[Federal Register Volume 67, Number 224 (Wednesday, November 20, 2002)]
[Notices]
[Pages 70073-70079]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-29330]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2002-0126; FRL-7184-7]


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 ID number OPP-2002-0126, must be 
received on or before December 20, 2002.

ADDRESSESS: 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. To ensure proper 
receipt by EPA, it is imperative that you identify docket ID number 
OPP-2002-0126 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller, 
Registration Division, Office of Pesticide Programs, (7505C) 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-6224; 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
                                                       productionmption
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------


[[Page 70074]]

    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. To determine 
whether you or your business may be affected by this action, you should 
examine the applicability provisions in OPP-2002-0126. 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 Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2002-0126. 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, 
1921 Jefferson Davis Hwy., 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. 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 
feasable, 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.1. EPA intends to work 
towards providing electronic access to all of the publicly available 
docket materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or 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 is 
otherwise protected by statute, please follow the instructions in Unit 
I.D. Do not use EPA Dockets or e-mail to submit CBI or information 
protected by statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any indentifying 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-2002-0126. 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 [email protected], 
Attention: Docket ID Number OPP-2002-0126. In contrast to EPA's 
electronic public docket, EPA's email 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

[[Page 70075]]

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-2002-0126.
    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, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket 
ID Number OPP-2002-0126. 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 ckearly 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. Offer alternative ways to improve the notice or collection 
activity.
    7. Make sure to submit your comments by the deadline in this 
document.
    8. 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 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, Pesticides and pests.

    Dated: October 27, 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 Nichino America Incorporated, and represents 
the view of Nichino America Incorporated. 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.

Nichino America Incorporated

PP 1F6428

    EPA has received a pesticide petition (1F6428) from Nichino America 
Incorporated, 4550 New Linden Hill Road, Suite 501, Wilmington, DE 
19808 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 
346a(d), to amend 40 CFR part 180, by establishing a tolerances for 
combined residues of pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-
difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetate) and its 
acid metabolite, E-1, (2-chloro-5-(4-chloro-5-difluoromethoxy-1-
methylpyrazol-3-yl)-4-fluorophenoxyacetic acid) expressed as the ester 
equivalent in or on the raw agricultural commodities (RACs) derived 
from cotton; undelinted seed at 0.05 parts per million (ppm); and gin 
byproducts at 1.5 ppm; in or on the RAC potato at 0.02 ppm; in or on 
the RACs corn grain, corn stover, corn forage, soybean seed, soybean 
forage, and soybean hay at 0.01 ppm; wheat forage, wheat hay, wheat 
straw, and wheat grain at 0.01 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. The qualitative nature of the residues of 
pyraflufen-ethyl (ET-751) in cotton, potatoes, corn, soybeans, and 
wheat is adequately understood. The metabolism of pyraflufen-ethyl has 
been studied in cotton, wheat, and potato. Metabolism in the plant 
involves ester hydrolysis, de-methylation on the pyrazole ring and 
further degradation of the phenoyxyacetate moiety to bound polar 
metabolites. The nature of the residue is adequately understood and the 
residues of concern are the parent, pyraflufen-ethyl, and the acid 
metabolite, E-1, only.
    2. Analytical method. The enforcement analytical method utilizes 
gas chromatography/mass spectrophotometry with selected ion monitoring 
for detecting and measuring levels of pyraflufen-ethyl and the acid 
metabolite with a general limit of quantification (LOQ) of 0.02 ppm 
(combined E-1 and parent). This method allows detection of residues at 
or above the proposed tolerances. The method has undergone independent 
laboratory validation as required by PR Notices 88-5 and 96-1.
    3. Magnitude of residues in crops--i. Potato. No apparent residues 
of pyraflufen-ethyl were observed in potato at or above 0.02 ppm (the 
LOQ

[[Page 70076]]

for the analytical method). The field studies, conducted at 3x the 
highest intended label use rate, in 16 trials in 11 states, clearly 
support the proposed tolerances of 0.02 ppm (combined E-1 and parent). 
No detectable residues of parent or the acid metabolite were observed 
in any processed potato fraction at 5x the maximum proposed application 
rate and proposed pre-harvest interval (PHI) in a field study, with the 
LOQ of 0.02 ppm (combined E-1 and parent). The tolerance that is being 
proposed for the use of pyraflufen-ethyl plus the acid metabolite on 
potato is 0.02 ppm.
    ii. Cotton. Twelve field residue trials were conducted in seven 
different states. Applications in the trials were 3x the proposed label 
directions for use and at the proposed PHI of 7 days. Analysis of the 
treated samples showed that the residues of pyraflufen-ethyl (ethyl 2-
chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-
fluorophenoxyacetate) plus its acid metabolite, E-1, (2-chloro-5-(4-
chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetic 
acid) expressed as the ester equivalent at the exaggerated rate, were 
below the proposed tolerance of 0.05 ppm in cotton seed at the proposed 
labeled PHI in all samples. No residues were seen in the processed 
fractions of meal, hull, and oil, when one trial was run in a typical 
cotton growing area. The application rate for this processing study was 
15x the maximum proposed application rate and at the proposed PHI. This 
indicates that there is no concentration of pyraflufen-ethyl (ethyl 2-
chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-
fluorophenoxyacetate) plus its acid metabolite, E-1, (2-chloro-5-(4-
chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetic 
acid), expressed as the ester equivalent in any of the processed 
fractions. Low residues seen in the undelinted cottonseed were 
consistent with the magnitude of residue trials. Combined residues of 
pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-difluoromethoxy-1-
methylpyrazol-3-yl)-4-fluorophenoxyacetate) plus its acid metabolite, 
E-1 (2-chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-
fluorophenoxyacetic acid) in cotton gin byproducts from applications at 
3x the proposed application rate ranged from 0.125 ppm to 1.314 ppm, 
and averaged 0.035 ppm from applications made at 1x the proposed 
application rate. The proposed tolerance of 0.05 ppm for pyraflufen-
ethyl (ethyl 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-
yl)-fluorophenoxyacetate) plus its acid metabolite, E-1, (2-chloro-5-
(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetic 
acid) in cotton seed and 1.5 ppm in cotton gin byproducts are supported 
by the field residue data.
    iii. Corn. Three exaggerated rate residue trials were conducted in 
three different states on different soil types. Applications in the 
trials were 5x to 10x the proposed label directions for use as a pre-
plant burndown herbicide. Analysis of the treated samples showed zero 
residues of pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-
difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetate) plus its 
acid metabolite, E-1, (2-chloro-5-(4-chloro-5-difluoromethoxy-1-
methylpyrazol-3-yl)-4-fluorophenoxyacetic acid) expressed as the ester 
equivalent at the exaggerated rate. The LOQ for the parent and the 
metabolite was 0.005 ppm in each case. Since no residues were observed 
at exaggerated rates in RACs, no processing studies were conducted.
    iv. Soybean. Three exaggerated rate residue trials were conducted 
in three different states on different soil types. Applications in the 
trials were 5x to 10x the proposed label directions for use as a pre-
plant burndown herbicide. Analysis of the treated samples showed zero 
residues of pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-
difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetate) plus its 
acid metabolite, E-1, (2-chloro-5-(4-chloro-5-difluoromethoxy-1-
methylpyrazol-3-yl)-4-fluorophenoxyacetic acid) expressed as the ester 
equivalent at the exaggerated rate. The LOQ for the parent and the 
metabolite was 0.005 ppm in each case. Since no residues were observed 
at exaggerated rates in RACs, no processing studies were conducted.
    v. Wheat. Three exaggerated rate residue trials were conducted in 
three different states on different soil types. Applications in the 
trials were 5x to 10x the proposed label directions for use as a pre-
plant burndown herbicide. Analysis of the treated samples showed zero 
residues of pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-
difluoromethoxy-1-methylpyrazol-3-yl)-4-fluorophenoxyacetate) plus its 
acid metabolite, E-1, (2-chloro-5-(4-chloro-5-difluoromethoxy-1-
methylpyrazol-3-yl)-4-fluorophenoxyacetic acid) expressed as the ester 
equivalent at the exaggerated rate. The LOQ for the parent and the 
metabolite was 0.005 ppm in each case. Since no residues were observed 
at exaggerated rates in RACs, no processing studies were conducted.
    4. Magnitude of the residue in animals.--i. Ruminants. The maximum 
dietary burden in beef and dairy cows results from a diet comprised of 
undelinted cottonseed, cotton meal, cotton hulls, cotton gin 
byproducts, potato culls, potato waste, and from grain (seed), forage, 
hay, stover (fodder), silage, meal, hulls, straw, aspirated grain 
fractions, and milled byproducts of corn, soybeans, and wheat for a 
total dietary burden that is significantly lower than levels that would 
require the proposal of tolerances in ruminants. This conclusion is 
based on exaggerated rate animal metabolism studies carried out on 
pyraflufen-ethyl and its significant metabolites. Therefore, an 
exemption from tolerances in milk, meat, and meat by-products under 40 
CFR 180.6(a)(3) and (b) is proposed as it is not possible to establish 
with certainty whether finite residues will be incurred, but there is 
no reasonable expectation of finite residues.
    ii. Poultry. The maximum poultry dietary burden results from a diet 
comprised of cotton meal, corn grain, corn milled byproducts, soybean 
seed, soybean meal, soybean hulls, wheat grain, and wheat milled 
byproducts for a total dietary burden that is significantly lower than 
the levels that would require the proposal of tolerances in poultry. 
This conclusion is based on the exaggerated rate metabolism studies 
carried out on pyraflufen-ethyl and its acid metabolite. Therefore, an 
exemption from tolerances in poultry meat, meat byproducts, fat, and 
eggs under 40 CFR 180.6(a)(3) and (b) is proposed as it is not possible 
to establish with certainty whether finite residues will be incurred, 
but there is no reasonable expectation of finite residues.

B. Toxicological Profile

    1. Acute toxicity. Pyraflufen-ethyl technical is considered to be 
nontoxic (toxicity category IV) to the rat by the oral route of 
exposure. In an acute oral toxicity study conducted in rats, the oral 
LD50 value for technical pyraflufen-ethyl was determined to 
be >5,000 milligrams/kilograms body weight (mg/kg bwt). The results 
from the acute dermal toxicity study in rabbits indicate that 
pyraflufen-ethyl is slightly toxic (toxicity category III) to rabbits 
by the dermal route of exposure. The dermal LD50 value of 
technical pyraflufen-ethyl was determined to be >2,000 mg/kg for both 
male and female rabbits. Pyraflufen-ethyl technical is considered to be 
nontoxic (toxicity category IV) to the rat by the respiratory route of 
exposure. Inhalation exposure of rats to pyraflufen-ethyl technical 
resulted in an

[[Page 70077]]

LC50 >5.53 milligrams/Liter (mg/L) (analytical) for both 
males and females. Pyraflufen-ethyl technical was shown to be non-
irritating to rabbit skin (toxicity category IV). Pyraflufen-ethyl 
technical was shown to be slightly irritating to rabbit eyes (toxicity 
category III). Application of technical material to the rabbit eye 
resulted in iris and conjunctival irritation from 1 to 24 hours, which 
was clear by 72 hours. Based on the results of a dermal sensitization 
study, pyraflufen-ethyl technical is not considered a sensitizer in 
guinea pigs.
    2. Genotoxicity. Pyraflufen-ethyl technical was not mutagenic in 
any of the following genotoxicity studies. Point mutations in bacteria 
in an Ames study with Salmonella typhimurium, and Escherichia coli; 
negative in chromosome aberrations in vitro human lymphocytes, and in 
the mouse micronucleus; negative for DNA repair in in vitro and in vivo 
rat liver hepatocyte assays and Bacillus subtillis. For mammalian gene 
mutation, in one in vitro mouse lymphoma mutation assay, no evidence of 
mutagenicity was seen in the absence of metabolic activation. With S9 
activation at levels up to 200 [igrave]g/Liter, equivocal results were 
seen. The study report provided no criteria for positive or negative 
responses. When this in vitro study was repeated, no positive or 
equivocal results in the presence of activation with S9 at levels of S9 
up to 350 [igrave]g/Liter were seen. These levels of activation were 
greater than those tested in the earlier study and both small and large 
colonies were counted. The overall weight of evidence indicates that 
pyraflufen-ethyl is not genotoxic.
    3. Reproductive and developmental toxicity. The developmental 
toxicity study in rats conducted with pyraflufen-ethyl technical showed 
no evidence of teratogenic effects in fetuses and no evidence of 
developmental toxicity. Thus, pyraflufen-ethyl is neither a 
developmental toxicant nor a teratogen in the rat. Pyraflufen-ethyl was 
administered by gavage during gestation and showed no adverse effects 
on dams or fetuses at dose levels of 0, 100, 300, up to and including a 
limit dose of 1,000 mg/kg/day. The maternal and developmental toxicity 
no observe adverse effects (NOAELs) were both >1,000 mg/kg/day. Results 
from a developmental toxicity study in rabbits conducted with 
pyrafluflen-ethyl technical also indicated no evidence of 
teratogenicity or developmental toxicity. Thus, pyraflufen-ethyl 
technical is neither a developmental toxicant nor a teratogen in the 
rabbit. Rabbits fed pyraflufen-ethyl at 0, 20, 60, or 150 mg/kg/day, 
resulted in severe maternal toxicity, including lethality, from 
gastrointestinal irritation at doses of 60 and 150 mg/kg/day. The 
maternal NOAEL was 20 mg/kg/day. The NOAEL for the offspring was 60 mg/
kg/day, based on increased post-implantation loss observed at 150 mg/
kg/day. Neither the rat nor the rabbit developmental study showed 
evidence of unique fetal susceptibility to pyraflufen-ethyl.
    In a multigeneration rat reproduction study conducted at dietary 
concentrations of 0, 100, 1,000 and 10,000 ppm, pyraflufen-ethyl had no 
effect on reproductive parameters, including mating indices, fertility 
index, gestation index, duration of gestation, numbers of implantation 
sites, numbers and morphology of epididymal sperm, and estrous cycle at 
any dose level. Reproductive performance was not affected by 
pyraflufen-ethyl at the highest dose level of 10,000 ppm (male 721 to 
844 mg/kg/day and female 813 to 901 mg/kg/day). The pup NOAEL was 1,000 
ppm, based on decreased body weight in the F1 and F2 male and female 
pups on day 17 at the 10,000 ppm dose level. Results from the 
reproduction study and the developmental toxicity studies conducted 
with pyraflufen-ethyl technical show no increased sensitivity to 
developing offspring as compared to parental animals, because the 
NOAELs for growth and development of offspring were equal to or greater 
than the NOAELs for parental or maternal toxicity.
    4. Subchronic toxicity. A short-term (28-day) dermal study in 
rabbits was conducted with pyraflufen-ethyl technical. Pyraflufen-ethyl 
was administered dermally to rats for 28 days at dose levels of 0, 300, 
and 1000 mg/kg day. Slight, transient erythema was observed during week 
3 in 3 treated males. This finding was not dose-related, was not 
considered to be adverse, and the relationship to the test material 
administration was unclear. The NOAEL was considered to be 1,000 mg/kg/
day. A 90-day rat feeding study was conducted at dose levels of 0, 200, 
1,000, 5,000, or 15,000 ppm pyraflufen-ethyl. The NOAEL in this study 
was considered to be 1,000 ppm (85.6 mg/kg/day for males and 95.4 mg/
kg/day for females), based on slightly increased phosphorous 
concentrations in females and hepatocytic hypertrophy in males at 5,000 
ppm. In addition, the highest dose of 15,000 ppm resulted in erythocyte 
toxicity, mitochondrial changes in the hepatocytes and the presence of 
Kupffer cells. Also, at the high dose level increased kidney weights in 
males and increased absolute and relative spleen weights in both sexes 
were observed.
    In a 90-day oral toxicity study in dogs, pyraflufen-ethyl was 
administered via capsule at dose levels of 0, 40, 200, and 1,000 mg/kg/
day. No treatment-related findings were observed and the NOAEL was 
determined to be >1,000 mg/kg/day. At the limit dose, no effects in 
body weight or organ weights, clinical chemistry, hematology, 
histopathology, and gross pathology were observed. To determine whether 
the test material was absorbed or not, plasma was collected 1-hour 
after administration of pyraflufen-ethyl during week 13. The detection 
of 2 major degradation products, E-1 and E-9, confirmed the adsorption 
and gastrointestinal and systemic exposure to pyraflufen-ethyl.
    5. Chronic toxicity. A 1-year chronic dog study was conducted in 
Beagle dogs, with pyraflufen-ethyl administered orally by gelatin 
capsule at doses of 0, 40, 200, and 1,000 mg/kg/day. There were no 
mortalities and no clinical signs of toxicity. No treatment-related 
effects were noted on body weights, food consumption, hematology and 
clinical chemistry parameters, urinalysis, ophthmoscopy, and organ 
weights. No macrosopic or microscopic lesions were noted. The NOAEL was 
>1,000 mg/kg/day.
    In a 2-year chronic toxicity/oncogenicity study, pyraflufen-ethyl 
was administered to CD rats at dietary levels of 0, 80, 400, 2,000, or 
10,000 ppm (equivalent to 0, 3.4, 17.2, 86.7, and 468.1 mg/kg/day for 
males and 0, 4.4, 21.8, 111.5, and 578.5 mg/kg/day for females). 
Mortality was unaffected by treatment. Body weight gain was 
statistically significantly depressed for those rats fed 10,000 ppm at 
1-year compared to the control. Treatment-related histopathology was 
seen in the kidney, liver, and bile duct at 10, 000 ppm. At 2,000 and 
10,000 ppm, vacuoles within the mitochondria of centriacinar and 
periacinar hepatocytes were seen. Effects on urine volume, urine 
specific gravity, and kidney weights were seen at 2,000 ppm in males. 
The NOAEL was 17.2 mg/kg/day for males and 21.8 mg/kg/day for females. 
No evidence of carcinogenicity was observed.
    In a 78-week carcinogenicity study, mice were fed pyraflufen-ethyl 
in the diet at levels of 0, 200, 1,000, or 5,000 ppm (equivalent to 0, 
21, 110, 547 mg/kg/day for males and 0. 20, 98, 524 mg/kg/day for 
females). An maximum tolerance dose (MTD) was reached at 1,000 ppm, 
based on increased liver weight and liver histopathological changes 
(including necrosis) seen at this

[[Page 70078]]

feeding level. In the highest dose group, effects of pyraflufen-ethyl 
on hematological parameters were observed. The incidence of 
hepatocellular adenoma was increased in animals receiving 5,000 ppm, 
compared to controls. This benign tumor was likely induced by the 
adaptive response to the hepatocellular degeneration and not as a 
result of any genotoxic potential of pyraflufen-ethyl. In addition the 
response was observed only at a dose level that was in excess of an 
MTD.
    6. Animal metabolism. The qualitative nature of the residues of 
pyraflufen-ethyl and its acid metabolite, E-1, in animals is adequately 
understood. Pyraflufen-ethyl is rapidly absorbed, metabolized, and 
excreted to feces and urine, with greater than 90% of the administered 
dose excreted within 24 hours in rats. Based on metabolism studies with 
goats, hens, and rats, there is no reasonable expectation that 
measurable pyraflufen-ethyl-related residues will occur in meat, milk, 
poultry, or eggs from the proposed use.
    7. Metabolite toxicology. No toxicologically significant 
metabolites were detected in plant or animal metabolism studies for 
cotton or potatoes.
    8. Endocrine disruption. Chronic, lifespan, and multigenerational 
bioassays in mammals and acute and subchronic studies on aquatic 
organisms and wildlife did not reveal any endocrine effects for 
pyraflufen-ethyl. Any endocrine related effects would have been 
detected in this comprehensive series of required tests. The 
probability of any such effect due to agricultural uses of pyraflufen-
ethyl is negligible.

C. Aggregate Exposure

    1. Dietary exposure. The potential dietary exposure to pyraflufen-
ethyl has been calculated from the proposed tolerances for use on 
cotton, and potato. While tolerances at the LOQ are proposed for corn, 
soybean, and wheat, it is concluded that there is no potential for 
residues in these crops and thus no dietary exposure. These very 
conservative chronic dietary exposure estimates used the tolerance 
value for all the raw agricultural commodities. In addition these 
estimates assume that 100% of the cotton and potato crops contain 
pyraflufen-ethyl residues.
    i. Food. The chronic population adjusted dose (cPAD) for the 
general population, based on residues at the tolerance levels and 100% 
of potato and cotton crops treated is expected to be approximately 
0.000020 mg/kg bwt/day or <0.1% of the reference dose (RFD) ( 0.172 mg/
kg/day). Of the standard subgroups analyzed by the dietary exposure 
evaluation model (DEEM), the subgroup with the highest exposures are 
children ages 1 to 6 years, with a cPAD of 0.000041 mg/kg/day or less 
than 0.1% of the RfD mg/kg/day. With children ages 7 to 12 with 
exposures of 0.000027 mg/kg/day, the exposure is less than 0.1% of the 
RfD.
    ii. Drinking water. As a screening level assessment for aggregate 
exposure, EPA evaluates drinking water level of comparison (DWLOC), 
which is the maximum concentration of a chemical in drinking water that 
would be acceptable in terms of total aggregate exposure to that 
chemical. Based on the chronic RFD of 0.172 mg/kg/day, based on the 
NOAEL of 17.2 mg/kg/day observed in the chronic rat feeding study and 
an uncertainty factor (UF) of 100, and EPA's default factors for body 
weight and drinking water consumption, the DWLOCs have been calculated 
to assess the potential dietary exposure from residues of pyraflufen-
ethyl and the acid metabolite, E-1, in water. For the adult population, 
the chronic DWLOC was 35,086 parts per billion (ppb) for the U.S. 
population, and for children 10,172 ppb.
    Chronic drinking water exposure analyses were calculated using EPA 
screening models, screening concentration in ground water (SCI-GROW) 
for ground water and generic expected environmental concentration 
(GENEEC) for surface water). The calculated peak GENEEC value for the 
acid metabolite, E-1, the major degradation of pyraflufen-ethyl which 
is formed within an hour of addition to a water solution or to soil, is 
0.3321 ppb and the SCI-GROW value is 0.00024 ppb. These values are very 
conservative estimates compared to the values derived from the parent. 
Nonetheless, for the U.S. adult population, the estimated exposures of 
the E-1 acid metabolite in surface water and ground water are 
approximately 0.00094% and 0.0000007%, respectively, of the DWLOC. For 
children, the estimated exposures of the acid metabolite in surface 
water and ground water are approximately 0.0033% and 0.000002%, 
respectively of the DWLOC. Therefore, the exposures to drinking water 
from the acid metabolite are negligible. Based on the dietary and 
drinking water assessments, aggregate exposure to residues of 
pyraflufen-ethyl and the acid metabolite in food and water can be 
considered to be negligible.
    2. Non-dietary exposure. It is being proposed that pyraflufen-ethyl 
be registered in the following non-food sites: airports, commercial 
plants, fence lines, farmyards, and farm buildings; storage and lumber 
yards; barrier strips and firebreaks; equipment areas, nurseries and 
ornamental plantings; established ornamental turf; railroad, roadside, 
and utility rights-of-ways; dry ditches and ditch banks; fuel tank 
farms and pumping stations; other similar non-crop areas. Exposure to 
pyraflufen-ethyl for the mixer/loader/groundboom/ aerial applicator was 
calculated using the Pesticides Handlers Exposure Database (PHED). 
These PHED assessments were based on a 70 kg operator treating 80 acres 
per day using ground boom equipment on both cotton and potato fields; 
an operator treating 1,200 acres per day using aerial equipment on 
cotton fields; and an operator treating 350 acres per day using aerial 
equipment on potato fields (EPA, 1999) at a maximum use rate of 0.009 
pounds active ingredient per acre for potato and 0.0045 pounds active 
ingredient per acre for cotton. All workers were assumed to be wearing 
long pants and long-sleeved shirts. Mixer-loaders were assumed to be 
wearing gloves, while aerial and ground applicators and flaggers were 
not assumed to be wearing gloves. Margins of exposure (MOE) for acute 
and short-term exposure were calculated utilizing a dermal and 
inhalation NOAEL of 20 mg/kg/day, based on maternal toxicity seen in 
the rabbit teratology study at 60 mg/kg/day, and assuming 100% dermal 
absorption. MOEs for intermediate-term exposure were calculated 
utilizing a dermal endpoint of 250 mg/kg/day, the systemic NOAEL from 
the 28-day dermal toxicity study in the rat with the 2.5% EC 
formulation. This was the highest dose level in the study and no 
systemic effects were seen at this dose level. For the acute inhalation 
endpoint we used 86 mg/kg/day, based on a NOAEL of 1,000 ppm or 85.6 
mg/kg/day in males in the 90-day oral feeding study in the rat. The 
combined MOE (inhalation plus dermal) for pyraflufen-ethyl was greater 
than 4,900 for acute and short-term exposure, while the intermediate-
term total MOEs were all greater than 56,000. The results indicate that 
large margins of safety exist for the proposed uses of pyraflufen-
ethyl.

D. Cumulative Effects

    Pyraflufen-ethyl belongs to the protox inhibitor class of 
compounds, and chemically is a 3-phenylpyrazole. The herbicidal 
activity of protox inhibitors is due to the inhibition of 
protoporphyrinogen IX oxidase. All relevant toxicological data has been 
provided to EPA. Chemicals with a similar mode of action, i.e., the 
protox inhibitors, have different chemical

[[Page 70079]]

structures compared to pyraflufen-ethyl. Although other protox 
inhibitors have a similar herbicidal mode of action, there is no 
information available to suggest that these compounds exhibit a similar 
toxicity profile in the mammalian system. We are aware of no 
information to indicate or suggest that pyraflufen-ethyl has any toxic 
effects on mammals that would be cumulative with those of any other 
chemical. Since pyraflufen-ethyl is relatively non-toxic, cumulative 
effects of residues and other compounds are not anticipated. Therefore, 
for the purposes of this Food Quality Protection Act (FQPA) document, 
there should be no consideration of cumulative risk that would require 
assessment.

E. Safety Determination

    1. U.S. population. Based on the chronic toxicity data, the RfD for 
pyraflufen-ethyl is considered to be 0.172 mg/kg/day. This value is 
based on the NOAEL of 17.2 mg/kg/day observed in the chronic rat 
feeding study and a safety (uncertainty) factor of 100, the worse case 
estimate of chronic dietary exposure of pyraflufen-ethyl from cotton, 
potatoes, corn, or soybean will utilize less than 0.1% of the RfD for 
the general U.S. population. 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. The complete and reliable toxicity 
data and the conservative chronic exposure assumptions support the 
conclusion that there is a reasonable certainty of no harm from dietary 
(food) exposure to pyraflufen-ethyl and the acid metabolite residues. 
Moreover, as exposure to residues of pyraflufen-ethyl and the acid 
metabolite via water is negligible, there is a reasonable certainty of 
no harm from aggregate exposure to pyraflufen-ethyl and the acid 
metabolite residues.
    2. Infants and children. The conservative estimates, as described 
above, indicate that chronic dietary exposure of pyraflufen-ethyl and 
the acid metabolite from cotton and potato will utilize less than 0.1% 
of the RfD for non-nursing infants, less than 0.1% of the RfD for 
children ages 1 to 6; and less than 0.1% of the RfD for all populations 
examined. No developmental, reproductive, or fetotoxic effects were 
noted at the highest doses of pyraflufen-ethyl tested in guideline 
reproductive or developmental toxicity studies. Based on the current 
toxicological data requirements, the data base relative to prenatal and 
postnatal effects for children is complete, valid and reliable. Results 
from the teratology studies and the 2-generation reproduction study 
support NOAELs for fetal/developmental effects or reproductive/
offspring effects, respectively, equivalent to the highest 
concentrations tested. As such, there is no increased sensitivity of 
infants and children to residues of pyraflufen-ethyl. Therefore, an 
additional safety (uncertainty) factor is not warranted, and the RfD of 
0.172 mg/kg/day, which utilizes a 100-fold safety factor, is 
appropriate to assure a reasonable certainty of no harm to infants and 
children.

F. International Tolerances

    There is no Codex maximum residue level established for residues of 
pyraflufen-ethyl and the acid metabolite on any crops.
[FR Doc. 02-29330 Filed 11-19-02; 8:45 am]
BILLING CODE 6560-50-S