[Federal Register: October 22, 2003 (Volume 68, Number 204)]
[Notices]               
[Page 60378-60382]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22oc03-91]                         

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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0257; FRL-7322-5]

 
Mesosulfuron-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-2003-0257, must be 
received on or before November 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:  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: tompkins.jim@epa.gov.

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

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

    1. Docket. EPA has established an official public docket for this 
action under docket ID number OPP-2003-0257. 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

[[Page 60379]]

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-2003-0257. 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-2003-0257. 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-2003-0257.
    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-2003-0257. 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: October 9, 2003.
Debra Edwards,
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 Bayer CropScience 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 1F6298

     EPA has received a pesticide petition (1F6298) from Bayer 
CropScience, 2

[[Page 60380]]

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 part 180 by establishing a 
tolerance for residues of methyl 2-[[[[(4,6-dimethoxy-2-pyrimidinyl) 
amino]carbonyl]amino-]sulfonyl]-4-[[(methylsulfonyl) 
amino]methyl]benzoate, CAS No. 208465-21-8 (Mesosulfuron-methyl, 
Company Code AE F130060) in or on the raw agricultural commodities 
wheat grain at 0.03, wheat forage at 0.60, wheat straw at 0.30, wheat 
hay at 0.06, wheat germ at 0.10, aspirated grain fractions at 0.25, and 
milled byproducts at 0.03 parts per million (ppm). EPA has determined 
that the petition contains data or information regarding the elements 
set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully 
evaluated the sufficiency of the submitted data at this time or whether 
the data support granting of the petition. Additional data may be 
needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of mesosulfuron-methyl in wheat 
has been investigated and is understood. Identification of the 
extractable residues in grain was not possible due to the extremely low 
residue levels. In mature straw, three metabolites were identified at 
very low levels in addition to the parent AE F130060. Demethylation of 
one methoxy group on the pyrimidyl ring led to methyl 2-[3-(4-hydroxy-
6-methoxy-pyrimidin-2-yl)ureidosulfonyl]-4-
methanesulfonamidomethylbenzoate. Cleavage of the sulfonylurea bridge 
formed the interim phenyl metabolite, methyl-4-
methanesulfonamidomethyl-2-sulfamoyl-benzoate, which further cyclised 
to 6-methanesulfonamidomethyl-1,2-benzisothiazol-3(2H)-one 1,1-dioxide. 
The same metabolites were also detected in green plants (forage stage) 
as the main components; however, the parent substance contributed to a 
higher proportion to the total radioactive residue. All metabolites 
detected in plants were also found in animal metabolism studies.
    2. Analytical method. Based on the results of the metabolism 
studies, the analytical target selected was the parent compound 
mesosulfuron-methyl (AE F130060). Extractable residues of AE F130060 
are extracted from the crop matrix by blending with a solution of 
acetonitrile, water and triethylamine. After filtration, the extract is 
partitioned with hexane, then concentrated to a reduced volume. The 
resulting solution is diluted with 0.01M formic acid, and partitioned 
with ethyl acetate. An aliquot of ethyl acetate is evaporated to 
dryness and reconstituted in acetonitrile/water. This acetonitrile/
water extract is analyzed by HPLC-MS/MS for AE F130060. For some forage 
samples, an additional solid phase extraction clean up was required to 
suppress matrix enhancement effects.
    3. Magnitude of residues. The metabolism studies with 14C-labelled 
mesosulfuron-methyl in wheat demonstrated that in general, low residues 
were detected in the plant samples. These results have been confirmed 
in a total of 24 North American residue field trials using a water 
dispersible granule (WG) formulation containing 75% weight/weight (w/w) 
mesosulfuron-methyl. The preparation was applied in a single 
application, at a rate of 25 g a.i./ha. Pre-harvest intervals were 
between 4 and 68 days, 21 and 96 days, 50 and 91 or 50 and 134 days 
respectively for forage, hay, straw and grain. Residues in forage and 
straw ranged from below the limit of quantitation (LOQ), (0.05 
milligrams/kilogram (mg/kg)) to 0.55 mg/kg and 0.25 mg/kg respectively. 
No residues above the LOQ of 0.05 mg/kg were observed in hay. Residues 
in grain ranged from below the LOQ (0.01 mg/kg) to 0.026 mg/kg. 
Tolerances for mesosulfuron-methyl are proposed at 0.6 mg/kg, 0.06 mg/
kg, 0.3 mg/kg and 0.03 mg/kg respectively, for wheat forage, hay, straw 
and grain. In a wheat processing study, residues of mesosulfuron-methyl 
in the grain reached 0.011 mg/kg following treatment of the wheat at 75 
g a.i./ha. This exaggerated rate is approximately 5 times the maximum 
proposed label rate. In the processed fractions, residues of 
mesosulfuron-methyl were 0.014 mg/kg, 0.045 mg/kg and 0.014 mg/kg 
respectively in shorts, wheat germ and bran. No mesosulfuron-methyl 
residues above the LOQ (0.01 mg/kg) were observed in flour or 
middlings. Concentration factors of 1.3, 4.2 and 1.3, respectively were 
estimated for shorts, wheat germ and bran. Therefore, tolerances are 
proposed at 0.1 mg/kg for wheat germ and 0.03 mg/kg for milled by-
products (shorts, middlings and bran). No tolerance is proposed for 
flour since there was no evidence of concentration. Therefore, the 
tolerance for wheat grain will cover flour. In the same study, samples 
of aspirated grain dust were collected and found to contain residues of 
0.23 mg/kg. Accordingly, a tolerance of 0.25 mg/kg is proposed for 
aspirated grain fractions. Although, wheat grain is fed to poultry, and 
cattle may be grazed on forage or fed grain, hay or straw, tolerances 
in meat, milk or eggs are not necessary because dietary burden 
calculations have demonstrated that quantifiable residues of 
mesosulfuron-methyl will not occur in animal tissues.

B. Toxicological Profile

    1. Acute toxicity. Mesosulfuron-methyl has very low acute toxicity 
to mammals by all tested routes of exposure. Both the oral and dermal 
LD50's in the rat are greater than 5,000 milligrams/kilogram 
body weight (mg/kg bwt). The acute inhalation LC50 (4-hour) 
is greater than 1.33 milligrams per liter (mg/L) air, the maximum 
attainable concentration. Mesosulfuron-methyl was not irritating to 
rabbit skin and only slightly irritating to the eye. Mesosulfuron-
methyl did not induce delayed contact hypersensitivity (skin 
sensitization) in the maximization test. Based on these results, 
mesosulfuron-methyl is expected to be in EPA Category III or IV for all 
routes of acute exposure.
    2. Genotoxicty. Testing for possible genotoxic properties of 
mesosulfuron-methyl in vivo and in vitro gave consistently negative 
results. The in vitro test battery included investigations for gene 
mutation in bacteria and mammalian cells, examination of chromosomal 
aberrations in Chinese hamster cells and testing for unscheduled DNA-
synthesis (UDS) in primary rat hepatocytes. The in vivo mouse 
micronucleus assay was also conducted. As all five tests were negative 
and no evidence for carcinogenicity was seen in life-time experiments 
in two species, results indicate that mesosulfuron-methyl does not 
possess significant genotoxic activity.
    3.  Reproductive and developmental toxicity. A two-generation 
reproduction study in rats was conducted with dietary dose levels of 0, 
160, 1,600 and 16,000 ppm of technical mesosulfuron-methyl. There were 
no treatment-related adverse effects of the test material in any groups 
up to and including 16,000 ppm in the P and F1 generation male or 
female rats. This included mortality, clinical observations, general 
behavior, body weights, body weight gain, feed consumption, estrus 
cycle, sperm production, fertility, parturition, lactation, organ 
weights or microscopic findings. Therefore, the no observed adverse 
effect level (NOAEL) for the F0 and F1 parental animals for toxicity 
and reproductive effects is 16,000 ppm. The NOAEL for toxicity, growth 
and development of the F1a, F1b, F2a, and F2b offspring is 16,000 ppm, 
equivalent

[[Page 60381]]

to a mean daily test substance intake of at least 1,175 and 1,388 mg/kg 
bwt for males and females, respectively.
     A rat developmental toxicity (teratogenicity) study was conducted 
with dose levels of 0, 100, 315 and 1,000 mg mesosulfuron-methyl/kg 
bwt. Treatment did not cause lethality or effects on body weight. There 
were no clinical signs of toxicity. Pregnancy indices were unaffected. 
No treatment-related effects were observed in fetuses upon external, 
internal or skeletal evaluation. Therefore, the no observed effect 
level (NOEL) for both maternal and embryo-fetal toxicity was the limit 
dose of 1,000 mg/kg. Mesosulfuron-methyl was not teratogenic in rats.
     The rabbit developmental toxicity (teratogenicity) study was 
conducted with dose levels of 0, 100, 315 and 1,000 mg mesosulfuron-
methyl/kg body weight/day. No treatment-related deaths or clinical 
signs were seen. There were no effects on body weight development. No 
treatment-related effects were observed in fetuses upon external, 
internal or skeletal examination. Therefore, the NOAEL for maternal and 
developmental toxicity was the limit dose of 1,000 mg/kg. Mesosulfuron-
methyl was not teratogenic in the rabbit. In reproductive and 
developmental toxicity studies, mesosulfuron-methyl gave no evidence of 
reproductive, embryo-fetal or neonatal toxicity. Therefore, the 
potential for reproductive toxicity-related to mesosulfuron-methyl is 
low.
    4. Subchronic toxicity. In a 90-day rat feeding study, groups of 10 
male and 10 female Wistar rats were fed diets containing either 0, 240, 
1,200, 6,000 or 12,000 ppm of mesosulfuron-methyl. The administration 
of mesosulfuron-methyl up to the limit dose of 12,000 ppm was well 
tolerated. There were no mortalities and no adverse clinical findings. 
Body weight gains and feed consumption were comparable in all groups. 
There were no adverse behavioral, neurological or ophthalmoscopic 
findings. There were no effects on organ weights or histopathology. The 
NOAEL for this study was considered to be 12,000 ppm, corresponding to 
a daily substance intake of 907.5 mg/kg bwt in males and 976.5 mg/kg in 
females.
     In a 90-day feeding study in mice, mesosulfuron-methyl was 
administered at dietary concentrations of 0, 140, 1,000, and 7,000 ppm. 
Leukocyte counts were slightly lower in males at 1,000 and 7,000 ppm. 
However, since there were no corresponding histopathology findings, in 
particular no compensatory effect in the bone marrow and no adverse 
clinical effects associated with this finding, the NOAEL was 7,000 ppm 
mesosulfuron-methyl, equivalent to daily intakes of 1,238 mg/kg bwt/day 
in males and 1,603 mg/kg bwt/day in females.
     Groups of 4 male and 4 female beagle dogs were administered 
mesosulfuron-methyl at dietary concentrations of 0, 2,000, 10,000, and 
20,000 mg/kg/ bwt/day for 13 consecutive weeks. Mesosulfuron-methyl at 
concentrations of up to 20,000 ppm did not affect the general health 
status, behavior, body weight development or food consumption in dogs. 
No adverse effects were seen in hematology or biochemistry at any dose. 
There were no treatment-related changes in organ weights or 
histopathology. The NOAEL was 20,000 ppm (equating to 648 mg/kg bwt/day 
for males and 734 mg/kg bwt/day for females).
    5.  Chronic toxicity. A 1-year study was conducted in beagle dogs 
at doses of 1, 400, 4,000 and 16,000 ppm in the diet. There were no 
treatment-related effects noted other than non-specific signs of 
stomach irritation in some high dose dogs. The NOAEL was considered to 
be 16,000 ppm, equivalent to 574 mg/kg of body weight per day.
     The oncogenic potential of mesosulfuron-methyl was examined in 
bioassays with rats and mice over dietary exposure periods of 24 months 
and 18 months, respectively.
     Dietary administration of technical mesosulfuron-methyl to groups 
of 80 male and 80 female Wistar rats at concentrations of 0, 160, 1,600 
or 16,000, ppm (corresponding to a daily substance intake of up to 865 
mg/kg bwt for males and 1,056 mg/kg bwt for females) did not cause 
clinical symptoms or changes in hematology or biochemistry. All 
neoplastic and non-neoplastic lesions noted in the study were 
considered to be incidental findings commonly noted in rats of this 
strain and age and not related to treatment. The NOAEL for the daily 
administration of technical mesosulfuron-methyl for 12 or 24 months to 
male and female Wistar rats is 16,000 ppm.
     Groups of 60 male and 60 female CD-1 mice were given dietary 
concentrations of 0, 80, 800, or 8,000 ppm technical mesosulfuron-
methyl for up to 78 weeks. Mesosulfuron-methyl was not tumorigenic and 
did not cause non-neoplastic lesions. Leukocyte counts were increased 
in males and females at 8,000 ppm and in males at 800 ppm. However, as 
there were no indications for any adverse clinical or morphological 
effects related to the increased leukocyte values (and decreased values 
were seen in the 90-day study), 800 ppm is considered to be the NOAEL 
in the 18-month study. The NOAEL is based on lower body weight gains in 
females at the high dose level. This is equivalent to a mean achieved 
intake of 103 and 130 mg test substance/kg bwt/day in males and 
females, respectively.
     Mesosulfuron-methyl is expected to be classified as ``Not Likely'' 
to be a carcinogen based on the lack of carcinogenic findings in rats 
and mice.
    6. Animal metabolism. Following a single oral administration of 
either 10 or 1,000 mg/kg mesosulfuron-methyl to rats, 95.1% of the dose 
was found in the excreta 24 hours post-dosing. Fecal excretion was 
predominant, while only 12.8% and 1.3% of the low and high dose, 
respectively, were found in the urine. The predominant excretion 
product was unchanged mesosulfuron-methyl (>68%). The main metabolic 
pathway was cleavage of the sulfonylurea-bridge leading to the 
pyrimidine moiety (2-amino-4,6-dihydroxypyrimidine) and the resulting 
phenyl moiety which further cyclised to 6-methanesulfonamidomethyl-1,2-
benzisothiazol-3(2H)-one 1,1-dioxide. Minor metabolic reactions 
observed were O-demethylation of the intact molecule at the pyrimidine 
moiety, cleavage of the sulfonylurea-bridge to form 4-hydroxy-6-
methoxypyrimidin-2-yl-urea, and additional O-demethylation to 4,6-
dihydroxypyrimidin-2-yl-urea. In addition, cleavage of the 
methanesulfonamidomethyl side chain leading to the free amine with 
further transformation to the alcohol (2-[3-(4,6-dimethoxypyrimidin-2-
yl)ureidosulfonyl]-4-methanesulfonamidomethyl-benzoic acid) was also 
seen. An additional minor metabolite was a benzoic acid metabolite, 
formed by hydrolysis of the methyl ester of the parent.
     Metabolism studies on mesosulfuron-methyl in ruminants and poultry 
were performed with application of dose levels which were equivalent to 
20 ppm and 10 ppm, respectively. The results showed that mesosulfuron-
methyl is predominantly excreted with little systemic distribution and 
limited metabolism. Residue levels in milk, meat and eggs were 
extremely low and the elimination from tissues was rapid. No tolerances 
have been proposed for animal tissues. The metabolic pathway in 
ruminants and poultry was similar to that in rats.
    7. Endocrine disruption. No special studies investigating potential 
estrogenic or endocrine effects of mesosulfuron-methyl have been 
conducted. However, the standard battery of required studies has been

[[Page 60382]]

completed. These studies 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. These 
studies are generally considered to be sufficient to detect any 
endocrine effects and no such effects were noted in any of the studies 
with mesosulfuron-methyl.

C. Aggregate Exposure

    1. Dietary exposure. Mesosulfuron-methyl is proposed for use as an 
herbicide on cereals. No non-agricultural uses are anticipated. The 
potential sources of exposure would consist of any potential residues 
in food and drinking water.
    i. Food. Chronic dietary analysis was conducted to estimate 
exposure to potential mesosulfuron-methyl residues in/on wheat. A Tier 
I analysis was conducted using the DEEMTM software and the 
1994-1996 Continuing Survey of Food Intake by Individuals (CSFII) food 
consumption data. It was assumed that residues were at tolerance levels 
of 0.03 ppm in grain and that 100% of crop was treated. Additionally, 
based on the results from appropriate studies, it was assumed that 
there was no concentration into processed commodities and that 
contributions from residues in meat, milk or eggs are not required. A 
chronic RfD of 1 mg/kg/day is derived from the 18-month mouse NOAEL of 
103 mg/kg bwt/day, applying an uncertainty factor of 100 to account for 
intra-species variation and inter-species extrapolation. Using these 
input parameters, chronic exposure estimates for the U.S. population 
and all 25 population subgroups utilized less than 0.01% of the chronic 
reference dose. The most highly exposed population subgroup was non-
nursing infants (<0.01% cRfD). These values are highly conservative, 
having been based on worst case assumptions of tolerance level residues 
and 100% of the crop treated.
    ii. Drinking water. EPA's standard operating procedure (SOP) for 
drinking water exposure and risk assessments was used to perform the 
drinking water assessment. This SOP uses a variety of tools to conduct 
a screening level drinking water assessment. These tools include water 
models such as Screening Concentration in Groundwater (SCI-GROW), 
Generic Expected Environmental Concentration (GENEEC), EPA's Pesticide 
Root Zone Model/Exposure Analysis Modeling System (PRZMS/EXAMS), the 
Food Quality Act (FQPA) Index Reservoir Screening Tool, and monitoring 
data. If monitoring data are not available, then models are used to 
predict potential residues in surface water and ground water and the 
highest value is assumed to be the potential drinking water residue. In 
the case of mesosulfuron-methyl, monitoring data do not exist; 
therefore, a Tier 1 model calculation was conducted to estimate a water 
residue. The calculated drinking water levels of comparison (DWLOC) for 
chronic exposures for adults is 35,000 ppb (35 ppm). The chronic DWLOC 
for children/toddlers is 15,000 ppb (15 ppm). The worst case chronic 
drinking water estimated concentration (DWEC) is 0.105 ppb based on the 
FQPA Index Reservoir Screening Tool simulation of runoff into surface 
water in a standard EPA exposure assessment scenario. The calculated 
DWLOCs for chronic exposures for all adults and children, therefore, 
greatly exceed the DWECs from the models.
    2. Non-dietary exposure. Exposure to mesosulfuron-methyl for the 
mixer/loader/ground boom/aerial applicator was calculated using the 
Pesticide Handlers Exposure Database (PHED). It was assumed that the 
product would be applied to a maximum of 32 hectares per day (80 A/day) 
by ground boom applicator and 140 hectares per day (350 A/day) by 
aerial applicator at a maximum use rate of 15 grams active ingredient/
hectares (a.i./ha.) Normal work attire consisting of long-sleeved 
shirt, long pants, and protective gloves was assumed in the PHED 
assessment. Margin of exposures (MOEs) for a 70 kg operator were 
calculated utilizing the NOAEL of 648 mg/kg body weight/day from the 
90-day dog dietary study, which is adjusted for a 15% dermal absorption 
as revealed in an in vivo dermal absorption study, and 100% inhalation 
absorption to obtain the absorbed dermal and inhalation dose, 
respectively. The combined MOE (inhalation plus dermal) for 
mesosulfuron-methyl was 3,240,000 for a ground operator undertaking 
mixing, loading and spraying. For aerial application where the mixer/
loader was assumed to be a different operator from the pilot, combined 
MOEs were 926,000 for the mixer/loader and 12,000,000 for the pilot. 
The results indicate that large margins of safety exist for the 
proposed use of mesosulfuron-methyl.

D. Cumulative Effects

     There is no available data at this time to determine whether 
mesosulfuron-methyl has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Therefore, a cumulative assessment was not done for this 
chemical.

E. Safety Determination

    1. U.S. population. Using the conservative assumptions described 
above, based on the completeness and reliability of the toxicity data, 
it is concluded that aggregate exposure, in this case food only, to the 
proposed uses of mesosulfuron-methyl will utilize <0.01% of the 
reference dose for the U.S. population. The actual exposure is likely 
to be much less as more realistic data and models are developed. EPA 
generally has no concern for exposures below 100% of the RfD because 
the RfD represents the level at or below which daily aggregate exposure 
over a lifetime will not pose appreciable risk to human health. 
Drinking water levels of comparison based on the dietary exposure are 
much greater than highly conservative estimated levels, and would be 
expected to be well below the 100% level of the RfD, if they occur at 
all. Therefore, there is a reasonable certainty that no harm will occur 
to the U.S. population from aggregate exposure (food and drinking 
water) to mesosulfuron-methyl.
    2. Infants and children. No evidence of increased sensitivity to 
fetuses was noted in developmental toxicity studies in rats or rabbits. 
There has been no indication of reproductive effects or indication of 
increased sensitivity to the offspring in the 2-generation rat 
reproduction study. No additional safety factor to protect infants and 
children is necessary as there is no evidence of increased sensitivity 
in infants and children.
     Using the conservative assumptions described in the exposure 
section above, the percent of the reference dose that will be used for 
exposure to residues of mesosulfuron-methyl in food for non-nursing 
infants (the most highly exposed sub group) is <0.01%. The children (1-
6) exposure uses are also <0.01% of the reference dose. As in the adult 
situation, drinking water levels of comparison are much higher than the 
worst case drinking water estimated concentrations and are expected to 
use well below 100% of the reference dose, if they occur at all. 
Therefore, there is a reasonable certainty that no harm will occur to 
infants and children from aggregate exposure to residues of 
mesosulfuron-methyl.

F. International Tolerances

     There are no Codex Alimentarius Commission maximum residue levels 
established for residues of mesosulfuron-methyl.
[FR Doc. 03-26670 Filed 10-21-03; 8:45 am]

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