[Federal Register Volume 66, Number 65 (Wednesday, April 4, 2001)]
[Notices]
[Pages 17883-17887]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-8140]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1006; FRL-6772-4]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

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

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

[[Page 17884]]


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

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

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

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

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

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-1006 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [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 control number PF-1006. Electronic comments may 
also be filed online at many Federal Depository Libraries.

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

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

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

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

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set

[[Page 17885]]

forth in section 408(d)(2); however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
support granting of the petition. Additional data may be needed before 
EPA rules on the petition.

List of Subjects

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


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

Summary of Petition

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

Interregional Research Project #4 (IR-4)

0E6081

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

A. Residue Chemistry

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

B. Toxicological Profile

    1. Acute toxicity. The acute toxicity of technical grade 
pyriproxyfen is low by all routes, classified as Category III for acute 
inhalation toxicity eye irritation, and Category IV for acute oral and 
dermal toxicity, and skin/eye irritation. Pyriproxyfen is not a skin 
sensitizing agent.
    2. Genotoxicity. Pyriproxyfen was negative in the following tests 
for mutagenicity: Ames assay with and without S9 activation, in vitro 
unscheduled DNA synthesis in HeLa S3 cells, in vitro gene mutation in 
V79 Chinese hamster cells, and in vitro chromosomal aberration with and 
without S9 activation in Chinese hamster ovary cells.
    3. Reproductive and developmental toxicity. In the rat 
developmental toxicity study, maternal toxicity (decreases in food 
consumption, body weight, and body weight gain with increases in water 
consumption was observed at doses of 300 milligrams (mg)/kilogram (kg)/
day and greater, the no observed adverse effect level (NOAEL) for 
prenatal developmental toxicity was 100 mg/kg/day with increased 
incidences of skeletal variations and unspecified visceral variations 
at 1,000 mg/kg/day. A rabbit teratology study resulted in a maternal 
NOAEL of 100 mg/kg/day, with no developmental effects observed in the 
rabbit fetuses.
    In a 2-generation reproduction toxicity study in rats, parental 
toxicity (decreased body weight, weight gain and food consumption in 
both sexes and both generations and increased liver weight in both 
sexes of the F1 generation and liver and kidney histopathology in F1 
males was observed at the highest dose tested (HDT) (5,000 ppm) 
(equivalent to 386 mg/kg/day for males and 442 mg/kg/day for females 
and 519 mg/kg/day for males and 554 mg/kg/day for females F1 
generation.) The parental NOAEL is established at 1,000 ppm and the 
reproductive NOAEL is established at 5,000 ppm.
    4. Subchronic toxicity. Subchronic oral toxicity studies conducted 
with pyriproxyfen technical in the rat, mouse and dog indicate a low 
level of toxicity. Effects observed at high dose levels consisted 
primarily of decreased body weight gain; increased liver weights;

[[Page 17886]]

histopathological changes in the liver and kidney; decreased red blood 
cell counts, hemoglobin and hematocrit; altered blood chemistry 
parameters; and, at 5,000 and 10,000 ppm in mice, a decrease in 
survival rates. The NOAELs from these studies were 400 ppm (23.5 mg/kg/
day for males, 27.7 mg/kg/day for females) in rats, 1,000 ppm (149.4 
mg/kg/day for males, 196.5 mg/kg/day for females) in mice, and 100 mg/
kg/day in dogs.
    5. Chronic toxicity. Pyriproxyfen technical has been tested in 
chronic studies with dogs, rats and mice. Pyriproxyfen technical was 
administered to dogs in capsules at doses of 0, 30, 100, 300 and 1,000 
mg/kg/day for 1-year. Dogs exposed to dose levels of 300 mg/kg/day or 
higher showed decreased weight gain, increased absolute and relative 
liver weight, mild anemia, increased cholesterol and triglycerides in 
both sexes and slight anemia in males. The NOAEL in this study was 100 
mg/kg/day. Pyriproxyfen technical was administered to mice at doses of 
0, 120, 600 and 3,000 ppm in diet for 78-weeks. The NOAEL for systemic 
effects in this study was 600 ppm (84 mg/kg/day in males, 109.5 mg/kg/
day in females), and a lowest observed adverse effect (LOAEL) of 3,000 
ppm (420 mg/kg/day in males, 547 mg/kg/day in females) was established 
based on an increase in kidney lesions.
    In a 2-year study in rats, pyriproxyfen technical was administered 
in the diet at levels of 0, 120, 600, and 3,000 ppm. The NOAEL for 
systemic effects in this study was 600 ppm (27.31 mg/kg/day in males, 
35.1 mg/kg/day in females). A LOAEL of 3,000 ppm (138 mg/kg/day in 
males, 182.7 mg/kg/day in females) was established based on a 
depression in body weight gain in females.
    6. Animal metabolism. The absorption, tissue distribution, 
metabolism and excretion of 14C-labeled pyriproxyfen were 
studied in rats after single oral doses of 2 or 1,000 mg/kg bw 
(phenoxyphenyl and pyridyl label), and after a single oral dose of 2 
mg/kg bw (phenoxyphenyl label only) following 14 daily oral doses at 2 
mg/kg bw of unlabelled material. For all dose groups, most (88-96%) of 
the administered radiolabel was excreted in the urine and feces within 
two days after radiolabeled test material dosing, and 92-98% of the 
administered dose was excreted within seven days. Seven days after 
dosing, tissue residues were generally low, accounting for no more than 
0.3% of the dosed 14C. Radiocarbon concentrations in fat 
were the highest in tissues analyzed. Recovery in tissues over time 
indicates that the potential for bioaccumulation is minimal. There were 
no significant sex or dose-related differences in excretion or 
metabolism.
    7. Endocrine disruption. Pyriproxyfen is specifically designed to 
be an insect growth regulator and is known to produce juvenoid effects 
on arthropod development. However, according to Valent this mechanism-
of-action in target insects and other some arthropods has no relevance 
to any mammalian endocrine system. While specific tests, uniquely 
designed to evaluate the potential effects of pyriproxyfen on mammalian 
endocrine systems have not been conducted, the toxicology of 
pyriproxyfen has been extensively evaluated in acute, sub-chronic, 
chronic, developmental, and reproductive toxicology studies including 
detailed histopathology of numerous tissues. The results of these 
studies show no evidence of any endocrine-mediated effects and no 
pathology of the endocrine organs. Consequently, Valent concludes that 
pyriproxyfen does not possess estrogenic or endocrine disrupting 
properties applicable to mammals.
    8. Neurotoxicity. Neither neurotoxic symptoms nor any other 
indication of neurotoxicity has been observed in any of the acute, 
subchronic, chronic, developmental, or reproductive studies performed 
with pyriproxyfen.
    9. Toxicological endpoints. EPA has established a reference dose 
(RfD) for pyriproxyfen of 0.35 mg/kg bw/day, based on the NOAEL from 
the rat 2-year chronic/carcinogenicity study and a safety factor of 
100. However, the Agency has not yet identified acute or short term 
toxicity endpoints of concern for oral, inhalation, or dermal exposure. 
Pyriproxyfen is classified as Category E: Not carcinogenic in two 
acceptable animal studies.

C. Aggregate Exposure

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

[[Page 17887]]

D. Cumulative Effects

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

E. Safety Determination

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

F. International Tolerances

    There are no Codex MRLs for pyriproxyfen.
[FR Doc. 01-8140 Filed 4-3-01;8:45 am]
BILLING CODE 6560-50-S