[Federal Register Volume 70, Number 143 (Wednesday, July 27, 2005)]
[Notices]
[Pages 43412-43417]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-14736]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2005-0139; FRL-7727-2]


Flucarbazone-sodium; 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-
2005-0139, must be received on or before August 26, 2005.

ADDRESSES: Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Jim 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 are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket ID number OPP-2005-0139. 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,

[[Page 43413]]

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 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-2005-0139. 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-2005-0139. 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-2005-0139.
    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-2005-0139. 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

[[Page 43414]]

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: July 18, 2005.
Donald R. Stubbs,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by FFDCA section 408(d)(3). The summary of the petition was 
prepared by the petitioner and represents the view of the petitioner. 
The petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

Arvesta Corporation

PP 5F6949

    EPA has received a pesticide petition (PP 5F6949) from Arvesta 
Corporation, 100 First Street, Suite 1700, San Francisco, CA 94105, 
proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), 
to amend 40 CFR part 180 by establishing a tolerance for residues of 
flucarbazone-sodium: 4,5-dihydro-3-methoxy-4-methyl-5-oxo-N-[[2-
(trifluoromethoxy)phenyl]sulfonyl]-1H-1,2,4-triazole 1-carboxamide, 
sodium salt; and its N-desmethyl metabolite in or on the raw 
agricultural commodities (RACs):

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
Wheat, forage                               0.30
-------------------------------------------
Wheat, grain                                0.01
-------------------------------------------
Wheat, hay                                  0.10
-------------------------------------------
Wheat, straw                                0.05
------------------------------------------------------------------------

    And combined residues of flucarbazone-sodium and its metabolites 
converted to 2-(trifluoromethoxy)benzene sulfonamide and calculated as 
flucarbazone-sodium in or on the raw agricultural commodities:

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
Milk                                        0.005
-------------------------------------------
Meat and meat byproducts except liver       0.01
 (cattle, goats, sheep, horses, hogs)
-------------------------------------------
Liver (cattle, goats, sheep, horses, hogs)  1.50
------------------------------------------------------------------------

    EPA has determined that the petition contains data or information 
regarding the elements set forth in section 408(d)(2) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data supports granting of the 
petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of flucarbazone-sodium in wheat 
was rapid and extensive. Little or no parent flucarbazone-sodium was 
found in the RACs. A primary metabolic pathway in wheat involved the N-
demethylation of flucarbazone-sodium to give N-desmethyl flucarbazone-
sodium. N-desmethyl flucarbazone-sodium was found in all of the wheat 
RACs. The N-desmethyl flucarbazone-sodium was then either hydrolyzed or 
conjugated with glucose. Another primary metabolic pathway was 
hydrolysis of flucarbazone-sodium yielding sulfonic acid and 
sulfonamide which were isolated, and N,O-dimethyl triazolinone which 
was not isolated. Other metabolites were then subsequently formed by 
oxidative reactions, hydrolytic reactions, and conjugation.
    2. Analytical method--i. Plants. The proposed tolerance expression 
is parent flucarbazone-sodium and N-desmethyl flucarbazone-sodium. An 
analytical method was developed to measure these two analytes in plant 
matrices. This method was validated in wheat tissues. The flucarbazone-
sodium and N-desmethyl flucarbazone-sodium residues are extracted from 
the wheat samples with 0.05 M NH4OH by accelerated solvent 
extraction (ASE). The extracts are purified by a combination of C-18 
solid phase extraction (SPE) and ethylene diamine-N-propyl (PSA) spe. 
The resultant analytes are detected by liquid chromatography/tandem 
mass spectroscopy (lc/ms/ms) and quantified against known amounts of 
deuterated internal standards. The method limit of quantitation (LOQ) 
is 0.01 milligram/kilogram (mg/kg) of either analyte in all wheat 
matrices. The method limit of detection (LOD) is 0.005 mg/kg of either 
analyte in all wheat matrices.

[[Page 43415]]

    ii. Animals. An analytical method was developed to measure the 
residues of flucarbazone-sodium in animal tissues and milk. Since the 
flucarbazone-sodium-related residues were present in ruminant tissues 
as a mixture of bound, conjugated, and unconjugated residues, a method 
was developed that simultaneously extracted and hydrolyzed the majority 
of the flucarbazone-sodium-related residues to flucarbazone-sodium 
sulfonamide. The flucarbazone-sodium residues are simultaneously 
hydrolyzed to flucarbazone-sodium sulfonamide and extracted from the 
animal tissues and milk by heating with 8% trifluoroacetic acid (TFA) 
in water. The analysis of fat was complicated by the large quantities 
of lipids that were released during hydrolysis and extraction. 
Therefore, the flucarbazone-sodium residues are extracted into 
acetonitrile/water (9:1) before they are hydrolyzed to flucarbazone-
sodium sulfonamide. After conversion to flucarbazone-sodium 
sulfonamide, the residues are purified and partitioned. The residues 
are detected by lc/ms/ms and quantified against known amounts of 
deuterated internal standards. The LOQ in the tissues and milk is 0.020 
and 0.005 mg/kg, respectively. The estimated LOD (3x highest background 
response) in the liver, muscle, and milk is 0.014, 0.002, and 0.004 mg/
kg, respectively. The recoveries of flucarbazone-sodium were determined 
in all tissues and milk after fortification with flucarbazone-sodium. 
The average recoveries of flucarbazone-sodium from liver fortified at 
0.020 and 0.100 mg/kg were 104 and 100%, respectively. The average 
recoveries of flucarbazone-sodium from muscle fortified at 0.020 and 
0.100 mg/kg were 97 and 102%, respectively. In milk, the average 
recoveries of flucarbazone-sodium at fortifications of 0.005, 0.010, 
and 0.050 mg/kg were 111 (after correction for background in the 
control samples, the average recovery was 92%), 97 and 91%, 
respectively. An independent laboratory validation of the analytical 
method was performed. The method was successfully validated indicating 
that the method could be satisfactorily run by following the written 
procedure.
    3. Magnitude of residues. Field trials were conducted with wheat at 
36 locations to evaluate the quantity of flucarbazone-sodium residues 
in wheat forage, hay, straw, and grain following treatment with 
flucarbazone-sodium 70WG at a rate of 30 grams active ingredient/
hectacre (g ai/ha). The highest average field trial (HAFT) residue 
detected in forage, hay, and straw were 0.27, 0.08, and 0.04 mg/kg, 
respectively. Residues of flucarbazone-sodium were <0.01 mg/kg in wheat 
grain.

B. Toxicological Profile

    1. Acute toxicity--i. Flucarbazone-sodium is not toxic to fasted 
rats following a single oral administration. The oral lethal dose 
(LD50) is >5,000 mg/kg body weight (bwt) for males and 
females.
    ii. Flucarbazone-sodium is not toxic to rats following a single 
dermal application. The dermal LD50 is >5,000 milligrams/
kilogram/body weight (mg/kg/bwt) for males and females.
    iii. An acute inhalation study with rats showed low toxicity with a 
4-hour dust aerosol lethal concentration (LC50) >5,130 mg/
m3 air for males and females.
    iv. An eye irritation study in rabbits showed only very slight, 
reversible irritation.
    v. A dermal irritation study in rabbits showed flucarbazone-sodium 
is not irritating to skin.
    vi. Flucarbazone-sodium has no skin sensitizing potential under the 
conditions of the maximization test in guinea pigs.
    2. Genotoxicity. The genotoxic action of flucarbazone-sodium was 
studied in bacteria and mammalian cells with the aid of various in 
vitro test systems (Salmonella microsome test, hypoxanthine guanine 
phophoribosyl transferase (HGPRT) test with Chinese hamster V79 cells, 
cytogenetic study with Chinese hamster V79 cells, and unscheduled DNA 
synthesis test) and in one in vivo test (micronucleus test). None of 
the tests revealed any evidence of a mutagenic or genotoxic potential 
of flucarbazone-sodium. The compound did not induce point mutation, DNA 
damage, or chromosome aberration.
    3. Reproductive and developmental toxicity. In a 2-generation 
reproduction study, Wistar rats were administered dietary levels of 
flucarbazone-sodium at levels of 0, 50, 4,000, and 20,000/12,000 parts 
per million (ppm) (dose reduction week 6). The no observed adverse 
effect levels (NOAELs) for reproductive parameters was established at 
4,000 ppm, based on slight reduction in pup weight development at 
12,000 ppm. The NOAELs established for parental males and females were 
4,000 and 50 ppm, respectively.
    i. A developmental toxicity study was conducted with Sprague-Dawley 
rats via oral gavage of flucarbazone-sodium at levels of 0, 100, 300, 
and 1,000 milligrams/kilogram body weight/day (mg/kg bwt/day) on days 6 
through 19 of gestation. There were no signs of maternal toxicity, 
embryotoxicity, fetotoxicity, or teratogenicity at the level of 1,000 
mg/kg bwt/day. Therefore, the maternal and developmental NOAELs for 
rats were established at >1,000 mg/kg bwt/day, the limit dose for this 
study type.
    ii. Himalayan rabbits were administered flucarbazone-sodium at 
levels of 0, 100, 300, 500, or 1,000 mg/kg/bwt by oral gavage days 6 
through 28 post coitum in a test for developmental toxicity. A maternal 
NOAEL of 100 mg/kg bwt/day was established based on clinical findings, 
body weight loss, decreased feed consumption, gastrointestinal changes, 
increased liver weights, and fatty liver changes at 300 mg/kg bwt/day. 
The gestation rate NOAEL of 100 mg/kg bwt/day was based on one abortion 
(assessed as secondary due to maternal toxicity) at 300 mg/kg bwt/day. 
The NOAEL for fetal parameters of 300 mg/kg bwt/day was based on 
decreased fetal weights and delayed ossification at 500 mg/kg bwt/day. 
No teratogenic potential of flucarbazone-sodium was evident in rabbits.
    4. Subchronic toxicity--i. A 28-day dermal rabbit study established 
a systemic NOAEL of >1,000 mg/kg bwt/day (the dermal limit dose) for 
males and females. The local dermal effects, skin thickening, seen at 
1,000 mg/kg were regarded as a result of mechanical friction and of no 
toxicological relevance.
    ii. A 90-day rat feeding study defined a NOAEL at 250 ppm (17.6 mg/
kg bwt/day) for males and 1,000 ppm (101.7 mg/kg bwt/day) for females 
based on a decreased spleen weight in males at 1,000 ppm and on 
immunologic changes at 4,000 ppm in females.
    iii. A 90-day feeding study with male and female B6C3F1 mice 
established a NOAEL of 7,000 ppm (equivalent to >2,083, and 3,051 mg/kg 
bwt/day for males and females, respectively). The dose of 7,000 ppm was 
the HDT.
    iv. A 90-day dog feeding study at levels of 0, 1,000, 5,000, and 
50,000 ppm established a NOAEL of 1,000 ppm (equivalent to 33.8 mg/kg 
bwt/day in males and 35.2 mg/kg bwt/day in females) based on decreased 
thyroxine levels and increased thyroxine-binding capacity, macroscopic 
and microscopic effects on the gastric mucosa and an eosinophilic 
hepatocellular cytoplasm occurring at 5,000 ppm and above. The liver 
enzyme induction at 1,000 ppm was assessed as a slight adaptive 
response in the detoxification process of flucarbazone-sodium but not 
as an adverse effect, due to the absence of clinical chemical changes 
that would indicate liver damage and due to the

[[Page 43416]]

absence of any histopathologic liver changes at this dietary level.
    v. A 28-day (6 hours/day; 5 days/week) subacute inhalation toxicity 
study was conducted with male and female Wistar rats exposed to mean 
actual concentrations of 5.2, 30.0, 180.1 and 513.3 mg/m3 
air. A NOAEL of 5.2 mg/m3 air was established based on 
histopathological changes observed at 30 mg/m3 air and 
above.
    5. Chronic toxicity--i. A 2-year chronic toxicity/oncogenicity 
study was conducted with male and female Wistar rats at dietary levels 
of 0, 2.5, 7.5, 125, and 1,000 mg/kg bwt. A NOAEL of 125 mg/kg was 
established based on increased food consumption (both sexes) and lower 
body weights (females) at 1,000 mg/kg. No carcinogenic potential was 
indicated.
    ii. B6C3F1 mice were administered flucarbazone-sodium via the diet 
at levels of 0, 50, 1,000, and 7,000 ppm in a 2-year carcinogenicity 
study. The NOAEL was established in males and females at 1,000 ppm 
(equivalent to 275 and 459 mg/kg bwt/day, respectively) based on 
reduced body weight gain in both sexes and on increased feed 
consumption in males at the 7,000 ppm level. No carcinogenic potential 
was indicated.
    iii. A 1-year feeding study in dogs at levels of 0, 200, 1,000, and 
5,000 ppm established a NOAEL of 1,000 ppm for males (equal to 35.9 mg/
kg bwt/day) based on decreased body weight development, increased ALAT- 
and ASAT-levels and slightly increased N-demethylase levels. The NOAEL 
of 1,000 ppm for females (equal to 37.1 mg/kg bwt/day) was based on 
body weight gain depression, increased N-demethylase levels, decreased 
T4 levels, and marginally increased liver weight.
    6. Animal metabolism. Flucarbazone-sodium was metabolized via two 
pathways. The major pathway involved the hydrolysis of the urea linkage 
forming sulfonamide and N,O-dimethyltriazolinone. The sulfonamide was 
shown to be the major metabolite in the blood, fat, liver, and muscle 
at 4 to 6 hours following oral administration of phenyl-UL-14C 
flucarbazone-sodium. The sulfonamide was conjugated with glucuronic 
acid or acetate sulfonamide N-glucuronide or N-acetyl sulfonamide or 
hydroxylated and then conjugated with glucuronic acid to form 
hydroxysulfonamide-O-glucuronide prior to elimination in the urine. A 
minor pathway involved N-demethylation of flucarbazone-sodium to form 
N-desmethyl flucarbazone-sodium followed by hydrolysis to form the 
sulfonamide and O-methyltriazolinone. Demethylation of 
N,Odimethyltriazolinone led to the formation of N-methyltriazolinone, 
O-methyltriazolinone, and ultimately, urazole; methyl urethane was 
probably formed from the cleavage of O-methyltriazolinone.
    7. Metabolite toxicology--i. The animal and plant metabolite 
flucarbazone-sodium sulfonamide (trifluoromethoxysulfonamide) has a low 
acute oral toxicity (LD50 >2,000 mg/kg/bwt) in fasted rats.
    ii. The plant metabolite flucarbazone-sodium sulfonamide lactate 
conjugate has no acute oral toxicity (NOAEL: 5,000 mg/kg/bwt) in fasted 
rats.
    iii. The plant metabolite flucarbazone-sodium sulfonamide alanine 
has no acute oral toxicity (NOAEL: 5,000 mg/kg/bwt) in fasted rats.
    iv. The soil metabolite O-desmethyl flucarbazone-sodium has an 
acute oral LD50 value in fasted male and female rats of 
>2,500 - <5,000 mg/kg bwt.
    v. The plant, animal, and soil metabolite, MKH 10868 (flucarbazone-
sodium sulfonic acid Na-salt), has no acute oral toxicity 
(LD50 >5,000 mg/kg bwt) in fasted male and female rats.
    vi. MKH 10868 was considered non-mutagenic with and without S9 mix 
in the plate incorporation as well as in the preincubation modification 
of the Salmonella/microsome test.
    8. Endocrine disruption. There is no evidence to suggest that 
flucarbazone-sodium has an effect on the endocrine system. Studies in 
this data base include evaluation of the potential effects on 
reproduction and development, and an evaluation of the pathology of the 
endocrine organs following short- and long-term exposure. These studies 
revealed no endocrine effects due to flucarbazone-sodium.
    9. Other studies--i. An acute neurotoxicity screening study in rats 
established an overall NOAEL for males and females of 500 mg/kg based 
on transient neurobehavioral effects. Evidence of toxicity was only 
slight at a limit dose of 2,000 mg/kg and complete recovery occurred 
within 7 days following treatment.
    ii. A subchronic neurotoxicity screening study in rats established 
an overall NOAEL of 2,000 ppm for males (equal to 147 mg/kg bwt/day) 
and 20,000 ppm (equal to 1,736 mg/kg bwt/day) for females based on a 
slight decrease in body weight and food consumption. The NOAEL for 
microscopic lesions was 20,000 ppm for males and females, the highest 
dose tested (HDT). There was no evidence of neurotoxicity at any 
dietary level.
    iii. A plaque-forming-cell assay (to investigate 
immunotoxicological potential) was performed on rats after a 4-week 
dietary exposure. The NOAEL of 20,000 ppm (equivalent to 2,205 and 
2,556mg/kg bwt/day in males and females, respectively) was based on the 
lack of specific effects in the HGT.
    iv. The immunotoxicity potential of flucarbazone-sodium was 
additionally investigated in antibody plaque-cell forming assays and in 
assays examining splenic T-cells, B-cells, and NK-cells after 4-week 
dietary administrations in male and female rats at levels up to and 
including 1,000 mg/kg bwt/day. There was no statistically significant 
effect on the humoral immune system and no effects on splenic cell 
populations, cell-mediated immune response, or the innate immune 
response in males or females. The NOAEL for immunotoxicity from these 
studies was 1,000 mg/kg bwt/day, the immunotoxicity limit dose.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. Estimates of chronic dietary exposure 
to residues of flucarbazone-sodium utilized the proposed tolerance-
level residues for wheat forage, wheat hay, wheat straw, wheat grain, 
meat, liver, and milk of 0.30, 0.10, 0.05, 0.01, 0.01, 1.50, and 0.005 
ppm, respectively. Other assumptions were that 100% of the target crop 
would be treated with flucarbazone-sodium and that no loss of residue 
would occur due to processing and/or cooking. A chronic reference dose 
(RfD) of 0.36 milligrams/kilogram/day (mg/kg/day) was assumed based on 
the NOAEL of 35.9 mg/kg/day from the one year dog feeding study. A 
safety factor of 100 was used based on interspecies extrapolation (10x) 
and intraspecies variability (10x). Using these conservative 
assumptions, dietary residues of flucarbazone-sodium contribute 
0.006659 mg/kg/day (2% of the RfD) for children 1-6 years, the most 
sensitive sub-population. For the U.S. population, the exposure was 
0.002891 mg/kg/day (1% of the RfD). For acute dietary exposure, the 
same conservative assumptions were made. Based on the NOAEL of 300 mg/
kg/day from the rabbit developmental toxicity study, an acute RfD of 
3.0 mg/kg/day was used to calculate the acute dietary risk to the most 
exposed subgroup: females, 13 to 50 years old. The acute dietary 
exposure from food to flucarbazone-sodium will occupy <1% of the RfD 
for females, 13 to 50 years old.
    ii. Drinking water. Given the post-emergence application pattern, 
low use rates and rapid soil degradation of flucarbazone-sodium, the 
risk of ground and surface water contamination and exposure via 
drinking water is negligible. The surface water model

[[Page 43417]]

generic expected environment concentration (GENEEC) and the ground 
water model (SCI-GROW) were used to determine whether drinking water 
from surface or ground water sources represented a worst-case exposure 
scenario. These models predict residues of flucarbazone-sodium would be 
higher in surface water. Assuming a worst-case GENEEC scenario where 
residues of flucarbazone-sodium occur in surface water used for 
drinking water at the highest predicted acute and chronic 
concentrations, the risk from exposure to residues of flucarbazone-
sodium are well within EPA's acceptable limits.
    The GENEEC model predicted an acute surface water concentration of 
flucarbazone-sodium of 1.45 [mu]g/L. Assuming a 70 kilogram (kg) adult 
drinks 2 liters/day containing 1.45 [mu]g/L, the acute exposure would 
be 0.0000414 mg/kg/day for adults. Assuming a 10 kg child drinks 1 
liter/day containing 1.45 [mu]g/L, the exposure would be 0.000145 mg/
kg/day. Based on the NOAEL of 300 mg/kg/day from the rabbit 
developmental toxicity study and assuming a safety of 100 (10x for 
interaspecies variability and 10x for interspecies extrapolation), the 
MOE for adults of 72,500 and for children of 20,700 do not exceed EPA's 
level of concern for adults or children. This assessment is based on 
the GENEEC highest predicted acute concentration of flucarbazone-sodium 
in drinking water using worst-case assumptions.
    Using GENEEC, the highest predicted chronic (60-day exposure) 
concentration of flucarbazone-sodium was 1.44 [mu]g/L. EPA interim 
policy recommends that the 60-day GENEEC value to be divided by an 
adjustment factor of 3 to obtain a value for chronic risk assessment 
calculations. Therefore, a surface water value of 0.48 [mu]g/L was used 
for chronic risk assessment. Assuming a 70 kg adult consumes 2 liters 
(L) of water per day containing 0.48 [mu]g/L of flucarbazone-sodium 
residues for a period of 70 years, less than 0.004% of the RfD was 
consumed from residues of flucarbazone-sodium in surface water used for 
drinking water (worst-case scenario). For a 10 kg child drinking 1 L of 
water per day containing 0.48 [mu]g/L of flucarbazone-sodium residues, 
only 0.01% of the RfD was consumed by drinking water.
    2. Non-dietary exposure. There are no current non-food uses for 
flucarbazone-sodium registered under the Federal Insecticide,Fungicide, 
and Rodenticide Act (FIFRA), as amended. No non-food uses are proposed 
for flucarbazone-sodium. No non-dietary exposures are expected for the 
general population.

D. Cumulative Effects

    Flucarbazone-sodium falls into the category of sulfonamide 
herbicides. There is no information to suggest that any of this class 
of herbicides has a common mechanism of mammalian toxicity or even 
produce similar effects so it is not appropriate to combine exposures 
of flucarbazone-sodium with other herbicides. Arvesta Corporation is 
considering only the potential risk of flucarbazone-sodium.

E. Safety Determination

    1. U.S. population. As presented previously, the exposure of the 
U.S. general population to flucarbazone-sodium is low, and the risks, 
based on comparisons to the reference dose, are minimal. The margins of 
safety from the use of flucarbazone-sodium are well within EPA's 
acceptable limits. Arvesta Corporation concludes that there is a 
reasonable certainty that no harm will result to the U.S. population 
from aggregate exposure to flucarbazone-sodium residues.
    2. Infants and children. The complete toxicological data base 
including the developmental toxicity and 2-generation reproduction 
studies were considered in assessing the potential for additional 
sensitivity of infants and children to residues of flucarbazone-sodium. 
The developmental toxicity studies in rats and rabbits revealed no 
increased sensitivity of rats or rabbits to in-utero exposure to 
flucarbazone-sodium. The 2-generation reproduction study did not reveal 
any increased sensitivity of rats to in-utero or postnatal exposure to 
flucarbazone-sodium. Furthermore, none of the other toxicology studies 
revealed any data demonstrating that young animals were more sensitive 
to flucarbazone-sodium than adult animals. The data taken collectively 
clearly demonstrate that application of a Food Quality Protection Act 
(FQPA) uncertainty factor for increased sensitivity of infants and 
children is not necessary for flucarbazone-sodium.

F. International Tolerances

    A default Maximum Residue Limit (MRL) of 0.01 ppm has been 
established in Canada for residues of flucarbazone-sodium and its N-
desmethyl metabolite on wheat grain. This value is consistent with the 
tolerance being proposed in the United States on wheat grain. There are 
no harmonized MRLs at the European Union level and no Codex MRLs for 
this compound on wheat at present. Therefore, no compatibility issues 
exist with Codex in regard to the proposed U.S. tolerances.

[FR Doc. 05-14736 Filed 7-26-05; 8:45 am]
BILLING CODE 6560-50-S