[Federal Register Volume 69, Number 129 (Wednesday, July 7, 2004)]
[Notices]
[Pages 40920-40927]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-15212]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2004-0181; FRL-7364-7]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket ID number OPP-2004-0181, must be 
received on or before August 6, 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

[[Page 40921]]

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-2004-0181. The official public docket 
consists of the documents specifically referenced in this action, any 
public comments received, and other information related to this action. 
Although, a part of the official docket, the public docket does not 
include Confidential Business Information (CBI) or other information 
whose disclosure is restricted by statute. The official public docket 
is the collection of materials that is available for public viewing at 
the Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall 2, 1921 Jefferson Davis Hwy., Arlington, VA. This 
docket facility is open from 8:30 a.m. to 4 p.m., Monday through 
Friday, excluding legal holidays. The docket telephone number is (703) 
305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
     An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. 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. 
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 on 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-2004-0181. 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-2004-0181. 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

[[Page 40922]]

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-2004-0181.
    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-2004-0181. 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: June 22, 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 amd Company

PP 0F6152

     EPA has received a pesticide petition PP 0F6152 from E. I. du Pont 
de Nemours and Company, DuPont Agricultural Products, Barley Mill 
Plaza, 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 part 180, by establishing a tolerance for residues of 
thifensulfuron methyl: Methyl-3-[[[[(4-methoxy-6-methyl-1,3,5-triazin-
2-yl)amino]carbonyl]amino sulfonyl]-2-thiophenecarboxylate in or on the 
raw agricultural commodity imazethapyr tolerant canola seed at 0.02 
parts per million (ppm), cotton seed at 0.02 ppm, cotton gin trash at 
0.02 ppm and CDC triffid flax at 0.02 ppm. EPA has determined that the 
petition contains data or information regarding the elements set forth 
in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues of 
thifensulfuron methyl is adequately understood. Plant metabolism 
studies on wheat, corn, and soybeans were conducted. No significant 
difference in metabolic profile was observed. The plant metabolism 
studies in wheat and in corn were conducted with 14C-labeled 
thiophene and triazine rings to follow the degradation pathway from the 
two most stable portions of thifensulfuron methyl. The metabolism in 
those plants shows similar patterns and involves cleavage of the urea 
bridge and metabolism of the methoxy group on the triazine ring and 
hydrolysis of the methyl ester group on the thiophene ring. The 
thiophene portion of thifensulfuron methyl in wheat degraded to 2-acid-
3-sulfonamide and 14C-polar compounds that further broke 
down to 14CCO2. The triazine ring of 
thifensulfuron methyl metabolized to triazine urea and triazine amine. 
In corn, the thiophene portion of thifensulfuron methyl degraded to 2-
acid-3-sulfonamide as well, and the triazine ring metabolized primarily 
to triazine urea and triazine amine. The primary thifensulfuron methyl 
metabolic pathways in soybean and wheat are the same. Minor differences 
in the formation and decline of the short-lived intermediate precursors 
to 2-acid-3 sulfonamide and O-demethyl triazine amine were found. These 
differences were not environmentally significant because of the very 
low levels of these intermediate metabolites in crops.
     Metabolism studies conducted with radioactive 14C-
thifensulfuron methyl

[[Page 40923]]

on wheat under field conditions showed no significant residues of 
thifensulfuron methyl or its degradation products (>0.01 ppm) in field 
wheat grain at maturity. Mature forage and straw total residues were 
0.80 to 0.45 ppm for the thiophene and triazine-labeled tests 
respectively. No single metabolite was greater than 0.06 ppm in the 
mature wheat. Major metabolites in wheat straw were thifensulfuron 
methyl, thifensulfuron methyl acid, 2-acid-3-sulfonamide, O-demethyl 
thifensulfuron methyl, triazine urea, and triazine amine.
     There were no detectable residues of thifensulfuron methyl or its 
transformation products in corn grain (<0.01 ppm) or foliage (<0.02 
ppm) at maturity. Analysis of earlier foliar samples showed extensive 
metabolism of thifensulfuron methyl. Among the residues detected were 
thifensulfuron methyl, 2-acid-3-sulfonamide, triazine urea, triazine 
amine, O-demethyl triazine urea, and O- demethyl triazine amine, 
however no thifensulfuron methyl acid was detected.
     Metabolism studies were conducted with soybeans under greenhouse 
conditions. There were no detectable residues (<0.01 ppm) in the bean 
or pods at either rate or label at final harvest. Analysis of earlier 
foliar samples showed extensive metabolism of thifensulfuron methyl. 
Among the residues detected were thifensulfuron methyl, thifensulfuron 
methyl acid, 2-ester-3-sulfonamide, 2-acid-3-sulfonamide, triazine 
amine, O-demethyl triazine amine.
     Two different crop rotation scenarios were investigated, one 
involving a bare ground application, the other one with a cover crop. 
No significant difference in metabolic profile was observed.
     A confined greenhouse crop rotation study (following application 
to bare soil) was conducted planting beets, peas, and sunflowers at 
either a 30-day or 120-day treatment-to-planting interval. The 
application rate used was 34.8-38 grams/active ingredient/acre (g a.i./
acre). There were no substantial residues (0.001 to 0.005 ppm) in food 
items (beet root, peas, sunflower seeds) in crops planted 30 or 120 
days following soil treatment. There were minor detectable residues 
(0.02 to 0.05 ppm) in animal feed items (beet foliage and sunflower 
foliage). Thifensulfuron methyl was the only component identified 
(0.002 ppm) in sunflower foliage 73 days after treating the soil. 
Thifensulfuron was the only major radiolabeled component observed in 
the treated soil at the 30-day crop planting interval.
     A confined greenhouse crop rotation study following treated wheat 
was conducted using beet root, peas, pea pods, and sunflower as 
following crops. The study used an application rate of 14.6 g a.i./
acre, and a 45 or 75 day treatment-to-planting interval. There were no 
substantial residues (less than 0.01 ppm) in food items (beet root, 
peas, pea pods, sunflower (seeds and heads)) in crops planted 45 or 75 
days following treated wheat incorporation into the soil. There were 
minor detectable residues in animal feed items. Pea and sunflower 
foliage contained 0.053-0.040 ppm and 0.015-0.008 ppm for the 45 and 75 
day planting, respectively. Small amounts of triazine amine (<0.032 
ppm), triazine urea, and O-demethyl triazine amine were identified in 
these fractions. Triazine urea was the major soil degradate at the 45 
and 75 days planting interval.
     Given the uniform lability of thifensulfuron methyl in plants, and 
that no residues above the limit of quantitation were found in treated 
canola plants with the ``Smart'' trait, it is unlikely that there would 
be any significant accumulation of metabolites in the harvested 
portions of treated canola and CDC triffid flax. No significant 
difference in metabolite distribution is anticipated for cotton use 
either. This is due to the significant soil interception that occurs 
during either a preemergence or postemergence application when 
thifensulfuron methyl is applied to small weeds for effective weed 
control.
    2. Analytical method. For wheat, barley, and soybeans, the 
analytical methods use liquid chromatography and a photoconductivity 
detector for thifensulfuron methyl. Coupled with extraction, cleanup 
and isolation procedures, these methods provide a means of determining 
thifensulfuron methyl in soybeans and in wheat and barley straw with a 
detection limit of 50 parts per billion (ppb) nanogram/gram (50 ng/g), 
based on a 5-gram sample (soybeans) or a 10-gram sample (wheat and 
barley).
     For corn forage and whole ears, an analytical method uses liquid 
chromatography and a photoconductivity detector for thifensulfuron 
methyl. Coupled with extraction, cleanup and isolation procedures, this 
method provides a means of determining thifensulfuron methyl in kernels 
with a detection limit of 20 ppb (20 ng/g), based on a 25-gram sample, 
and 50 ppm (50 ng/g) based on a 10 gram sample for green forage and 
whole ears. For determination of thifensulfuron methyl residues in corn 
processed fractions (processed corn oil and processed corn meal), the 
method uses HPLC with UV detection at 254 nm. This method provides a 
means to determine thifensulfuron methyl at levels as low as 0.02 ppm, 
based on a 10 gram sample.
     Thifensulfuron methyl residues in canola and flax samples were 
determined by an analytical method based on the use of liquid 
chromatography with eluent and column switching with photometric 
detection at 254 nm at levels as low as 0.02 ppm (limit of 
quantitation) using a 5 gram sample.
     Residues in cotton seed and gin trash were determined based on the 
use of column-switching liquid chromatography with detection via 
positive ion electrospray mass spectroscopy. The limit of quantitation 
was determined to be 20 ng/g and the limit of detection was estimated 
to be 6 ng/g, based on a 5 gram sample.
    3. Magnitude of residues--a. Wheat and barley grain and straw. 
Field tests were conducted on wheat and on barley at 20 representative 
sites in the United States. Residues of thifensulfuron methyl were 
determined in wheat and barley grain and straw after single 
postemergence applications of thifensulfuron methyl at rates of 0-0.28 
kg a.i./hectare (a.i./ha) in wheat and 0-0.14 kg a.i./ha in barley. The 
pre-harvest interval (PHI) was 41-140 days for the wheat grain and 
straw samples, 49-116 days for barley grain, and 60-89 days for barley 
straw. No quantifiable residues (<0.02 ppm for grain, <0.05 ppm for 
straw) were found in any samples.
     In separate studies, wheat was treated with thifensulfuron methyl 
at a rate of 0.50 oz. a.i./acre or higher, and harvested at PHIs 
ranging from 25-42 days. No thifensulfuron methyl residues were 
detected in wheat grain (<0.02 ppm) or straw (<0.05 ppm) in any of the 
trials. Barley was treated with thifensulfuron methyl at a rate of 0.50 
oz a.i./acre. Samples of mature barley grain and straw were taken from 
the test plots at a PHI of approximately 40 days after the test 
substance was applied. All results were below the established tolerance 
of 0.05 ppm for grain, and 0.1 ppm for straw.
    b. Corn grain, forage and fodder. Field tests were conducted in the 
U.S. at 15 sites representative of the major U.S. corn growing regions. 
Tests included two decline studies. Residues of thifensulfuron methyl 
were determined in corn grain, forage, and fodder after a single 
postemergent application of thifensulfuron methyl at rates from 0 to 
0.070 kg a.i./ha. PHIs were 80-154 days for the grain sample, 0-97 days 
for forage, and 82-154 days for fodder. No

[[Page 40924]]

residues above the quantitation limit (<0.02 milligrams/kilogram (mg/
kg) for grain, <0.05 mg/kg for forage/fodder) were found in any grain 
or fodder samples. Residues in forage declined very rapidly with time. 
Even with treatment, at several times the typical use rate, residues 
were below the limit of quantitation within 14 days after treatment. In 
another study, plots were treated with thifensulfuron methyl at rates 
of 0.5, 1.0, and 2.0 oz a.i./acre. No thifensulfuron methyl was 
detected (quantitation limit of 0.02 ppm) in grain from the 2.0 oz. 
sample. No residues of thifensulfuron methyl were detected in the 
processed fractions (corn oil and corn meal).
    c. Soybeans. A study was conducted to evaluate the magnitude of 
residues of thifensulfuron methyl in soybeans at either 0.125 oz a.i./
acre or 0.25 oz a.i./acre. All applications were made approximately 60 
days before harvest and were postemergence foliar broadcast. All 
thifensulfuron methyl residues in treated soybeans were below the limit 
of quantitation of 0.050 ppm; the current tolerance for thifensulfuron 
methyl in soybeans is 0.1 ppm.
    d. Oat grain and straw. In a study using either 0.45 oz. a.i./acre 
or 0.90 oz. a.i./acre thifensulfuron methyl on oats, samples of mature 
oat grain and straw were taken from plots at preharvest intervals 
ranging from 39-57 days after the application of the test substance. 
Results show that all residues for thifensulfuron methyl were below the 
limit of quantitation (0.0055 ppm for oat grain, and 0.018 ppm for oat 
straw).

    e. Canola and flax. Magnitude of residue studies were conducted on 
a variety of canola containing the ``Smart'' trait at 15 test sites, 
and on CDC triffid flax at 11 test locations. All treatment plots 
received an application at a rate of 15 or 30 g a.i./ha as a broadcast 
foliar application. The canola variety containing the ``Smart'' trait 
ranged from cotyledon up to the 8 leaf stage at application. CDC 
triffid flax staging at application ranged from 5 to 20 cm in height. 
No thifensulfuron methyl residues were found above the limit of 
quantitation of 0.02 ppm in any seed samples treated with the test 
substance.
    f. Cotton seed and gin trash. Magnitude of residue studies were 
also conducted to determine residues of thifensulfuron methyl in cotton 
seed and cotton gin trash at nine test sites. The study consisted of 
three treatments. Treatment 1: One broadcast application at 0.45 oz 
a.i./acre, applied approximately 14-days prior to planting. Treatment 
2: One broadcast application at 0.45 oz a.i./acre, applied pre-plant, 
on the day of planting. Treatment 3: One broadcast application at 2.25 
oz. a.i./acre, applied pre-plant, the day of planting. The anticipated 
target PHI was approximately 120-days after the last application of the 
test substance; actual PHIs ranged from 123-196 days. The 
experimentally determined limit of quantitation was 20 ppb for both 
analytes. The limit of detection was estimated to be 6 ppb. No 
thifensulfuron methyl residues were found above the limit of 
quantitation of 0.02 ppm in any cotton seed and cotton gin trash 
samples treated with the test substance.

B. Toxicological Profile

    1. Acute toxicity. Based on EPA criteria, technical thifensulfuron 
methyl is in acute toxicity Category IV for oral and inhalation routes 
of exposure, and for eye irritation. Thifensulfuron methyl is in acute 
toxicity Category III for the dermal route of exposure and for dermal 
irritation. It is not a skin sensitizer.

------------------------------------------------------------------------
 
------------------------------------------------------------------------
Acute oral toxicity in rats                 LD50 >5,000 mg/kg
------------------------------------------------------------------------
Acute dermal toxicity in rabbits            LD50 >2,000 mg/kg
------------------------------------------------------------------------
Acute inhalation toxicity in rats           LD50 >7.9 milligrams/Liter
                                             (mg/L)
------------------------------------------------------------------------
Primary eye irritation in rabbits           Minimal effects reversed
                                             within 24 hours
------------------------------------------------------------------------
Primary dermal irritation in rabbits        Effects reversed within 48
                                             hours
------------------------------------------------------------------------
Dermal sensitization in guinea pigs         Non-senitizer
------------------------------------------------------------------------

    2. Genotoxcity. Technical thifensulfuron methyl has shown no 
genotoxic or mutagenic activity in the following in vitro and in vivo 
tests:
     In vitro Mutagenicity Ames Assay Negative
     In vitro mutagenicity Chinese hampster ovary/hypoxanthine 
guanine phophoribosyl transferase (CHO/HPRT) Assay Negative
     In vitro unscheduled DNA synthesis negative
     In vivo micronuclei induction (Rat) negative
     Thifensulfuron methyl was not mutagenic with or without metabolic 
activation in an in vitro bacterial gene mutation assay using 
Salmonella typhimurium. Thifensulfuron methyl also was not mutagenic in 
the in vitro CHO/HPRT assay at concentrations up to 2,712 mg/L (in 
Chinese hamster ovary cells). In cultured primary rat hepatocytes, 
thifensulfuron methyl was negative for the induction of unscheduled DNA 
synthesis up to 2,712 mg/L.
     An in vivo chromosome aberration study was conducted on rats. This 
included the assessment of chromosome aberrations by metaphase analysis 
in bone marrow of male and female rats. Thifensulfuron methyl did not 
induce cytogenic damage in bone marrow cells at a dose of 5,000 mg/kg.
    3. Reproductive and developmental toxicity. The results of a series 
of studies indicated that there were no reproductive, developmental or 
teratogenic hazards associated with the use of thifensulfuron methyl. 
In a 1-generation reproduction study in rats, the suggested no observed 
effect level (NOEL) was 7,500 ppm (559 mg/kg/day males, 697 mg/kg/day 
females). In a rat multigeneration reproduction study, the NOEL for 
reproductive effects of thifensulfuron methyl in adult rats and their 
offspring was 2,500 ppm, the highest dietary level tested. This level 
was based on the absence of significant compound related effects 
observed in this study and is equivalent to 175-180 mg/kg/day in adult 
male rats and 212-244 mg/kg/day in adult female rats. There were no 
effects on fertility, lactation, litter size, or pup survival. 
Thifensulfuron methyl is not considered a reproductive toxin.
     In studies conducted to evaluate developmental toxicity potential, 
thifensulfuron methyl was neither teratogenic nor uniquely toxic to the 
conceptus (i.e., not considered a developmental toxin). In the rat 
study, there was evidence of maternal toxicity (small decrease in body 
weight gain) and developmental toxicity (increase in sum of fetuses 
with developmental variations and variations due to retarded 
development) at a dose level of 800 mg/kg/day. No significant 
indications of maternal or fetal toxicity were evident at the other 
dose levels (0, 30, and 200 mg/kg/day). Therefore, the maternal and 
developmental no observed adverse effect level (NOAEL) for rats was 
considered to be 200 mg/kg/day. Upon review by the EPA, the NOEL was 
set at 159 mg/kg/day. In the rabbit developmental toxicity study, there 
was slight maternal toxicity (decreased body weight gain) at a dose of 
650 mg/kg/day. No significant indications of maternal toxicity were 
evident at the lowest dose level (30 mg/kg/day). No compound-related 
effects on fetal weights or the incidences of malformations or 
variations were seen at any dose. The maternal NOEL was 200 mg/kg/day 
and the developmental NOEL was 650 mg/kg/day for rabbits dosed with 
thifensulfuron methyl by gavage on gestation days 7-19. Upon review by 
the

[[Page 40925]]

EPA, the maternal NOEL was set at 158 mg/kg/day and the developmental 
NOEL 511 mg/kg/day.
    4. Subchronic toxicity. The most sensitive species to subchronic 
exposure of thifensulfuron methyl was the rat. The findings show that 
the NOEL for thifensulfuron methyl were 100 ppm for male and female 
rats (90-day dietary). These levels were based on the decreased body 
weight and food efficiency noted in the 2,500 and 7,500 parts per 
million (ppm) groups. This concentration is equivalent to 7 and 9 mg/
kg/day in male and female rats, respectively. For mice, in both the 4-
week range-finding and the 90-day studies, the NOEL for both male and 
female mice under the conditions of this study was 7,500 ppm; this was 
based on the lack of compound-related effects at the highest 
concentration. 7,500 ppm is equivalent to 1,427 mg/kg/day in male mice 
and 2,287 mg/kg/day in female mice. The NOEL for subchronic (90-day 
dietary) exposure in dogs was 1,500 and 7,500 ppm in male and female 
dogs, respectively. The NOELs were equivalent to 40.4 mg/kg/day in male 
dogs and 159.7 mg/kg/day in female dogs. These levels were based on 
lower body weight in males and a lack of adverse effects in females at 
7,500 ppm, the highest concentration tested. In females, a compound-
related decrease in body weight was observed at 7,500 ppm but was not 
considered adverse, based on the small magnitude of effect. Therefore, 
the NOEL in males and females was 1,500 ppm (26.1 mg/kg/day female, 
40.4 mg/kg/day male). No compound-related pathologic lesions were 
observed and no target organ was identified in all of the above tests.
    5. Chronic toxicity. The NOEL for chronic (18-month dietary) 
exposure in mice was 7,500 ppm (equivalent to 979 and 1,312 mg/kg/day 
in male and female mice, respectively). No biologically significant 
compound-related effects were seen in male or female mice at 7,500 ppm, 
the highest concentration tested. Thifensulfuron methyl was not an 
oncogen in mice.
     The NOEL for chronic (2-year dietary) exposure in rats was 500 ppm 
(20 and 26 mg/kg/day in male and female rats, respectively). The NOEL 
was based on body weight effects in male and female rats at 2,500 ppm. 
The NOEL in female rats was 25 ppm (1.3 mg/kg/day) based on a non-
adverse reduction in serum sodium concentration at 500 ppm. 
Thifensulfuron methyl was not an oncogen in rats.
     In a 1-year feeding study in dogs, the NOEL of thifensulfuron 
methyl was 750 ppm in male and female beagle dogs (equivalent to 19.7 
mg/kg/day males and 22.5 mg/kg/day females), based on decreased body 
weights, body weight gains, and food efficiency in females and 
increased liver with gall bladder weights in males, all at 7,500 ppm. 
The liver weight effects in males are not considered to be adverse 
effects; therefore, the lowest observed effect level (LOEL) was 
considered to be 7,500 ppm (195.3 mg/kg/day) in male dogs and 750 ppm 
(22.5 mg/kg/day) in female dogs.
    6. Animal metabolism. The proposed major metabolic pathway for 
thifensulfuron methyl involved hydrolysis to 2-ester-3-sulfonamide 
(which may chemically condense to yield thiophene sulfonimide) or non-
specific esterase activity to yield thifensulfuron methyl acid. The 
tissue data did not indicate potential retention or accumulation of 
thifensulfuron methyl or its metabolites.
     Rats were dosed with two radioactive forms of thifensulfuron 
methyl (14C-thiophene and 14C-triazine). In the 
thiophene study, the thifensulfuron methyl was primarily excreted 
unchanged by rats following low dose (20 mg/kg), low dose following 21-
days dietary preconditioning 100 ppm, and high dose (2,000 mg/kg) 
routines. From 70% to 85% of the excreted radioactivity was 
thifensulfuron methyl. The urine was the primary excretion route and 
contained from 71% to 92% of the original dose from the low and low-
dose preconditioned groups. Combined urinary and fecal elimination was 
rapid, with over 90% of excretion completed by 48 hours after dosing 
for both low-dose groups. The high-dose group peak elimination was 
delayed by approximately 24 hours compared to the other dose levels. 
Tissue radioactivity levels were low at sacrifice (96 hours after 
dosing) for all dosing groups with no enhanced retention of 
radioactivity by any organ or tissue. Mass spectral analysis confirmed 
thifensulfuron methyl as the primary radiolabeled excretion product. 
Structural confirmation was also obtained for the 2-ester-3-sulfonamide 
metabolite. In the triazine study, thifensulfuron methyl was excreted 
primarily unchanged in urine and feces by male and female rats after 
administration of approximately 2,000 mg/kg by oral gavage. Urine was 
the primary route of excretion, averaging 58.7% of the dose in males 
and 75.5% in females. Fecal excretion of the dose averaged 21.2% for 
the male rats and 15.8% for the females. Greater than 50% of the dose 
was excreted by 48 hours post-dosing. Essentially no elimination of the 
dose as radiolabeled CO2 or volatile compounds occurred. 
These results are similar to those reported on the thiophene-labeled 
thifensulfuron methyl. Intact thifensulfuron methyl was identified by 
mass spectrometry as the principal radioactive compound in urine (>94%) 
and feces (>77%). Three minor metabolites, each less than 3% of the 
dose, were identified in urine and feces by chromatographic retention 
comparison; they were thifensulfuron methyl acid, O-Demethyl 
thifensulfuron methyl, and triazine amine.
     Results from a metabolism study with two radioactive forms of 
thifensulfuron methyl (14C-triazine and 14C-
thiophene) in lactating goats show that most of the dosed radioactivity 
was rapidly excreted (primarily in the urine) and recovered as intact 
thifensulfuron methyl. Radioactivity in the milk (0.1-0.2 ppm) was 
comprised of mostly intact thifensulfuron methyl and a small amount of 
triazine amine and several very minor metabolites. Radioactivity did 
not accumulate in the tissues. After its absorption, the major 
metabolic pathway involved cleavage of the carboxyl ester linkage, 
resulting in the formation of thifensulfuron methyl acid. Oxidative O-
demethylation occurred to a limited extent.
     There were no significant levels of unique plant metabolites of 
thifensulfuron methyl found in food or feed products at crop maturity. 
Hence, toxicity testing of other degradation products of thifensulfuron 
methyl is not needed.
    7. Metabolite toxicology. There is no evidence that the metabolites 
of thifensulfuron methyl as identified in 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 thifensulfuron methyl 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 thifensulfuron 
methyl has an adverse effect on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure. The chronic reference dose (RfD) of 0.013 mg/
kg/day is based on the NOEL of 1.25 mg/kg/day from a 2-year rat feeding 
study and a 100X safety factor. The acute RfD of 1.59 mg/kg/ day is 
based on the NOEL of 159

[[Page 40926]]

mg/kg/day from a rat developmental study and a 100X safety factor.
    i. Food--a. Chronic dietary exposure assessment dietary exposure, 
resulting from the proposed use of thifensulfuron methyl on barley, 
canola, cotton, flax, field corn, oats, soybeans and wheat, is well 
within the acceptable limits for all sectors of the population, as 
predicted by both the Chronic and Acute Modules of the Dietary Exposure 
Evaluation Model (DEEMTM, Novigen Sciences, Inc., 1999 
Version 6.74). The percentage or proportion of a crop that is treated 
can have a significant effect on the exposure profile. In this case, it 
was assumed for the crop that 100% was treated with thifensulfuron 
methyl. Based on a comparison with the use profile for most other 
herbicides, this is an extremely conservative estimate.
     The predicted chronic exposure for the U.S. population subgroup 
was 0.000140 milligrams/kilogram body weight/day (mg/kg bwt/day). The 
population subgroup with the highest predicted level of chronic 
exposure was the non-nursing infants subgroup with an exposure of 
0.000382 mg/kg bwt/day. Based on a chronic NOEL of 1.25 mg/kg bwt/day 
and a 100-fold safety factor, the chronic reference dose (cRfD) would 
be 0.013 mg/kg bwt/day. For the U.S. population, the predicted exposure 
is equivalent to 1.1% of the cRfD. For the population subgroup with the 
highest level of exposure (non-nursing infants), the exposure would be 
equivalent to 2.9% of the cRfD. Because the predicted exposures, 
expressed as percentages of the cRfD, are well below 100%, there is 
reasonable certainty that no chronic effects would result from dietary 
exposure to thifensulfuron methyl.
    b. Acute dietary exposure. The predicted acute exposure for the 
U.S. population subgroup was 0.000364 mg/kg bwt/day (95th 
percentile). The population subgroup with the highest predicted level 
of acute exposure was the non-nursing infants subgroup with an exposure 
of 0.000846 mg/kg bwt/day (95th percentile). Based on an 
acute NOEL of 159 mg/kg bwt/day and a 100-fold safety factor, the acute 
reference dose (aRfD) would be 1.59 mg/kg bwt/day. For the U.S. 
population the predicted exposure (at the 95th percentile) 
is equivalent to 0.02% of the aRfD. For the population subgroup with 
the highest level of exposure (non-nursing infants subgroup), the 
exposure (at the 95th percentile) would be equivalent to 
0.05% of the aRfD. Because the predicted exposures, expressed as 
percentages of the aRfD, are well below 100%, there is reasonable 
certainty that no acute effects would result from dietary exposure to 
thifensulfuron methyl.
    ii. Drinking water. Surface water exposure was estimated using the 
Generic Expected Environmental Concentration (GENEEC) model. Ground 
water exposures were estimated using Screening Concentration in Ground 
water (SCI-GROW).
     EPA uses drinking water levels of comparison (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. 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 DWLOCs are 56 ppm (parts per million) for the U.S. 
population and 16 ppm for the subpopulation with the highest exposure 
(non-nursing infants). The estimated maximum concentration of 
thifensulfuron methyl in surface water (1.2 ppb or parts per billion) 
derived from GENEEC is much lower than the acute DWLOCs. Therefore, one 
can conclude with reasonable certainty, that residues of thifensulfuron 
methyl in drinking water do not contribute significantly to the 
aggregate acute human health risk.
     The chronic DWLOCs are 0.45 ppm for the U.S. population and 0.13 
ppm for the subpopulation with the highest exposure (non-nursing 
infants). These DWLOC values are substantially higher than the GENEEC 
56-day estimated environmental concentration of 0.65 ppb for 
thifensulfuron methyl in surface water. Therefore, one can conclude 
with reasonable certainty, that residues of thifensulfuron methyl in 
drinking water do not contribute significantly to the aggregate chronic 
human health risk.
    2. Non-dietary exposure. Thifensulfuron methyl is not registered 
for any use which could result in non-occupational or non-dietary 
exposure to the general population.

D. Cumulative Effects

     Thifensulfuron methyl belongs to the sulfonylurea class of crop 
protection chemicals. Other structurally similar compounds in this 
class are registered herbicides. However, the herbicidal activity of 
sulfonylureas is due to the inhibition of acetolactate synthase (ALS), 
an enzyme found only in plants. This enzyme is part of the biosynthesis 
pathway leading to the formation of branched chain amino acids. Animals 
lack ALS and this biosynthetic pathway. This lack of ALS contributes to 
the relatively low toxicity of sulfonylurea herbicides in animals. 
There is no reliable information that would indicate or suggest that 
thifensulfuron methyl has any toxic effects on mammals that would be 
cumulative with those of any other chemical.

E. Safety Determination

    1. U.S. population. Thifensulfuron methyl is the active ingredient 
in two DuPont herbicides with new proposed uses on the following 
commercial crops: Imazethapyr tolerant canola, cotton and CDC triffid 
flax. There are no residential uses for any thifensulfuron methyl 
containing herbicides. Based on data and information submitted by 
DuPont, EPA previously determined that the establishment of tolerances 
of thifensulfuron methyl on the following raw agricultural commodities 
would protect the public health, including the health of infants and 
children:
     Barley: grain, straw
     Oats: grain, straw
     Wheat: grain, straw
     Field corn: grain, fodder
     Soybeans
     Forage
     Establishment of new tolerances for thifensulfuron methyl on 
canola seed at 0.02 ppm, cotton seed at 0.02 ppm, cotton gin trash at 
0.02 ppm, and flax at 0.02 ppm will not adversely impact public health.
     Based on the completeness and reliability of the toxicology data 
base and using the conservative assumptions presented earlier, EPA has 
established an RfD of 0.013 mg/kg/day. This was based on the NOEL for 
the chronic rat study, females (1.25 mg/kg/day) and a 100-fold safety 
factor. It has been concluded, that the aggregate exposure was 
approximately 1.1% of the RfD. Generally, exposures below 100% of the 
RfD are of no concern because it represents the level at or below which 
daily aggregate dietary exposure over a lifetime will not pose 
appreciable risk to human health. Thus, there is reasonable certainty 
that no harm will result from aggregate exposures to thifensulfuron 
methyl residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of thifensulfuron 
methyl, data from the previously discussed developmental and, 
multigeneration reproductive toxicity studies were considered.
     Developmental studies are designed to evaluate adverse effects on 
the developing organism resulting from pesticide exposure during 
prenatal development. Reproduction studies provide information relating 
to

[[Page 40927]]

reproductive and other effects on adults and offspring from prenatal 
and postnatal exposures to the pesticide. The studies with 
thifensulfuron methyl demonstrated no evidence of developmental 
toxicity at exposures below those causing maternal toxicity. This 
indicates that developing animals are not more sensitive to the effects 
of thifensulfuron methyl administration than adults.
     FFDCA section 408 provides that EPA may apply an additional 
uncertainty factor for infants and children in the case of threshold 
effects to account for prenatal and postnatal toxicity and the 
completeness of the data base. Based on current toxicological data 
requirements, the data base for thifensulfuron methyl relative to 
prenatal and postnatal effects for children is complete. In addition, 
the NOEL of 1.25 mg/kg/day in the chronic rat study (and upon which the 
RfD is based) is much lower than the NOELs defined in the reproduction 
and developmental toxicology studies. The sub-population with the 
highest level of exposure was non-nursing infants (<1 yr), where 
exposure was less than 1% of the RfD. Based on these conservative 
analyses, there is reasonable certainty that no harm will result to 
infants and children from aggregate exposures to thifensulfuron methyl.

F. International Tolerances

     The MRL in Canada for thifensulfuron methyl on canola is 0.1 ppm. 
No Mexican or Codex MRLs exist for thifensulfuron methyl on canola. 
There are no Canadian, Mexican or codex MRLs for thifensulfuron methyl 
on cotton and flax.

[FR Doc. 04-15212 Filed 7-6-04; 8:45 am]
BILLING CODE 6560-50-S