[Federal Register: March 20, 2003 (Volume 68, Number 54)]
[Notices]               
[Page 13703-13708]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20mr03-60]                         

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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0056; FRL-7296-5]

 
Flufenacet; Notice of Filing Pesticide Petitions to Establish 
Tolerances 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 
flufenacet in or on various food commodities.

DATES: Comments, identified by docket ID number OPP-2003-0056, must be 
received on or before April 21, 2003.

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: 
tompkins.jim@epa.gov.

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:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] Pesticide manufacturing (NAICS 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in 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 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-2003-0056. 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 

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.

[[Page 13704]]

Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B. EPA intends to work towards 
providing electronic access to all of the publicly available docket 
materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through hand 
delivery/courier. To ensure proper receipt by EPA, identify the 
appropriate docket ID number in the subject line on the first page of 
your comment. Please ensure that your comments are submitted within the 
specified comment period. Comments received after the close of the 
comment period will be marked ``late.'' EPA is not required to consider 
these late comments. If you wish to submit CBI or information that 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 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-2003-0056. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov, 

Attention: Docket ID Number OPP-2003-0056. 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-2003-0056.
    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-2003-0056. 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

[[Page 13705]]

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: March 10, 2003.
Debra Edwards,
Acting 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 the petitioner and represents the view of the petitioner. 
The petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

Bayer CropScience

PP 6F4631 and OF6095

    EPA has received pesticide petitions (6F4631 and 0F6095) from 
BayerCropScience, P.O. Box 12014, 2 T.W. Alexander Drive, Research 
Triangle Park, NC 27709 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 180.527(a) by establishing permanent tolerance[s] for 
residues of the herbicide flufenacet; N-(4-fluorophenyl)-N-(1-
methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-
yl]oxy]acetamide and metabolites containing the 4-fluoro-N-methylethyl 
benzenamine moiety in or on the raw agricultural commodities: corn, 
field, forage at 0.4 parts per million (ppm); corn, field, grain at 
0.05 ppm; corn, field, stover at 0.4 ppm; soybean, seed at 0.1 ppm (PP 
6F4631); cattle, fat at 0.05 ppm; cattle, kidney at 0.5 ppm; cattle, 
meat at 0.05 ppm; cattle, meat byproducts at 0.1 ppm; goat, fat at 0.05 
ppm; goat, kidney at 0.5 ppm; goat, meat at 0.05 ppm; goat, meat 
byproducts at 0.1 ppm; hog, fat at 0.05 ppm; hog, kidney at 0.5 ppm; 
hog, meat at 0.05 ppm; hog, meat byproducts at 0.1 ppm; horse, fat at 
0.05 ppm; horse, kidney at 0.5 ppm; horse, meat at 0.05 ppm; horse, 
meat byproducts at 0.1 ppm; sheep, fat at 0.05 ppm; sheep, kidney at 
0.5 ppm; sheep, meat at 0.05 ppm; sheep, meat byproducts at 0.1 ppm; 
wheat, forage at 10.0 ppm; wheat, grain at 1.0 ppm; wheat, hay at 2.0 
ppm; wheat, straw at 0.50 ppm (PP 0F6095); and 40 CFR 180.527(d) by 
establishing permanent tolerances for indirect or inadvertent residues 
of the herbicide flufenacet; N-(4-fluorophenyl)-N-(1-methylethyl)-2-
[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide and 
metabolites containing the 4-fluoro-N-methylethyl benzenamine moiety in 
or on the following raw agricultural commodities from the application 
of this herbicide to the raw agricultural commodities listed in 40 CFR 
180.527(a): alfalfa, forage at 0.1 ppm; alfalfa, hay at 0.1 ppm; 
alfalfa, seed at 0.1 ppm; clover, forage at 0.1 ppm; clover, hay at 0.1 
ppm; grain, cereal, group 15, except rice at 0.4 ppm; grain, cereal, 
forage, fodder and straw, group 16, except rice, forage at 10.0 ppm; 
grain, cereal, forage, fodder and straw, group 16, except rice, stover 
at 3.0 ppm; grain, cereal, forage, fodder, and straw, group 16, except 
rice, straw at 1.0 ppm; grass, forage, fodder, and hay, group 17 at 0.1 
ppm (PP 6F4631).

A. Residue Chemistry

    1. Plant metabolism. The nature of the residue in field corn, 
soybean, rotational crops and livestock is adequately understood. The 
residues of concern for the tolerance expression are flufenacet parent 
and its metabolites containing the 4-fluoro-N-methylethyl benzenamine 
moiety. Based on the results of animal metabolism studies, it is 
unlikely that secondary residues would occur in animal commodities from 
the use of flufenacet on field corn and soybean.
    2. Analytical method. An adequate analytical method, 
gaschromatography/mass spectrometry with selected ion monitoring, is 
available for enforcement purposes. Because of the long lead time from 
establishing these tolerances to publication of the enforcement 
methodology in the Pesticide Analytical Manual, Vol. II, the analytical 
methodology is being made available in the interim to anyone interested 
in pesticide enforcement when requested from: Calvin Furlow, Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460. Office 
location and telephone number: Room 119E, CM 2, 1921 Jefferson 
Davis Highway, Arlington, VA 22202, (703) 305-5937).
    3. Magnitude of residues. Field residue trials were conducted 
across the major regions of corn and soybean production in the United 
States. In both cases, the treatment regime was selected to represent 
the use patterns that are most likely to result in the highest residue 
and used a 60% dry flowable formulation of the active ingredient. In 
all cases, the test plots received a single application of the product 
at a rate of 0.9 lbs. of active ingredient per acre.
    For corn, flufenacet was applied at preplant soil incorporated, 
preemergence broadcast, and early postemergence application timings. 
The highest average field trial residues in corn raw agricultural 
commodities were 0.36 ppm in forage, 0.16 ppm in fodder, and less than 
0.05 ppm in grain. No significant concentration of these residues 
occurred when the corn grain was processed by either wet or dry milling 
procedures.
    For soybean, flufenacet was applied as a preplant broadcast 
treatment that was incorporated to a depth of approximately 2 inches or 
as a preemergent broadcast treatment made within 1 day of planting the 
soybean crop. The maximum residues detected were 0.10 ppm in seed, 1.20 
ppm in green forage, and 9.75 ppm in dry hay.

B. Toxicological Profile

    1. Acute toxicity. i. Technical grade flufenacet has a low to 
moderate order of toxicity in rats by the oral route of exposure. The 
acute oral LD50 was 1,617 milligrams/kilogram (mg/kg) for 
males and 589 mg/kg for females.
    ii. A dermal toxicity study on technical grade flufenacet revealed 
low acute toxicity to rats. The dermal LD50 for both sexes 
was >2,000 mg/kg, the highest dose tested.
    iii. An acute inhalation study on technical grade flufenacet showed 
low toxicity in rats with a 4-hour liquid aerosol LC50 for 
males and females of >3,740 mg/m3 air, the highest 
concentration tested.
    iv. An eye irritation study on technical grade flufenacet in 
rabbits showed minimal irritation to the

[[Page 13706]]

conjunctiva completely reversible within 7 days.
    v. A dermal irritation study on technical grade flufenacet in 
rabbits did not produced any irritation.
    vi. Skin sensitization studies on technical grade flufenacet in 
guinea pigs have produced equivocal results. A skin sensitization 
potential was exhibited under the conditions of a maximization test, 
whereby, there was no skin sensitization potential when tested by the 
Buehler Topical Closed Patch Technique.
    2. Genotoxicty. Flufenacet was negative for mutagenic/genotoxic 
effects in a gene mutation/in vitro assay in bacteria, a gene mutation/
in vitro assay in Chinese hamster lung fibroblasts cells, a 
cytogenetics/in vitro assay in Chinese hamster ovary cells, a 
cytogenetics/in vivo mouse micronucleus assay, and an in vitro 
unscheduled DNA synthesis assay in primary rat hepatocytes.
    3. Reproductive and developmental toxicity. i. A two-generation rat 
reproduction study with a parental systemic no observed adverse effect 
level (NOAEL) of 20 ppm (1.4 mg/kg/day in males and 1.5 mg/kg/day in 
females) and a reproductive NOAEL of 20 ppm (1.3 mg/kg/day) and a 
parental systemic lowest observed adverse effect level (LOAEL) of 100 
ppm (7.4 mg/kg/day in males and 8.2 mg/kg/day in females) based on 
increased liver weight in F1 females and hepatocytomegaly in 
F1 males and a reproductive LOAEL of 100 ppm (6.9 mg/kg/day) 
based on increased pup death in early lactation (including cannibalism) 
for F1 litters and the same effects in both F1 
and F2 pups at the high dose level of 500 ppm (37.2 mg/kg/
day in F1 males and 41.5 mg/kg/day in F1 females, 
respectively).
    ii. A rat developmental study with a maternal NOAEL of 25 mg/kg/day 
and with a maternal LOAEL of 125 mg/kg/day based on decreased body 
weight gain initially and a developmental NOEL of 25 mg/kg/day and a 
developmental LOAEL of 125 mg/kg/day based on decreased fetal body 
weight, delayed development (mainly delays in ossification in the 
skull, vertebrae, sternebrae, and appendages), and an increase in the 
incidence of extra ribs.
    iii. A rabbit developmental study with a maternal NOAEL of 5 mg/kg/
day and a maternal LOAEL of 25 mg/kg/day based on histopathological 
finds in the liver and a developmental NOAEL of 25 mg/kg/day and a 
developmental LOAEL of 125 mg/kg/day based on increased skeletal 
variations.
    4. Subchronic toxicity. i. A 84-day rat feeding study with a NOAEL 
less than 100 ppm (6.0 mg/kg/day) for males and a NOAEL of 100 ppm (7.2 
mg/kg/day) for females and with a LOAEL of 100 ppm (6.8 mg/kg/day) for 
males based on suppression of thyroxine (T4) level and a LOAEL of 400 
ppm (28.8 mg/kg/day) for females based on hematology and clinical 
chemistry findings.
    ii. A 13-week mouse feeding study with a NOAEL of 100 ppm (18.2 mg/
kg/day for males and 24.5 mg/kg/day for females) and a LOAEL of 400 ppm 
(64.2 mg/kg/day for males and 91.3 mg/kg/day for females) based on 
histopathology of the liver, spleen and thyroid.
    iii. A 13-week dog dietary study with a NOAEL of 50 ppm (1.70 mg/
kg/day for males and 1.67 mg/kg/day for females) and a LOAEL of 200 ppm 
(6.90 mg/kg/day for males and 7.20 mg/kg/day for females) based on 
evidence that the bio-transformation capacity of the liver has been 
exceeded, (as indicated by an increase in LDH, liver weight, ALK and 
hepatomegaly), globulin and spleen pigment in females, decreased T4 and 
ALT values in both sexes, decreased albumin in males, and decreased 
serum glucose in females.
    iv. A 21-day rabbit dermal study with the dermal irritation NOAEL 
of 1,000 mg/kg/day for males and females and a systemic NOAEL of 20 mg/
kg/day for males and 150 mg/kg/day for females and a systemic LOAEL of 
150 mg/kg/day for males and 1,000 mg/kg/day for females based on 
clinical chemistry data (decreased T4 and FT4 levels in both sexes) and 
centrilobular hepatocytomegaly in females.
    5.Chronic toxicity. i. A 1-year dog chronic feeding study with a 
NOAEL was 40 ppm (1.29 mg/kg/day in males and 1.14 mg/kg/day in 
females) and a LOAEL of 800 ppm (27.75 mg/kg/day in males and 26.82 mg/
kg/day in females) based on increased alkaline phosphatase, kidney, and 
liver weight in both sexes, increased cholesterol in males, decreased 
T2, T4 and ALT values in both sexes, and increased incidences of 
microscopic lesions in the brain, eye, kidney, spinal cord, sciatic 
nerve and liver.
    ii. A rat chronic feeding/carcinogenicity study with a NOAEL less 
than 25 ppm (1.2 mg/kg/day in males and 1.5 mg/kg/day in females) and a 
LOAEL of 25 ppm (1.2 mg/kg/day in males and 1.5 mg/kg/day in females) 
based on methemoglobinemia and multi-organ effects in blood, kidney, 
spleen, heart, and uterus. Under experimental conditions the treatment 
did not alter the spontaneous tumor profile.
    iii. In a mouse carcinogenicity study the NOAEL was less than 50 
ppm (7.4 mg/kg/day) for males and the NOAEL was 50 ppm (9.4 mg/kg/day) 
for females and the LOAEL was 50 ppm (7.4 mg/kg/day) for males and the 
LOAEL was 200 ppm (38.4 mg/kg/day) for females based on cataract 
incidence and severity. There was no evidence of carcinogenicity for 
flufenacet in this study.
    6. Animal metabolism. A rat metabolism study showed thatradio-
labeled flufenacet was rapidly absorbed and metabolized by both sexes. 
Urine was the major route of excretion at all dose levels and smaller 
amounts were excreted via the feces.
    7. Metabolite toxicology. A 55-day dog study withsubcutaneous 
administration of thiadone (flufenacet metabolite) supports the 
hypothesis that limitations in glutathione interdependent pathways and 
antioxidant stress result in metabolic lesions in the brain and heart 
following flufenacet exposure.
    8. Endocrine disruption. EPA is required to develop ascreening 
program to determine whether certain substances (including all 
pesticides and inerts) may have an effect in humans that is similar to 
an effect produced by a naturally occurring estrogen, or such other 
effect. The Agency is currently working with interested stakeholders, 
including other government agencies, public interest groups, industry 
and research scientists in developing a screening and testing program 
and a priority setting scheme to implement this program. Congress has 
allowed 3 years from the passage of FQPA (August 3, 1999) to implement 
this program. At that time, EPA may require further testing of this 
active ingredient and end use products for endocrine disrupter effects. 
Based on the toxicological findings for flufenacet relating to 
endocrine disruption effects, flufenacet should be considered as a 
candidate for evaluation as an endocrine disrupter when the criteria 
are established.
    9. Other studies. i. An acute rat neurotoxicity study with a NOAEL 
less than 75 mg/kg/day and a LOAEL of 75 mg/kg/day based on decreased 
motor activity in males.
    ii. A rat subchronic neurotoxicity study with a NOAEL of 120 ppm 
(7.3 mg/kg/day in males and 8.4 mg/kg/day in females) and a LOAEL of 
600 (38.1 mg/kg/day in males and 42.6 mg/kg/day in females) based on 
microscopic lesions in the cerebellum/medulla and spinal cords.
    iii. A rat developmental neurotoxicity dietary study established an 
overall NOAEL for both dams and offspring of 17.5 ppm. A LOAEL of 80.8 
ppm was established based on body weight and

[[Page 13707]]

feed consumption declines common to both dams and offspring as well as 
developmental delays which were noted in the offspring (eye opening, 
preputial separation). No evidence of specific neurobehavioral effects 
in the offspring were observed at dietaryconcentrations of up to 404 
ppm.

C. Aggregate Exposure

    1. Dietary exposure. Flufenacet is an herbicide withcurrently 
registered uses on corn and soybean. Section 18 emergency exemptions 
for use on wheat have been approved in several states. Also, time 
limited tolerances exist for inadvertent or indirect residues on 
alfalfa, clover, and crop groups 15, 16 and 17. Tolerances are proposed 
for use on Crop Group 1C, tuberous and corm vegetables, which includes 
potatoes and sweet potatoes. There are no residential uses for 
flufenacet, therefore aggregate exposure would consist of any potential 
exposure to flufenacet residues in the registered and proposed crops 
and in drinking water.
    i. Food. Acute and Chronic dietary exposure assessments were 
conducted using the Dietary Exposure Evaluation Model (DEEM[reg], 
Version 7.76) from Exponent, Inc. and the 1994-1996, 1998 CSFII 
consumption database. Dietary exposure values were compared to the 
acute RfD of 0.083 milligrams/kilogram of body weight per day (mg/kg 
bw/day) based on a LOEL from an acute neurotoxicity study in rats and a 
900-fold uncertainty factor. The chronic RfD of 0.004 mg/kg bw/day is 
based on a LOEL from a combined chronic toxicity/carcinogenicity study 
in the rat with a 300-fold uncertainty factor.
    The refined acute and chronic dietary risk assessments were 
performed using anticipated residues for all registered and proposed 
crops and crop groups. Adjustments were made to account for percent of 
crop treated and processing factors where available. The Tier 2 acute 
analysis resulted in the U.S. population using 0.00437 mg/kg bw/day or 
5.2% of the acute RfD. The highest exposed subpopulation was non-
nursing infants at 0.00893 mg/kg bw/day utilized or 10.7% of the acute 
RfD.
    For the Tier 3 chronic analysis the U.S. population utilized 
0.000087 mg/kg bw/day or 2.2% of the chronic RfD. The highest exposed 
subpopulation was children 1-6 at 0.000179 mg/kg bw/day or 4.5% of the 
chronic RfD.
    ii. Drinking water. The EPA has calculated drinking waterlevel of 
comparison (DWLOCs) for acute exposure to flufenacet in drinking water 
as 2.87 ppm for the U.S. population and 813 ppb for children (1-6 years 
old). The Agency's screening concentration in ground water (SCI-Grow) 
model estimates peak levels of flufenacet and its metabolite thiadone 
in groundwater to be 15.3 ppb. EPA's Pesticide Root Zone Model/Exposure 
Analysis Modeling System (PRZM/EXAMS) estimates peak levels of 
flufenacet and its metabolite thiadone in surface water to be 17 ppb. 
EPA's acute drinking water levels of comparison are well above the 
estimated exposures for flufenacet in water for the U.S. population and 
the subgroup with highest estimated exposure.
    The EPA has calculated the drinking water level of comparison for 
chronic exposure to flufenacet in drinking water as 136 ppb for the 
U.S. population assuming that an adult weighs 70 kg and consumes a 
maximum of 2 liters of water per day. For children (1-6 years old), the 
DWLOC was 37.7 ppb assuming that a child weighs 10 kg and consumes a 
maximum of 1 liter of water per day. The drinking water estimated 
concentration (DWECs) for groundwater (parent flufenacet and degradate 
thiadone) calculated from modeling data is 0.03 ppb for chronic 
concentrations which does not exceed the DWLOC of 37.7 ppb for children 
(1-6 years old). The DWEC for surface water based on the computer 
models PRZM 2.3 and EXAMS 2.97.5 was calculated to be 14.2 ppb for 
chronic concentration (parent flufenacet and degradate thiadone) which 
does not exceed the DWLOC of 37.7 ppb for children (1-6 years old). The 
EPA has concluded that there is a reasonable certainty that no harm 
will result from aggregate exposure to flufenacet residues.
    2. Non-dietary exposure. There are no non-food uses of flufenacet 
currently registered under the Federal Insecticide, Fungicide and 
Rodenticide Act, as amended. No non-dietary exposures are expected for 
the general population.

D. Cumulative Effects

    Flufenacet is structurally a thiadiazole. EPA is not aware of any 
other pesticides with this structure. For flufenacet, EPA has not yet 
conducted a detailed review of common mechanisms to determine whether 
it is appropriate, or how to include this chemical in a cumulative risk 
assessment. After EPA develops a methodology to address common 
mechanism of toxicity issues to risk assessments, the Agency will 
develop a process (either as part of the periodic review of pesticides 
or otherwise) to reexamine these tolerance decisions. Unlike other 
pesticides for which EPA has followed a cumulative risk approach based 
on a common mechanism of toxicity, flufenacet does not appear to 
produce a toxic metabolite produced by other substances. For the 
purposes of these tolerance actions; therefore, EPA has not assumed 
that flufenacet has a common mechanism of toxicity with other 
substances.

E. Safety Determination

    1. U.S. population. Using the assumptions and data described above, 
it is concluded that chronic dietary exposure to all registered and 
proposed uses of flufenacet will utilize at most 2.2% of the chronic 
RfD for the U.S. population. The acute dietary exposure assessment 
results in the U.S. population utilizing 5.2% of the acute RfD. EPA 
generally has no concern for exposures below 100% of the acute or 
chronic reference dose. Drinking water levels of comparison based on 
the dietary exposure are greater than the highly conservative drinking 
water estimated concentrations as shown above. Therefore, there is a 
reasonable certainty that no harm will occur to the U.S. population 
from aggregate exposure (food and drinking water) to residues of 
flufenacet.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of flufenacet, EPA 
considered data from developmental toxicity studies in the rat and 
rabbit and a two-generation reproduction study in the rat. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from pesticide exposure during 
prenatal development to one or both parents. Reproduction studies 
provide information relating to effects from exposure to the pesticide 
on the reproductive capability of mating animals and data on systemic 
toxicity. FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for pre- and post-natal toxicity and the 
completeness of the data base unless EPA determines that a different 
margin of safety will be safe for infants and children. Although there 
is no indication of increased sensitivity to young rats or rabbits 
following pre- and/or post-natal exposure to flufenacet in the standard 
developmental and reproductive toxicity studies, an additional 
developmental neurotoxicity study, which is not normally required, is 
needed to access the susceptibility of the offspring in function/
neurological development. Therefore, EPA has required that a 
developmental neurotoxicity study be conducted with flufenacet and a 
threefold safety factor for children and infants will be used in the 
aggregate dietary acute and chronic

[[Page 13708]]

risk assessment. Although there is no indication of additional 
sensitivity to young rats or rabbits following pre- and/or post-natal 
exposure to flufenacet in the developmental and reproductive toxicity 
studies; the Agency concluded that the FQPA safety factor should not be 
removed but instead reduced because:
    i. There was no assessment of susceptibility of the offspring in 
functional/neurological developmental and reproductive studies.
    ii. There is evidence of neurotoxicity in mice, rats, and dogs.
    iii. There is concern for thyroid hormone disruption.
    Using the assumptions and data described in the aggregate exposure 
section and the appropriate safety factors as discussed above it is 
concluded that the most sensitive subpopulations of infants and 
children have a reasonable certainty of no harm. For the chronic 
assessment, the most sensitive subpopulation, children 1-6, uses 4.5% 
of the chronic RfD. The acute assessment shows the most sensitive 
subpopulation to be non-nursing infants at 10.7% of the acute RfD. The 
calculated drinking water levels of comparison (DWLOCs) for children of 
765 ppb (acute) and 38 ppb (chronic) are well above the conservative 
drinking water estimated concentrations. Therefore, there is a 
reasonable certainty that no harm will occur to infants and children 
from aggregate exposure to potential residues of flufenacet in food and 
drinking water.

F. International Tolerances

    Maximum residue levels are established or proposed for countries of 
the European Communities in the following commodities: Cereals at 0.5 
ppm; corn at 0.5 ppm; potato at 0.1 ppm; sunflower at 0.05 ppm; soybean 
at 0.05 ppm; animal meat at 0.05 ppm; animal edible offal's at 0.05 
ppm; animal fat at 0.05 ppm; milk at 0.01 ppm; and eggs at 0.05 ppm.

[FR Doc. 03-6711 Filed 3-19-03; 8:45 am]

BILLING CODE 6560-50-S