[Federal Register Volume 69, Number 164 (Wednesday, August 25, 2004)]
[Notices]
[Pages 52256-52261]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-19441]


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ENVIROMENTAL PROTECTION AGENCY

[OPP-2004-0245; FRL-7372-4]


Quizalofop-Ethyl; 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 identification (ID) number OPP-
2004-0245, must be received on or before September 24, 2004.

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:  James A. Tompkins, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-5697; e-mail address: 
[email protected].

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 code 111)
     Animal production (NAICS code 112)
     Food manufacturing (NAICS code 311)
     Pesticide manufacturing (NAICS code 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-2004-0245. 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.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

[[Page 52257]]

not use EPA Dockets or e-mail to submit CBI or information protected by 
statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also, include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at 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-2004-0245. 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-2004-0245. 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-2004-0245.
    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-2004-0245. 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 assigned to this action in the subject line on the first page 
of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

     EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in FFDCA section 408(d)(2); however, 
EPA has not fully evaluated the sufficiency of the submitted data at 
this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

List of Subjects

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


    Dated: August 16, 2004.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

     The petitioner's summary of the pesticide petition is printed 
below as required by FFDCA section 408(d)(3). The summary of the 
petition was prepared by E.I. du Pont de Nemours and Company 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.

 E.I. du Pont de Nemours and Company

 PP 3F4268

     EPA has received additional residue studies required by the Agency 
in support of a pesticide petition PP 3F4268 from E. I. du Pont de 
Nemours and Company, DuPont Crop Protection,

[[Page 52258]]

Laurel Run, Wilmington, DE 19880-0038 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 180.441(a)(1) by establishing tolerances for 
residues of quizalofop (2-[4-(6-chloroquinoxalin-2yl)oxy)phenoxy])-
propanoic acid], and quizalofop ethyl [ethyl-2-[4-(6-chloroquinoaxalin-
2yl)oxy)phenoxy)propanoate), all expressed as quizalofop ethyl (DUPONT 
ASSURE II) in or on the raw agricultural commodities, dry beans at 0.4 
parts per million (ppm), dry bean straw at 3.0 ppm, succulent beans at 
0.25 ppm, succulent bean forage at 3.0 ppm, dry peas at 0.25 ppm, dry 
pea straw at 3.0 ppm, succulent peas at 0.3 ppm, succulent pea forage 
at 3.0 ppm, sugar beet root at 0.1 ppm, sugar beet top at 0.5 ppm; and 
paragraph (a) (3) by establishing a permanent tolerance for quizalofop 
p-ethyl for sugar beet molasses at 0.2 ppm. These proposed permanent 
tolerances will replace the time-limited tolerances listed in paragraph 
(a) (4). This summary was prepared by the petitioner. EPA has 
determined that the 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 the petition. Additional data may be 
needed before EPA rules in the petition. The additional residue studies 
were required by the Agency upon issuance of the time-limited 
tolerances, which published in the Federal Register of June 14, 1996 
(61 FR 30171) (FRL-5375-6).

A. Residue Chemistry

    1. Plant metabolism. The registrant has provided plant metabolism 
studies for cotton, potatoes, soybeans, sugar beets, and tomatoes. 
These studies have been previously reviewed in PP 3F4268. In summary, 
quizalofop-p ethyl ester is metabolized by cleavage at three sites as 
follows:
    i. Primary pathway is hydrolysis of the ethyl ester to form the 
quizalofop-p acid.
    ii. Cleavage of the enol ether linkage in the acid, between the 
phenyl and quinoxalinyl rings, to form phenols.
    iii. Cleavage of the ether linkage between the isopropanic group 
and the phenyl ring to form a phenol.
     The plant metabolism data show that quizalofop-p ethyl ester does 
not translocate, but is rapidly hydrolyzed to the corresponding acid; 
then the phenols conjugate with the plant sugars. Metabolism studies in 
soybeans using the racemic mixture quizalofop ethyl ester and the 
resolved D+ isomer show nearly identical pathways.
     The nature of the quizalofop-p ethyl ester residue in cottonseed, 
potatoes, tomatoes, soybeans, and sugar beets is adequately understood. 
The residues of concern are quizalofop-p ethyl ester and its acid 
metabolite, quizalofop-p, and the S enantiomers of both the ester and 
the acid, all expressed as quizalofop-p ethyl ester.
    2. Analytical method. An adequate analytical methodology (high-
pressure liquid chromatography using either ultraviolet or fluorescence 
detection) is available for enforcement purposes in Vol. II of the Food 
and Drug Administration Pesticide Analytical Method (PAM II, Method I). 
There are currently no actions pending against the registration of this 
chemical. Any secondary residues expected to occur in eggs; meat, fat, 
and meat byproducts of cattle, goats, hogs, horses, sheep, and poultry; 
and milk from this use will be covered by existing tolerances.
     Adequately validated residue analytical method, DuPont 2829 (Xenos 
Method XAM-38A, Determination of Quizalofop-P-Ethyl and its Metabolites 
in Canola, Flax, Lentils, Peas, Dry and Succulent Beans and Sugar Beet 
Tops and Roots, by Liquid Chromatography). This method determines 
residues of quizalofop-P-ethyl and its metabolites in oilseed and other 
crops. It measures levels of quizalofop-P-ethyl, quizalofop-P acid and 
conjugates as total residues in the form of 2methoxy-6-
chloroquinoxaline (MeCHQ). Quantitation was carried out using normal 
phase high pressure liquid chromatography with fluorescence detection. 
The residues were expressed as equivalents of quizalofop-P-ethyl.
     A successful tolerance method validation (TMV) on DuPont 2829 
(Xenos Method XAM-38A) is not a prerequisite for a tolerance on beans 
(succulent and dried) as well as sugar beets and sugar beet molasses as 
there is already an enforcement method in PAM II.
    3. Magnitude of residues--a. Magnitude of the residue in plants. 
The studies submitted include field trials in three regions for 
succulent beans, six additional sites for dry beans in four regions, 
and five additional sites in three regions for sugar beets.
     In conjunction with previously submitted data an adequate amount 
of geographically representative crop field trial residue data were 
presented which show that the proposed tolerances should not be 
exceeded when quizalofop ethyl is formulated into DUPONT ASSURE II and 
used as directed.
    b. Magnitude of the residue in animals. A ruminant feeding study 
has been submitted and reviewed in PP 5F3252 and PP 1F3951. In summary, 
three groups of three lactating dairy cows plus a control group were 
fed 0.1, 0.5, and 5.0 ppm quizalofop ethyl ester (encapsulated) for 28-
consecutive days. Milk was collected daily and a sub-sample was divided 
into skim milk and cream. Two cows were sacrificed after 28 days with 
samples of fat, skeletal muscle, liver, and kidney being collected and 
analyzed. The remaining cow in each test group was fed a regular diet 
without encapsulated quizalofop ethyl ester for an additional 7 days 
before sacrifice. Whole milk, skim milk, and cream from the control, 
and the 0.1 and 0.5 ppm dose groups showed no quizalofop to <0.02 ppm 
(0.05 ppm in cream). From the 5 ppm dose, quizalofop residues ranged 
from 0.01 to 0.02 ppm in whole, and when these samples were separated 
into cream and skim milk, the quizalofop partitioned into the cream 
with residues plateauing at 0.26 to 0.31 ppm. No quizalofop to <0.02 
ppm was detected in skeletal muscle, and to <0.05 ppm was detected in 
any liver or fat sample from any of the three doses. Quizalofop was 
detected in one kidney sample as 0.05 ppm from the 5 ppm dose.
     From the feed items in this petition, all of the feed items in 
cattle diets can be treated with quizalofop ethyl ester. A theoretical 
beef cattle diet consisting of bean and pea forage, canola meal, pea 
hay, and sugar beet tops which none-the-less maximizes the potential 
quizalofop exposure of 2.1 ppm. A theoretical dairy cattle diet 
consisting of pea and bean forage would none-the-less maximize the 
potential quizalofop exposure at 2.4 ppm. Substitutions of other feed 
items and varying their percentages in the diets would give a lower-
dietary quizalofop burden.
     The results of the quizalofop ethyl ester bovine feeding study 
show that finite residues will actually occur in milk and tissues from 
the feeding of quizalofop ethyl ester treated raw agricultural 
commodities (RACs) or their processed feed items when DUPONT ASSURE II 
is used as directed. The established quizalofop and quizalofop ethyl 
ester tolerance in milk, and in fat, meat, and meat by-products of 
cattle, goats, hogs, horse, and sheep are adequate and need not be 
increased from these additional uses.
     A poultry feeding study has been submitted and reviewed (ibid). In 
summary, three groups of 20 hens (plus one control group) were dosed 
with

[[Page 52259]]

encapsulated quizalofop ethyl ester at 0.1, 0.5, and 5 ppm daily for 
28-consecutive days. Eggs were collected daily, and after 28 days 
1/89/21/13/27/81/163/8 of the hens in each test group were 
sacrificed, and samples of fat, liver, kidney, breast and thigh muscles 
were collected and analyzed. Tissues from each test group were pooled 
prior to analysis. The remaining five hens were fed a regular poultry 
diet without quizalofop ethyl ester for an additional 7 days before 
sacrifice. No quizalofop residues were detected in the liver to <0.05 
ppm, and in breast and thigh muscles to <0.02 ppm for any dose 
administered. From the 5 ppm dose, one kidney sample showed 0.09 ppm 
quizalofop, two fat samples were 0.05 and 0.06 ppm quizalofop, and one 
egg sample was 0.02 ppm quizalofop.
     The results of the quizalofop ethyl ester poultry feeding study 
show that while it is not possible to establish with certainty whether 
finite residues will actually occur in eggs and tissues from the 
feeding of quizalofop ethyl ester treated RACS or their processed feed 
items when DUPONT ASSURE II is used as directed, there is a reasonable 
expectation for such residues to occur. The established tolerance of 
quizalofop and quizalofop ethyl ester in eggs, and in fat, meat, and 
meat by-products of poultry are adequate and need not be changed from 
these additional uses.

B. Toxicological Profile

    1. Acute toxicity. Several acute toxicology studies were conducted 
and the overall results placed technical grade quizalofop ethyl in 
toxicity Category III. These include the following studies in Category 
III: acute oral toxicity (LD50s 1,480 and 1,670 for female 
and male rats, respectively)and eye irritation (mild effects; 
reversible within 4 days). Dermal toxicity (LD50 > 5,000 
milligram/kilogram (mg/kg); rabbit), inhalation toxicity 
LC50 >5.8 (mg/Liter (L)); rat) and dermal irritation were 
classified within Category IV. Technical quizalofop ethyl was not a 
dermal sensitizer.
    2. Genotoxicty. Technical quizalofop ethyl was negative in the 
following genotoxicity tests: Bacterial gene mutation assays with E. 
coli and S. typhimurium; gene mutation assays in Chinese hamster ovary 
(CHO) cells; in vitro DNA damage assays with B. subtillis and in rat 
hepatocytes; and an in vitro chromosomal aberration test in CHO cells.
    3. Reproductive and developmental toxicity. Studies supporting the 
registration include: A developmental toxicity study in rats 
administered dosage levels of 0, 30, 100, and 300 mg/kg/day on days 6 
to 15 of gestation. The maternal toxicity no observed effect level 
(NOEL) was 30 mg/kg/day and a developmental toxicity NOEL was greater 
than 300 mg/kg/day. The maternal NOEL was based on reduced food 
consumption and increased liver weights at 100 and 300 mg/kg/day and 
reduced maternal weight gain at 300 mg/kg/day. There was an equivocal 
effect on maternal weight gain in the 100 mg/kg/day group (body weight 
in this group was lower before the outset of dosing, so unclear if 
subsequent effects were compound related).
     A developmental toxicity study in rabbits administered dosage 
levels of 0, 7, 20, and 60 mg/kg/day on days 7-19 of gestation with no 
developmental effects noted at 60 mg/kg/day. The maternal toxicity NOEL 
was 20 mg/kg/day based on decreases in food consumption at 60/mg/kg/
day.
     A 2-generation reproduction study in rats fed diets containing 0, 
25, 100, or 400 ppm (or approximately 1, 1.25, 5, and 20 mg/kg/day, 
respectively) with a developmental (systemic effects) NOEL of 1.25 mg/
kg/day for F2B weanlings based on increased liver weights and increased 
incidence of eosinophilic changes in the livers at 5.0 mg/kg/day. These 
liver changes were considered to be physiological or adaptive changes 
to compound exposure among weanlings. When access to the mother's feed 
is available, it is a common observation that young rats will begin 
consuming chow prior to complete weaning at 21 days of age. Consumption 
could not be quantified; therefore, the maternal consumption was 
assumed as the NOEL (if normalized on a body weight basis, exposures to 
the weanling rats were likely higher). The parental NOEL of 5.0 mg/kg/
day was based on decreased body weight and premating weight gain in 
males at 20 mg/kg/day, highest dose level (HDT).
    4. Subchronic toxicity. A 90-day study was conducted in rats fed 
diets containing 0, 40, 128, and 1,280 ppm (or approximately 0, 2, 6.4, 
and 64 mg/kg/day, respectively). The NOEL was 2 mg/kg/day. This was 
based on increased liver weights at 6.4 mg/kg.
     A 90-day feeding study in mice was conducted with diets that 
contained 0, 100, 316, or 1,000 ppm (or approximately 0, 15, 47.4, and 
150 mg/kg/day, respectively). The NOEL was <15 mg/kg/day, lowest dose 
level (LDT) based on increased liver weights and reversible 
histopathological effects in the liver at the LDT.
     A 6-month feeding study in dogs was conducted with diets that 
contained 0, 25, 100, or 400 ppm (or approximately 0, 0.625, 2.5, and 
10 mg/kg/day, respectively). The NOEL was 2.5 mg/kg/day based on 
increased blood urea nitrogen at 10 mg/kg/day.
     A 21-day dermal study was conducted in rabbits at doses of 0, 125, 
500, or 2,000 mg/kg/day. The NOEL was 2,000 mg/kg/day HDT.
    5. Chronic toxicity. An 18-month carcinogenicity study was 
conducted in CD-1 mice fed diets containing 0, 2, 10, 80 or 320 ppm (or 
approximately 0, 0.3, 1.5, 12, and 48 mg/kg/day, respectively). There 
were no carcinogenic effects observed under the conditions of the study 
at levels up to and including 12 mg/kg/day. A marginal increase in the 
incidence of hepatocellular tumors was observed at 48 mg/kg/day HDT, 
which exceeded the maximum tolerated dose (MTD). (Please see the 
discussion by the EPA HED Carcinogenicity Peer Review Committee.)
     A 2-year chronic toxicity/carcinogenicity study was conducted in 
rats fed diets containing 0, 25, 100, or 400 ppm (or 0, 0.9, 3.7, and 
15.5 mg/kg/day for males and 0, 1.1, 4.6, and 18.6 mg/kg/day for 
females, respectively). There were no carcinogenic effects observed 
under the conditions of the study at levels up to and including 18.6 
gram (g)/kg/day HDT. The systemic NOEL was 0.9 mg/kg/day based on 
altered red cell parameters and slight/minimal centrilobuler 
enlargement of the liver at 3.7 mg/kg/day.
     A 1-year feeding study was conducted in dogs fed diets containing 
0, 25, 100, or 400 ppm (or approximately 0, 0.625, 2.5, and 10 mg/kg/
day, respectively). The NOEL was 10 mg/kg/day HDT. EPA has classified 
quizalofop ethyl as carcinogenicity Category D (not classifiable as to 
human cancer potential).
    6. Animal metabolism. The metabolism of quizalofop ethyl in animals 
(goat, poultry, and rat) is well understood. 14C-phenyl and 
14C-quinoxaline quizalofop ethyl ester metabolism studies 
have been conducted in each species. There are similarities among these 
species with respect to metabolism. Quizalofop ethyl is rapidly and 
extensively metabolized and rapidly excreted by rats. The principal 
metabolites were the quizalofop-p acid and two dechlorinated 
hydroxylated forms of the acid. Tissue residues were minimal and there 
was no evidence of accumulation of quizalofop ethyl or its metabolites 
in the rat.
     The primary pathway in ruminants is hydrolysis of the ethyl ester 
to form the quizalofop-p methyl ester. In poultry, the primary 
metabolic pathway is also the hydrolysis of the ethyl ester to form the 
quizalofop-p acid, then the methyl

[[Page 52260]]

esterification to form the quizalofop methyl ester becomes a minor 
pathway.
     The nature of the quizalofop ethyl ester residue in livestock is 
adequately understood. The residues of concern are quizalofop ethyl, 
quizalofop methyl, and quizalofop, all expressed as quizalofop ethyl.
    7. Metabolite toxicology. There is no evidence that the metabolites 
of quizalofop ethyl as identified as either the plant or animal 
metabolism studies are of any toxicological significance.
    8. Endocrine disruption No special studies investigating potential 
estrogenic or other endocrine effects of quizalofop p-ethyl have been 
conducted. However, the standard battery of required toxicology studies 
has been completed. These include an evaluation of the potential 
effects on reproduction and development, and an evaluation of the 
pathology of the endocrine organs following repeated or long-term 
exposure to doses that far exceed likely human exposures. Based on 
these studies there is no evidence to suggest that quizalofop p-ethyl 
has an adverse effect on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure. An analysis of chronic dietary risk was 
conducted to determine the total exposure from current and proposed 
final tolerances for quizalofop-P-ethyl. A chronic reference dose 
(CRfD) of 0.009 mg/kg/day was used in the analyses based on a NOEL of 
0.9 mg/kg/day from the chronic rat dietary study and a 100x uncertainty 
factor. Using very conservative criteria, an acute reference dose 
(ARfD) of 0.3 mg/kg/day based on a maternal NOEL of 30 mg/kg/day (and a 
100x uncertainty factor) from rat developmental toxicity study in which 
an effect on maternal body weight may have occurred at the outset of 
dosing. Although, there was a NOEL of 20 mg/kg/day in a rabbit 
developmental toxicity study, this was based only on lower overall food 
consumption in the absence of body weight effects during dosing and may 
not represent acute toxicity since all groups including vehicle-dosed 
controls had lower food consumption at the outset of dosing.
     i. Food. The chronic dietary exposure assessment was conducted 
using the Dietary Exposure Evaluation Model (DEEMTM) Version 
7.76 based on the current published tolerances and the proposed 
tolerances. The estimated exposure was 0.000343 mg/kg body weight/day 
for the U.S. population (total) and 0.000892 mg/kg body weight/day for 
the population subgroup with the highest estimated exposure (children 
age 1-6 years). For the U.S. population subgroup this exposure 
represents approximately 3.8% of the CRfD while for the population with 
the highest estimated exposure, this represents approximately 9.9% of 
the CRfD. Based on the risk estimates arrived at in this analysis, 
chronic dietary risk from the current and proposed uses of DUPONT 
ASSURE II is minimal.
     The acute dietary exposure assessment was conducted using the 
DEEMTM Version 7.76 based on the current published 
tolerances and the proposed tolerances. The estimated exposure was 
0.004189 mg/kg body weight/day (99.9th percentile) for the 
U.S. population (total) and 0.006847 mg/kg body weight/day 
(99.9thpercentile) for the population subgroup with the 
highest estimated exposure (non-nursing infants <1 year old). For the 
U.S. population subgroup this exposure represents approximately 1.4% of 
the ARfD while for the population with the highest estimated exposure, 
this represents approximately 2.28% of the ARfD. Based on the risk 
estimates arrived at in this analysis, acute dietary risk from the 
current and proposed uses of DUPONT ASSURE II is minimal.
    ii. Drinking water. Acute and chronic surface water exposures were 
estimated using the FQPA Index Reservoir Screening Tool (FIRST) and the 
Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/
EXAMS) models. Ground water exposures were estimated using Screening 
Concentration in Ground Water (SCI-GROW).
     The EPA uses drinking water levels of comparisons (DWLOCs) as a 
surrogate measure to capture risk associated with exposure to 
pesticides in drinking water. A DWLOC is the concentration of a 
pesticide in drinking water that would be acceptable as an upper limit 
in light of total aggregate exposure to that pesticide from food, 
water, and residential uses. Since there are no residential uses for 
quizalofop ethyl, the aggregate exposure is due to food and water only. 
A DWLOC will vary depending on the residue level in foods, the toxicity 
endpoint, and with drinking water consumption patterns and body weights 
for specific subpopulations.
     The acute and chronic DWLOC concentrations are likely to be many 
orders of magnitude higher than those estimated by the models listed in 
this unit. Therefore, one can conclude with reasonable certainty that 
residues of quizalofop ethyl in drinking water do not contribute 
significantly to the aggregate acute or chronic human health risk.
    2. Non-dietary exposure. Quizalofop ethyl is not registered for any 
use that could result in non-occupational, non-dietary exposure to the 
general population.

D. Cumulative Effects

     There is no evidence to indicate or suggest that quizalofop p-
ethyl has any toxic effects on mammals that would be cumulative with 
those of any other chemicals.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described in Unit C.1. and based on the most sensitive species chronic 
NOEL of 0.9 mg/kg and a CRfD of 0.009 mg/kg/day, the existing 
tolerances and proposed uses of quizalofop ethyl on beans, peas, and 
sugar beet are estimated to utilize 3.8% of the CRfD for the general 
U.S. population. Using the conservative exposure assumptions described 
in Unit C.1. and based on the most sensitive species acute NOEL of 30 
mg/kg and a ARfD of 0.3 mg/kg/day, the existing tolerances and proposed 
use of quizalofop ethyl on beans, peas, and sugar beet are estimated to 
utilize 1.4% of the ARfD for the general U.S. population.
     These results fall below HED's level of concern (>100% RfD) and 
indicate that there is reasonable certainty that no chronic or acute 
effects would result from exposure to quizalofop p-ethyl with the 
recommended agricultural uses.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of quizalofop ethyl, 
data were considered from developmental toxicity studies in the rat and 
rabbit, and a multi-generation reproduction study in rats. There were 
no developmental effects observed in the absence of maternal toxicity 
in the rat and rabbit developmental studies. Minimal adaptive or 
physiological effects were observed in livers of weanlings in the 2-
generation rat reproduction study described in Unit B.3. However, this 
effect was only observed at a dose that far exceeds any expected human 
exposure. Further, the NOEL of 0.9 mg/kg/day from the 2-year rat study 
with quizalofop ethyl which was used to calculate the RfD (discussed in 
Unit C.1.), is already lower than any of the NOELs defined in the 
developmental and reproductive toxicity studies with quizalofop ethyl.
     As indicated in Unit C.1.i., infants and children have a low 
potential for quizalofop ethyl exposure. The toxicology profile of 
quizalofop ethyl

[[Page 52261]]

demonstrates low mammalian toxicity. Because there was no evidence that 
offspring were uniquely susceptible to the toxic effects of quizalofop 
ethyl, an additional 10-fold uncertainty factor should not be required 
to protect infants and children. Therefore, the RfD of 0.009 mg/kg/day, 
which utilizes a 100-fold safety factor, is appropriate to assure a 
reasonable certainty of no harm to infants and children from aggregate 
exposure to quizalofop ethyl.

F. International Tolerances

    Since there are no Mexican or Codex MRLs tolerances, compatibility 
is not a problem at this time. Compatibility cannot be achieved with 
the Canadian negligible residue type limit at 0.1 ppm at the United 
States use pattern, which had findings of real residues above 0.1 ppm.

[FR Doc. 04-19441 Filed 8-24-04; 8:45 am]
BILLING CODE 6560-50-S