operation as 

identified in Unit I.B.1.

D. How Should I Submit CBI to the 

Agency?

Do not submit information that you 

consider to be CBI electronically 

through EPA’s electronic public docket 

or by e-mail. You may claim 

information that you submit to EPA as 

CBI by marking any part or all of that 

information as CBI (if you submit CBI 

on disk or CD ROM, mark the outside 

of the disk or CD ROM as CBI and then 

identify electronically within the disk or 

CD ROM the specific information that is 

CBI). Information so marked will not be 

disclosed except in accordance with 

procedures set forth in 40 CFR part 2.

In addition to one complete version of 

the comment that includes any 

information claimed as CBI, a copy of 

the comment that does not contain the 

information claimed as CBI must be 

submitted for inclusion in the public 

docket and EPA’s electronic public 

docket. If you submit the copy that does 

not contain CBI on disk or CD ROM, 

mark the outside of the disk or CD ROM 

clearly that it does not contain CBI. 

Information not marked as CBI will be 

included in the public docket and EPA’s 

electronic public docket without prior 

notice. If you have any questions about 

CBI or the procedures for claiming CBI, 

please consult the person listed under 

FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare 

My Comments for EPA?

You may find the following 

suggestions helpful for preparing your 

comments:

1. Explain your views as clearly as 

possible.

2. Describe any assumptions that you 

used.

3. Provide copies of any technical 

information and/or data you used that 

support your views.

4. If you estimate potential burden or 

costs, explain how you arrived at the 

estimate that you provide.

5. Provide specific examples to 

illustrate your concerns.

6. Make sure to submit your 

comments by the deadline in this 

notice.

7. To ensure proper receipt by EPA, 

be sure to identify the docket ID number 

as signed to this action in the subject 

line on the first page of your response. 

You may also provide the name, date, 

and Federal Register citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition 

as follows proposing the establishment 

and/or amendment of regulations for 

residues of a certain pesticide chemical 

in or on various food commodities 

under section 408 of the Federal Food, 

Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a. EPA has determined that 

this petition contains data or 

information regarding the elements set 

forth in FFDCA section 408(d)(2); 

however, EPA has not fully evaluated 

the sufficiency of the submitted data at 

this time or whether the data support 

granting of the petition. Additional data 

may be needed before EPA rules on the 

petition.

List of Subjects

Environmental protection, 

Agricultural commodities, Feed 

additives, Food additives, Pesticides 

and pests, Reporting and recordkeeping 

requirements.

Dated: December 9, 2004.

Lois Rossi,

Director, Registration Division, Office of 

Pesticide Programs.

Summary of Petition

The petitioner summary of the 

pesticide petition is printed below as 

required by FFDCA section 408(d)(3). 

The summary of the petition was 

prepared by the petitioner and 

represents the view of the petitioner. 

The petition summary announces the 

availability of a description of the 

analytical methods available to EPA for 

the detection and measurement of the 

pesticide chemical residues or an 

explanation of why no such method is 

needed.

Valent U.S.A. Corporation

PP 4F6847

EPA has received a pesticide petition 

4F6847 from Valent U.S.A. Corporation, 

1600 Riviera Ave., Suite 200, Walnut 

76726 Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 

Creek, California 94596–8025 

proposing, pursuant to section 408(d) of 

the Federal Food, Drug, and Cosmetic 

Act (FFDCA), 21 U.S.C. 346a(d), to 

amend 40 CFR part 180 by establishing 

tolerances for residues of pyriproxyfen, 

2-[1-methyl-2-(4-

phenoxyphenoxy)ethoxy]pyridine (CA), 

in or on the raw agricultural 

commodities (RAC) grass forage and hay 

(crop group 17). EPA has determined 

that the petition contains data or 

information regarding the elements set 

forth in section 408(d)(2) of the FFDCA; 

however, EPA has not fully evaluated 

the sufficiency of the submitted data at 

this time or whether the data supports 

granting of the petition. Additional data 

may be needed before EPA rules on the 

petition.

A. Residue Chemistry

1. Plant metabolism. Metabolism of 14C-pyriproxyfen labeled in the 

phenoxyphenyl ring and in the pyridyl 

ring has been studied in cotton, apples, 

tomatoes, lactating goats, and laying 

hens (and rats). The major metabolic 

pathways in plants is aryl hydroxylation 

and cleavage of the ether linkage, 

followed by further metabolism into 

more polar products by further 

oxidation and/or conjugation reactions. 

However, the bulk of the radio-chemical 

residue on RAC samples remained as 

parent. Comparing metabolites detected 

and quantified from cotton, apple, 

tomato, goat and hen (and rat) shows 

that there are no significant metabolites 

in plants which are not also present in 

the excreta or tissues of animals. 

Therefore, the residue of concern is best 

defined as the parent, pyriproxyfen.

Ruminant and poultry metabolism 

studies demonstrated that transfer of 

administered 14C-residues to tissues was 

low. Total 14C-residues in goat milk, 

muscle and tissues accounted for less 

than 2% of the administered dose, and 

were less than 1 part per million (ppm) 

in all cases. In poultry, total 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/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 cotton seed, apples, 

soil, and oranges at independent 

laboratories. EPA has successfully 

validated the analytical methods for 

analysis of cotton seed, pome fruit, 

nutmeats, almond hulls, and fruiting 

vegetables. The limit of detection of 

pyriproxyfen in the methods is 0.01 

ppm which will allow monitoring of 

food with residues at the levels 

proposed for the tolerances.

3. Magnitude of residues—i. Grass, 

forage, fodder, and hay. Twelve field 

trials in grass were conducted in 2002 

and 2003. The analytical data show that 

the average measured residue in/on 

grass forage samples was 0.05 ppm (n = 

24, sn-1 = 0.10 ppm) pyriproxyfen. 

Similarly, the analytical data show that 

the average measured residue in/on 

grass hay samples was 0.10 ppm (n = 24, 

sn-1 = 0.19 ppm). These data support a 

proposed tolerance for pyriproxyfen in/

on grass forage of 0.5 ppm and grass hay 

of 1.0 ppm.

ii. Secondary residues. The proposed 

new use on grass represents an 

additional feed commodity. Using 

established and proposed tolerances to 

calculate the maximum feed exposure to 

feed animals, and using the very low 

potential for residue transfer 

demonstrated in the milk cow feeding 

residue study, detectable secondary 

residues in animal tissues, milk, and 

eggs are not expected. Therefore, no 

tolerances are required for these 

commodities.

iii. Rotational crops. The results of a 

confined rotational crops accumulation 

study indicate that no rotational crop 

planting restrictions or rotational crop 

tolerances are required.

B. Toxicological Profile

1. Acute toxicity. The acute toxicity of 

technical grade pyriproxyfen is low by 

all routes. The compound is classified 

as Category III for acute dermal and 

inhalation toxicity, and Category IV for 

acute oral toxicity, and skin/eye 

irritation. Pyriproxyfen is not a skin 

sensitizing agent.

2. Genotoxicity. Pyriproxyfen does not 

present a genetic hazard. Pyriproxyfen 

was negative in the following tests for 

mutagenicity: Ames assay with and 

without S9, in vitro unscheduled DNA 

synthesis in HeLa S3 cells, in vitro gene 

mutation in V79 Chinese hamster cells, 

and in vitro chromosomal aberration 

with and without S9 in Chinese hamster 

ovary cells.

3. Reproductive and developmental 

toxicity. Pyriproxyfen is not a 

developmental or reproductive toxicant. 

Developmental toxicity studies have 

been performed in rats and rabbits, and 

multigenerational effects on 

reproduction were tested in rats. These 

studies have been reviewed and found 

to be acceptable to the Agency.

In the developmental toxicity study 

conducted with rats, technical 

pyriproxyfen was administered by 

gavage at levels of 0, 100, 300, and 1,000 

milligrams/kilogram/bodyweight day 

(mg/kg/bwt day) during gestation days 

7–17. Maternal toxicity (mortality, 

decreased bwt gain and food 

consumption, and clinical signs of 

toxicity) was observed at doses of 300 

mg/kg/bwt day and greater. The 

maternal no observed adverse effect 

level (NOAEL) was 100 mg/kg/bwt day. 

A transient increase in skeletal 

variations was observed in rat fetuses 

from females exposed to 300 mg/kg/bwt 

day and greater. These effects were not 

present in animals examined at the end 

of the postnatal period, therefore, the 

NOAEL for prenatal developmental 

toxicity was 100 mg/kg/bwt day. An 

increased incidence of visceral and 

skeletal variations was observed 

postnatally at 1,000 mg/kg/bwt day. The 

NOAEL for postnatal developmental 

toxicity was 300 mg/kg/bwt day.

In the developmental toxicity study 

conducted with rabbits, technical 

pyriproxyfen was administered by 

gavage at levels of 0, 100, 300, and 1,000 

mg/kg/bwt day during gestation days 6–

18. Maternal toxicity (clinical signs of 

toxicity including one death, decreased 

bwt gain and food consumption, and 

abortions or premature deliveries) was 

observed at oral doses of 300 mg/kg/bwt 

day or higher. The maternal NOAEL was 

100 mg/kg/bwt day. No developmental 

effects were observed in the rabbit 

fetuses. The NOAEL for developmental 

toxicity in rabbits was 1,000 mg/kg/bwt 

day.

In the rat reproduction study, 

pyriproxyfen was administered in the 

diet at levels of 0, 200, 1,000, and 5,000 

ppm through two generations of rats. 

Adult systemic toxicity (reduced bwts, 

liver and kidney histopathology, and 

increased liver weight) was produced at 

the 5,000 ppm dose (453 mg/kg/bwt day 

in males, 498 mg/kg/bwt day in females) 

during the pre-mating period. The 

systemic NOAEL was 1,000 ppm (87 

mg/kg/bwt day in males, 96 mg/kg/bwt 

day in females). No effects on 

reproduction were produced at 5,000 

ppm, the higest dose tested (HDT).

4. Subchronic toxicity. Subchronic 

oral toxicity studies conducted with 

pyriproxyfen technical in the rat, 

mouse, and dog indicate a low level of 

toxicity. Effects observed at high dose 

levels consisted primarily of decreased 

bwt gain; increased liver weights; 

histopathological changes in the liver 

and kidney; decreased red blood cell 

counts, hemoglobin and hematocrit; 

Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 76727

altered blood chemistry parameters; 

and, at 5,000 and 10,000 ppm in mice, 

adecrease in survival rates. The 

NOAELs from these studies were 400 

ppm (23.5 mg/kg/bwt day for males, 

27.7 mg/kg/bwt day for females) in rats, 

1,000 ppm (149.4 mg/kg/bwt day for 

males, 196.5 mg/kg/bwt day for females) 

in mice, and 100 mg/kg/bwt day in 

dogs. In a four week inhalation study of 

pyriproxyfen technical in rats, 

decreased bwt and increased water 

consumption were observed at 1,000 

mg/m3. The NOAEL in this study was 

482 mg/m3.

A 21-day dermal toxicity study in rats 

with pyriproxyfen technical did not 

produce any signs of dermal or systemic 

toxicity at 1,000 mg/kg/bwt day, the 

HDT. In a 21-day dermal study 

conducted with KNACK. Insect 

Growth Regulator, the test material 

produced a NOAEL of 1,000 mg/kg/bwt 

day HDT for systemic effects, and a 

NOAEL for skin irritation of 100 mg/kg/

bwt day.

5. Chronic toxicity. Pyriproxyfen 

technical has been tested in chronic 

studies with dogs, rats, and mice. EPA 

has established a reference dose (RfD) 

for pyriproxyfen of 0.35 mg/kg/bwt day, 

based on the NOAEL in female rats from 

the 2-year chronic/oncogenicity study. 

Effects cited by EPA in the RfD Tracking 

Report include negative trend in mean 

red blood cell volume, increased 

hepatocyte cytoplasm and cytoplasm: 

Nucleus ratios, and decreased 

sinusoidal spaces.

Pyriproxyfen is not a carcinogen. 

Studies with pyriproxyfen have shown 

that repeated high dose exposures 

produced changes in the liver, kidney, 

and red blood cells, but did not produce 

cancerin test animals. No oncogenic 

response was observed in a rat 2-year 

chronic feeding/oncogenicity study or 

in a seventy-eight week study on mice. 

The oncogenicity classification of 

pyriproxyfen is ‘‘E’’ (no evidence of 

carcinogenicity for humans).

Pyriproxyfen technical was 

administered to dogs in capsules at 

doses of 0, 30, 100, 300, and 1,000 mg/

kg/bwt day for 1-year. Dogs exposed to 

dose levels of 300 mg/kg/bwt day or 

higher showed overt clinical signs of 

toxicity, elevated levels of blood 

enzymes and liver damage. The NOAEL 

in this study was 100 mg/kg/bwt day.

Pyriproxyfen technical was 

administered to mice at doses of 0, 120, 

600, and 3,000 ppm in diet for 78–

weeks. The NOAEL for systemic effects 

in this study was 600 ppm (84 mg/kg/

bwt day in males, 109.5 mg/kg/bwt day 

in females), and a LOAEL of 3,000 ppm 

(420 mg/kg/bwt day in males, 547 mg/

kg/bwt day in females) was established 

based on an increase in kidney lesions.

In a 2-year study in rats, pyriproxyfen 

technical was administered in the diet 

at levels of 0, 120, 600, and 3,000 ppm. 

The NOAEL for systemic effects in this 

study was 600 ppm (27.31 mg/kg/bwt 

day in males, 35.1 mg/kg/bwt day in 

females). A lowest observed adverse 

effect level (LOAEL) of 3,000 ppm (138 

mg/kg/bwt day inmales, 182.7 mg/kg/

bwt day in females) was established 

based on a depression in bwt gain in 

females.

6. Animal metabolism. The 

absorption, tissue distribution, 

metabolism and excretion of 14C-labeled 

pyriproxyfen were studied in rats after 

single oral doses of 2 or 1,000 mg/kg/

bwt (phenoxyphenyl and pyridyl label), 

and after a single oral dose of 2 mg/kg/

bwt (phenoxyphenyl label only) 

following 14 daily oral doses at 2 mg/

kg/bwt of unlabelled material. For all 

dose groups, most (88–96%) of the 

administered radio-label was excreted 

in the urine and feces within 2–days 

after radio- labeled test material dosing, 

and 92–98% of the administered dose 

was excreted within 7–days. Seven–

days after dosing, tissue residues were 

generally low, accounting for no more 

than 0.3% of the dosed 14C. 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 

7–days. Tissue residues were low 7–

days after dosing, accounting for no 

more than 0.3% of the dosed 14C. 

Because parent and metabolites are not 

retained in the body, the potentil for 

acute toxicity from in situ formed 

metabolites is low. The potential for 

chronic toxicity is adequately tested by 

chronic exposure to the parent at the 

maximum tolerance dose and 

consequent chronic exposure to the 

internally formed metabolites.

Seven metabolites of pyriproxyfen, 4’-

OH-pyriproxyfen, 5’3’-OH-pyriproxyfen, 

desphenyl-pyriproxyfen, POPA, PYPAC, 

2-OH-pyridine and 2,5-diOH-pyridine, 

have been tested for mutagenicity 

(Ames) and acute oral toxicity to mice. 

All seven metabolites were tested in the 

Ames assay with and without S9 at 

doses up to 5,000 micro-grams per plate 

or up to the growth inhibitory dose. The 

metabolites did not induce any 

significant increases in revertant 

colonies in any of the test strains. 

Positive control chemicals showed 

marked increases in revertant colonies. 

The acute toxicity to mice of 4’-OHpyriproxyfen, 5’3’-OH-pyriproxyfen, 

desphenyl-pyriproxyfen, POPA, and 

PYPAC did not appear to markedly 

differ from pyriproxyfen, with all 

metabolites having acute oral LD50

values greater than 2,000 mg/kg/bwt. 

The two pyridines, 2-OH-pyridine and 

2,5-diOH-pyridine, gave acute oral LD50

values of 124 (male), and 166 (female) 

mg/kg/bwt, and 1,105 (male) and 1,000 

(female) mg/kg/bwt, respectively.

8. Endocrine disruption. Pyriproxyfen 

is specifically designed to be an insect 

growth regulator and is known to 

produce juvenoid effects on arthropod 

development. However, this 

mechanism-of-action in target insects 

and other some arthropods has no 

relevance to any mammalian endocrine 

system. While specific tests, uniquely 

designed to evaluate the potential 

effects of pyriproxyfen on mammalian 

endocrine systems have not been 

conducted, the toxicology of 

pyriproxyfen has been extensively 

evaluated in acute, sub-chronic, 

chronic, developmental, and 

reproductive toxicology studies 

including detailed histopathology of 

numerous tissues. The results of these 

studies show no evidence of any 

endocrine-mediated effects and no 

pathology of the endocrine organs. 

Consequently, it is concluded that 

pyriproxyfen does not possess 

estrogenic or endocrine disrupting 

properties applicable to mammals.

C. Aggregate Exposure

1. Dietary exposure. An evaluation of 

chronic dietary exposure to including 

both food and drinking water has been 

performed for the U.S. population and 

various sub-populations including 

infants and children. No acute dietary 

endpoint and dose was identified in the 

toxicology data base for pyriproxyfen, 

therefore, the Agency has concluded 

that there is a reasonable certainty of no 

harm from acute dietary exposure.

i. Food. Chronic dietary exposure to 

pyriproxyfen residues was calculated 

for the U.S.population and 16 

population subgroups assuming 

tolerance level residues, processing 

factors from residue studies, and 100 

percent of the crop treated (PCT). The 

analyses included residue data for all 

existing uses, pending uses, and 

proposed new uses. The results from 

76728 Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 

several representative subgroups are 

listed below. Chronic exposure to the 

overall U.S. population is estimated to 

be 0.0008 mg/kg/bwt day, representing 

0.24% of the RfD. For the most highly 

exposed sub-population, children 1 to 2 

years of age, exposure is calculated to be 

0.0009 mg/kg/bwt day, or 0.26% of the 

RfD in the following Table 1. Generally 

speaking, the Agency has no cause for 

concern if total residue contribution for 

established and proposed tolerances is 

less than 100% of the RfD.

TABLE 1.—CALCULATED CHRONIC DIETARY EXPOSURES TO THE TOTAL U.S. POPULATION AND SELECTED SUBPOPULATIONS TO PYRIPROXYFEN RESIDUES IN FOOD

Population 

Subgroup Exposure (mg/kg/bwt day) Percent of RfD 

Total U.S. 

population 0.00083 0.24

Children (1–2 

years) 0.00091 0.26

Non-nursing 

infants(<1 

year old) 0.00049 0.14

All infants (<1 

year old) 0.00051 0.15

Children (6–

12 years) 0.00044 0.13

Females (13–

49 years) 0.00042 0.12

Nursing Infants (<1 

year old) 0.00023 0.07

ii. Drinking water. Since pyriproxyfen 

is applied outdoors to growing 

agricultural crops, the potential exists 

for pyriproxyfen or its metabolites to 

reach ground surface or surface water 

that may be used for drinking water. 

Because of the physical properties of 

pyriproxyfen, it is unlikely that 

pyriproxyfen or its metabolites can 

leach to potable ground water. To 

quantify potential exposure from 

drinking water, surface water 

concentrations for pyriproxyfen were 

estimated using generic expected 

environmental concentration (GENEEC). 

The peak predicted concentration in 

drinking water was 0.86 part per billion 

(ppb). Using standard assumptions 

about bwt and water consumption, the 

chronic exposure to pyriproxyfen from 

this drinking water would be 0.00009 

mg/kg/day for infants, the most 

sensitive subpopulation. This represents 

0.025% of the RfD (0.35 mg/kg/day) for 

infants. Based on this worse case 

analysis, the contribution of water to the 

dietary risk is negligible.

2. Non-dietary exposure. Pyriproxyfen 

is currently registered for use on 

residential non-food sites. Pyriproxyfen 

is the active ingredient (a.i.) in 

numerous registered products for flea 

and tick control. Formulations include 

foggers, aerosol sprays, emulsifiable 

concentrates, and impregnated materials 

(pet collars). With the exception of the 

pet collar uses, consumer use of 

pyriproxyfen typically results in acute 

and short-term intermittent exposures. 

No acute dermal, or inhalation dose or 

endpoint was identified in the toxicity 

data for pyriproxyfen. Similarly, doses 

and endpoints were not identified for 

short and intermediate term dermal or 

inhalation exposure to pyriproxyfen. 

The Agency has concluded that there 

are reasonable certainties of no harm 

from acute, short term, and intermediate 

term dermal and inhalation 

occupational and residential exposures 

due to the lack of significant 

toxicological effects observed.

Chronic residential post-application 

exposure and risk assessments were 

conducted to estimate the potential risks 

from pet collar uses. The risk 

assessment was conducted using the 

following assumptions: Application rate 

of 0.58 mg/a.i. day (product label), 

average bwt for a 1-6 year old child of 

10 kg, the a.i. dissipates uniformly 

through 365 days (the label instruct to 

change collar once a year), 1% of the a.i. 

is available for dermal and inhalation 

exposure per day (assumption from 

Draft EPA Standard Operating 

Procedures (SOPs) for Residential 

Exposure Assessments, December 18, 

1997). The assessment also assumes an 

absorption rate of 100%. This is a 

conservative assumption since the 

dermal absorption was estimated to be 

10%. The estimated chronic term 

margin of exposure (MOE) was 61,000 

for children, and 430,000 for adults. The 

risk estimates indicate that potential 

risks from pet collar uses do not exceed 

the Agency’s level of concern.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that 

the Agency must consider ‘‘available 

information’’ concerning the cumulative 

effects of a particular pesticide’s 

residues and ‘‘other substances that 

have a common mechanism of toxicity.’’

Available information in this context 

include not only toxicity, chemistry, 

and exposure data, but also scientific 

policies and methodologies for 

understanding common mechanisms of 

toxicity and conducting cumulative risk 

assessments. For most pesticides, 

although the Agency has some 

information in its files that may turn out 

to be helpful in eventually determining 

whether a pesticide shares a common 

mechanism of toxicity with any other 

substances, EPA does not at this time 

have the methodologies to resolve the 

complex scientific issues concerning 

common mechanism of toxicity in a 

meaningful way.

There are no other pesticidal 

compounds that are structurally related 

Federal Register / Vol. 69, No. 245 / Wednesday, December 22, 2004 / Notices 76729

to pyriproxyfen and have similar effects 

on animals. In consideration of potential 

cumulative effects of pyriproxyfen and 

other substances that may have a 

common mechanism of toxicity, there 

are currently no available data or other 

reliable information indicating that any 

toxic effects produced by pyriproxyfen 

would be cumulative with those of other 

chemical compounds. Thus, only the 

potential risks of pyriproxyfen have 

been considered in this assessment of 

aggregate exposure and effects.

Valent will submit information for 

EPA to consider concerning potential 

cumulative effects of pyriproxyfen 

consistent with the schedule established 

by EPA Federal Register of August 4, 

1997 (62 FR 42020) (FRL–5734–6) and 

other subsequent EPA publications 

pursuant to the Food Quality Protection 

Act(FQPA).

E. Safety Determination

1. U.S. population—i. Chronic dietary 

exposure and risk s adult 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/bwt day. The 

estimated chronic dietary exposure from 

food for the overall U.S. population and 

many non-child/infant subgroups is 

from 0.00014 to 0.00042 mg/kg/bwt day, 

0.04 to 0.12% of the RfD. Addition of 

the small but worse case potential 

chronic exposure from drinking water 

(calculated above) increases exposure by 

only 0.00002 mg/kg/bwt day and does 

not change the maximum occupancy of 

the RfD significantly. Generally, the 

Agency has no cause for concern if total 

residue contribution is less than 100% 

of the RfD. It can be concluded that 

there is a reasonable certainty that no 

harm will result to the overall U.S. 

population or any non-child/infant 

subgroups from aggregate, chronic 

dietary exposure to pyriproxyfen 

residues.

ii. Acute dietary exposure and risk s 

adult sub-populations. No acute dietary 

endpoint and dose were identified in 

the toxicology data base for 

pyriproxyfen; therefore, it can be 

concluded that there is a reasonable 

certainty that no harm will result to the 

overall U.S. Population or any nonchild/infant subgroups from aggregate, 

acute dietary exposure to pyriproxyfen 

residues.

iii. Non-dietary exposure and 

aggregate risk s adult sub-populations.

Acute, short term,and intermediate term 

dermal and inhalation risk assessments 

for residential exposure are not required 

due to the lack of significant 

toxicological effects observed. The 

results of a chronic residential postapplication exposure and risk 

assessment for pet collar uses 

demonstrate that potential risks from 

pet collar uses do not exceed the 

Agency’s level of concern. The 

estimated chronic term MOE for adults 

was 430,000.

2. Infants and children—i. Safety 

factor for infants and children. In 

assessing the potential for additional 

sensitivity of infants and children to 

residues of pyriproxyfen, FFDCA 

section 408 provides that EPA shall 

apply an additional margin of safety, up 

to ten-fold, for added protection for 

infants and children in the case of 

threshold effects unless EPA determines 

that a different margin of safety will be 

safe for infants and children.

The toxicological data base for 

evaluating prenatal and postnatal 

toxicity for pyriproxyfen is complete 

with respect to current data 

requirements. There are no special 

prenatal or postnatal toxicity concerns 

for infants and children, based on the 

results of the rat and rabbit 

developmental toxicity studies or the 2-

generation reproductive toxicity study 

in rats. Valent concludes that reliable 

data support use of the standard 100-

fold uncertainty factor and that an 

additional uncertainty factor is not 

needed for pyriproxyfen to be further 

protective of infants and children.

ii. Chronic dietary exposure and risks 

infants and children. Using the 

conservative exposure assumptions 

described above, the percentage of the 

RfD that will be utilized by chronic 

dietary (food only) exposure to residues 

of pyriproxyfen ranges from 0.00023 

mg/kg/bwt day for nursing infants, up to 

0.00091 mg/kg/bwt day for children (1 

to 2 years of age), 0.07 to 0.26% of the 

RfD, respectively. Adding the worse 

case potential incremental exposure to 

infants and children from pyriproxyfen 

in drinking water (0.00009 mg/kg/bwt 

day) does not materially increase the 

aggregate, chronic dietary exposure and 

only increases the occupancy of the RfD 

by 0.009% to 0.010% for children (1 to 

2 years of age). EPA generally has no 

concern for exposures below 100% of 

the RfD because the RfD represents the 

level at or below which daily aggregate 

dietary exposure over a lifetime will not 

pose appreciable risks to human health. 

It can be concluded that there is a 

reasonable certainty that no harm will 

result to infants and children from 

aggregate, chronic dietary exposure to 

pyriproxyfen residues.

iii. Acute dietary exposure and risk s 

infants and children.No acute dietary 

endpoint and dose were identified in 

the toxicology data base for 

pyriproxyfen; therefore, it can be 

concluded that there is a reasonable 

certainty that no harm will result to 

infants and children from aggregate, 

acute dietary exposure to pyriproxyfen 

residues.

iv. Non-dietary exposure and 

aggregate risk s infants and children. 

Acute, short term, and intermediate 

term dermal and inhalation risk 

assessments for residential exposure are 

not required due to the lack of 

significant toxicological effects 

observed. The results of a chronic 

residential post-application exposure 

and risk assessment for pet collar uses 

demonstrate that potential risks from 

pet collar uses do not exceed the 

Agency’s level of concern. The 

estimated chronic term MOE for 

children was 61,000.

F. International Tolerances

There are no presently existing Codex 

MRLs for pyriproxyfen.

[FR Doc. 04–27769 Filed 12–21–04; 8:45 am]

BILLING CODE 6560–50–S

ENVIRONMENTAL PROTECTION 

AGENCY

[OPP–2004–0350; FRL–7684–8]

Pesticide Emergency Exemptions; 

Agency Decisions and State and 

Federal Agency Crisis Declarations

AGENCY: Environmental Protection 

Agency (EPA).

ACTION: Notice.

SUMMARY: EPA has granted or denied 

emergency exemptions under the 

Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) for use of 

pesticides as listed in this notice. The 

exemptions or denials were granted 

during the period July 1, 2004 to 

September 30, 2004 to control unforseen 

pest outbreaks.

FOR FURTHER INFORMATION CONTACT: See 

each emergency exemption or denial for 

the name of a contact person. The 

following information applies to all 

contact persons: Branch Chief, 

Emergency Response Team, Registration 

Division (7505C), Office of Pesticide 

Programs, Environmental Protection 

Agency, 1200 Pennsylvania Ave., NW., 

Washington, DC 20460–0001; telephone 

number: (703) 308–9366.

SUPPLEMENTARY INFORMATION: EPA has 

granted or denied emergency 

exemptions to the following State and 

Federal agencies. The emergency 

exemptions may take the following