[Federal Register Volume 63, Number 53 (Thursday, March 19, 1998)]
[Notices]
[Pages 13401-13404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-7141]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-797; FRL-5776-7]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various agricultural commodities.
DATES: Comments, identified by the docket control number PF-797, must
be received on or before April 20, 1998.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (7502C),
Office of Pesticides Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119,
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, Product
Manager (PM) 25, Registration Division, (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 239, 1921 Jefferson
Davis Hwy., Arlington, VA., (703) 305-5697; e-mail:
Tompkins.jim@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various raw
agricultural commodities under section 408 of the Federal Food, Drug,
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these
petitions contain data or information regarding the elements set forth
in section 408(d)(2); however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
supports grantinig of the petition. Additional data may be needed
before EPA rules on the petition.
The official record for this notice, as well as the public version,
has been established for this notice of filing under docket control
number PF-797 (including comments and data submitted electronically as
described below). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The
official record is located at the address in ``ADDRESSES'' at the
beginning of this document.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number PF-797 and appropriate petition
number. Electronic comments on this notice may be filed online at many
Federal Depository Libraries.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: March 3, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
E.I. du Pont de Nemours & Company, Agricultural Products
PP 3F4215
EPA has received a pesticide petition (PP 3F4215) from E.I. du Pont
de Nemours & Company, Agricultural Products, P.O. Box 80038,
Wilmington, DE 19880-0038, proposing pursuant to section 408(d) of the
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR
part 180 by establishing a tolerance for residues of metsulfuron methyl
(methyl-2-[[[[(4-methoxy-6-methyl-1-3, 5-triazin-2-yl)amino]carbonyl]
amino]sulfonyl]benzoate) in or on the raw agricultural commodities
sorghum grain at 0.1 parts per million (ppm), sorghum forage at 0.2
ppm, and sorghum fodder at 0.2 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
metsulfuron methyl is adequately understood. Metabolism studies
conducted with radioactive 14C-metsulfuron methyl on wheat and barley
under field conditions and on wheat under greenhouse conditions showed
that residues dissipate rapidly in plants, primarily due to growth
dilution. In these metabolism studies conducted at exaggerated rates,
wheat and barley grain did not contain any detectable level of
metsulfuron methyl or its metabolites (<0.01 mg/kg).="" residues="" of="" individual="" metabolites="" were="" very="" low="" in="" straw="" in="" studies="" conducted="" at="" 35="" g="" a.i./ha="" (0.5="" oz="" a.i./acre,=""><0.01 to="" 0.02="" mg/kg).="" the="" only="" situation="" where="" residues="" of="" an="" [[page="" 13402]]="" individual="" substance="" was="" detected="" in="" straw="" above="" 0.1="" mg/kg="" was="" under="" greenhouse="" conditions="" at="" 70="" g="" a.i./ha="" (1="" oz="" a.i./acre),="" (="" 8="" x="" maximum="" recommended="" rate),="" metsulfuron="" methyl="" residue="" level="" measured="" in="" straw="" at="" maturity="" was="" 0.44="" mg/kg="" (other="" individual="" metabolites="" were="" below="" 0.1="" mg/kg).="" the="" initial="" step="" of="" the="" metabolic="" breakdown="" of="" metsulfuron="" methyl="" involves="" either="" hydroxylation="" of="" the="" phenyl="" ring="" and="" subsequent="" conjugation="" with="" glucose="" or="" cleavage="" of="" the="" sulfonylurea="" bridge.="" the="" latter="" process="" results="" in="" triazine="" amine="" derivatives="" from="" one="" side="" of="" the="" molecule="" and="" sulfonamide="" derivatives="" from="" the="" other="" side,="" which="" may="" further="" evolve="" to="" saccharin="" through="" cyclization.="" plant/animal="" comparative="" metabolism="" showed="" two="" plant="" unique="" metabolites="" (4-hydroxy="" metsulfuron="" methyl="" and="" its="" glucose="" conjugate).="" however="" they="" do="" not="" occur="" at="" detectable="" levels="">< 0.01="" mg/kg)="" in="" cereal="" grain,="" even="" at="" exaggerated="" rates="" of="" application.="" for="" this="" reason="" they="" were="" not="" subject="" to="" any="" testing="" and="" were="" not="" of="" concern="" for="" the="" purpose="" of="" establishing="" the="" proposed="" tolerance.="" based="" on="" the="" absence="" of="" detectable="" residue="" in="" food="" commodities="" (wheat="" and="" barley="" grain)="" and="" on="" the="" expected="" low="" residue="" levels="" of="" individual="" substances="" in="" feed="" items="" (straw)="" under="" normal="" use="" conditions,="" and="" the="" residue="" chemistry="" guidelines="" (oppts="" 860-1300,="" d,="" ii)="" which="" states="" that;="" one="" metabolism="" study="" will="" be="" required="" for="" each="" of="" the="" crop="" groups="" defined="" in="" cfr="" 40="" 180.34(f)="" except="" for="" herbs="" and="" spices,="" a="" plant="" metabolism="" study="" in="" grain="" sorghum="" was="" not="" required.="" a="" confined="" crop="" rotation="" study="" was="" conducted="" using="" sugar="" beets,="" oats,="" rape="" and="" soybeans="" as="" following="" crops,="" an="" application="" rate="" of="" 16="" g="" a.i./ha,="" (0.23="" oz="" a.i./acre),="" (2="" x="" the="" maximum="" recommended="" rate)="" and="" a="" 120-day="" treatment-to-planting="" interval.="" a="" field="" crop="" rotation="" study="" was="" also="" conducted="" using="" oats,="" rape,="" sorghum="" and="" soybean="" as="" following="" crops,="" a="" 30="" g="" a.s./ha,="" (0.86="" oz="" a.i./acre),="" application="" rate="" and="" a="" 1-="" year="" treatment-to-planting="" interval.="" residues="" of="" metsulfuron="" methyl="" or="" its="" degradation="" products="" were="" not="" detected="" in="" any="" edible="" crop="" commodities=""><0.01 mg/kg),="" suggesting="" that="" use="" of="" metsulfuron="" methyl="" should="" not="" expose="" consumers="" to="" detectable="" residues="" in="" food="" through="" following="" crops.="" 2.="" analytical="" method.="" the="" quantification="" of="" metsulfuron="" methyl="" is="" by="" hplc/uv="" (high="" performance="" liquid="" chromatography/ultra="" violet)="" utilizing="" eluent="" and="" column="" switching="" with="" uv="" absorbance="" detection="" at="" 254="" nm.="" the="" loq="" (limits="" of="" quantitation)="" of="" the="" analytical="" method="" for="" sorghum="" is="" 0.10="" ppm="" for="" metsulfuron="" methyl="" and="" its="" metabolite="" (4-="" hydroxy="" metsulfuron="" methyl)="" in="" grain="" and="" fodder,="" 0.050="" ppm="" for="" metsulfuron="" methyl="" and="" its="" metabolite="" in="" forage,="" 0.070="" ppm="" for="" the="" glucose="" conjugate="" metabolite="" in="" grain="" and="" forage,="" and="" 0.14="" ppm="" for="" the="" glucose="" conjugate="" metabolite="" in="" fodder.="" the="" loq="" of="" the="" analytical="" method="" for="" metsulfuron="" methyl="" and="" its="" metabolite="" in="" wheat="" and="" barley="" is="" 0.05="" ppm="" for="" wheat/barley="" forage="" or="" grain="" and="" 0.10="" ppm="" for="" wheat/barley="" straw.="" 3.--a.="" magnitude="" of="" residues.="" the="" results="" of="" an="" analyses="" of="" sorghum="" grain,="" fodder="" and="" stover="" (at="" seed="" maturity),="" forage="" and="" hay="" (30="" days),="" after="" application="" of="" metsulfuron="" methyl="" at="" the="" maximum="" proposed="" label="" rate="" and="" twice="" the="" rate,="" show="" that="" all="" residues="" of="" metsulfuron="" methyl="" and="" its="" metabolites="" (4-hydroxy="" metsulfuron="" methyl="" and="" its="" glucose="" conjugate)="" were="" below="" the="" limit="" of="" quantitation="" (0.05="" or="" 0.1="" ppm).="" b.="" magnitude="" of="" residues="" in="" processed="" commodities.="" sorghum="" was="" field="" treated="" with="" metsulfuron="" methyl="" at="" exaggerated="" rates="" and="" samples="" were="" analyzed="" for="" metsulfuron="" methyl="" and="" its="" metabolites="" in="" bran,="" large="" grits,="" small="" grits,="" flour,="" grain="" dust,="" starch="" and="" gluten.="" all="" residues="" of="" metsulfuron="" methyl="" and="" it's="" metabolites="" in="" sorghum="" seeds="" and="" its="" processed="" fractions="" were="" below="" the="" limit="" of="" quantitation=""><0.02-0.05 ppm).="" b.="" toxicological="" profile="" 1.="" acute="" toxicity.="" based="" on="" epa="" criteria,="" technical="" metsulfuron="" methyl="" is="" in="" acute="" toxicity="" category="" iv="" for="" oral="" and="" inhalation="" routes="" of="" exposure="" and="" for="" dermal="" irritation="" and="" category="" iii="" for="" the="" dermal="" route="" of="" exposure="" and="" for="" eye="" irritation.="" it="" is="" not="" a="" skin="" sensitizer.="" acute="" oral="" toxicity="" in="" rats="" ld50="">5000 mg/kg
Acute dermal toxicity in rabbits LD50>2000 mg/kg
Acute inhalation toxicity in rats LD50>5.0 mg/L
Primary eye irritation in rabbits Effects reversed within 72
hours.
Primary dermal irritation in rabbits No irritation observed.
Dermal sensitization in guinea pigs Non-sensitizer.
2. Genotoxicty. Metsulfuron methyl has shown no genotoxic activity
in the following listed in-vitro and in-vivo tests, except for in-vitro
chromosomal aberration (CHO):
Ames Negative
Mammalian gene mutation (CHO/HGPRT) Negative
Unscheduled DNA synthesis Negative
In-vivo bone marrow cytogenetics Negative
In-vivo mouse micronucleus Negative
In-vitro chromosomal aberration (CHO) Positive
Metsulfuron methyl was only positive at concentrations > 1,000 mg/L
in an in vitro test for induction of chromosome aberrations in Chinese
Hamster Ovary cells. In vivo studies included the assessment of
chromosome aberrations by metaphase analysis in bone marrow of male and
female rats and the evaluation of micronuclei in bone marrow
polychromatic erythrocytes of male and female mice. The results of both
studies were negative when exposures were conducted up to 5,000 mg/kg.
The fact that no effects were observed in the more definitive in vivo
tests and considering the negative results in all other genotoxicity
studies, the weight-of-evidence indicates that metsulfuron methyl is
neither genotoxic nor mutagenic.
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 metsulfuron methyl. In a
rat multigeneration reproduction study, reduced parental body weights
were observed for both generations at the highest dose tested, 5,000
ppm. There were no effects on fertility, lactation, litter size or pup
survival. The NOEL was 500 ppm (or 34 to 43 mg/kg bw/day).
In studies conducted to evaluate developmental toxicity potential,
metsulfuron methyl was neither teratogenic nor uniquely toxic to the
conceptus (i.e., not considered a developmental toxin). In the rat
study, maternal toxicity, presented as reduced food consumption and
body weight gain, was observed at 250 mg/kg bw and above. The systemic
NOEL for the dams was 40 mg/kg/day. There were no effects on the
conceptus at the highest dose tested, 1,000 mg/kg/day. Therefore, the
fetal NOEL for rats is greater than 1000 mg/kg/day. In the rabbit
developmental toxicity study, maternal mortality, reduced food
consumption, and reduced body weights were observed at or above 100 mg/
kg bw. The NOEL for maternal toxicity in rabbits was 25 mg/kg, based on
maternal mortality and body weight decreases. Impact on the fetuses was
minimum at these maternally toxic doses and was characterized only by a
non-statistically significant trend in incomplete ossification of
frontal bones at 100 and 300 mg/kg bw and above. The NOEL for fetal
toxicity in rabbits was >700 mg/kg, the highest dose tested.
[[Page 13403]]
4. Subchronic toxicity. Repeated dietary exposures to metsulfuron
methyl presented low toxicity manifested as reduced food consumption
and body weight gain in the rat and the dog. There were no adverse
effects observed in mice in subchronic studies at the highest dose
tested, 5,000 ppm. The NOEL for subchronic exposure in mice was >5000
ppm (814 and 944 mg/kg/day, M/F). The rat was the most sensitive
species tested in subchronic toxicity studies. The NOEL was 1,000 ppm
(68 and 84 mg/kg/day for males amd females respectively) based on
decreased body weights, body weight gains, and total serum protein in
females, and decreased relative liver weights in males exposed at 7,500
ppm. In a 90-day feeding study in dogs, the NOEL was 5,000 ppm (134 and
129 mg/kg/day, M/F), the highest dose tested.
A 21-day dermal study was conducted in rabbits at 0, 125, 500 or
2,000 mg/kg/day. The NOEL was 125 mg/kg/day based on dermal effects at
the application site; the NOEL for systemic toxicity was 2,000 mg/kg/
day.
5. Chronic toxicity. Chronic Toxicity studies of metsulfuron methyl
resulted in only minimal effects in the rat, mouse, or dog. Metsulfuron
methyl was not oncogenic in the chronic rat and mouse bioassays.
A 1-year feeding study in dogs, the NOEL for chronic toxicity in
beagle dogs was 500 ppm (or 13 mg/kg/day) and 5,000 ppm (or 127 mg/kg/
day) in male and female dogs, respectively. Metsulfuron methyl produced
minimal toxicity after 12 months administration to male beagle dogs,
manifested as minimal interference with normal nutrition by decreasing
food consumption toward the end of 1 year. This minimal interference
was not considered adverse since it did not cause changes in body
weights or body weight gains.
In an 18-month study in mice, the NOEL was 5,000 ppm (666 and 836
mg/kg/day for males and females, respectively), the highest dose
tested. Metsulfuron methyl is not an oncogen in this study.
A 2-year combined chronic toxicity and oncogenicity study in rats,
the NOEL was 500 ppm (or 23 and 30 mg/kg/day for males and females,
respectively). Metsulfuron methyl was not oncogenic in rats nor was
target organ toxicity evident after two years administration. Chronic
toxicity was manifested as minimal interference with normal nutrition
and subsequent decreases in body weight gain that were more pronounced
during the early growth phase of the animals life span and became less
evident toward the end of the study.
6. Animal metabolism. The metabolism of metsulfuron methyl in
animals (rat, hen and goat) is adequately understood and similar among
the species evaluated. The rat metabolism and disposition data
indicated rapid absorption, metabolism and elimination. In the rat,
approximately 90% of the administered dose of metsulfuron methyl was
excreted in the feces and urine within 72 hours. The biological half-
lives were 9-16 hours for low-dose groups and 23-29 hours for high-dose
groups. The major pathway was breakdown of the urea bridge to give rise
to either aminosulfonyl benzoate or sulfonamide and the triazine amine
derivative. The secondary biotransformation pathway was demethylation
of aminosulfonyl benzoate to form saccharin. Preconditioning with low-
dose exposures did not affect the metabolism of metsulfuron methyl.
There was no evidence of accumulation of metsulfuron methyl or its
metabolites in any organ or tissue. A significant portion (85-95%) of
the recovered radioactivity from urine, feces and tissues was intact
metsulfuron methyl. There were two major plant specific metabolites
identified, that were not detected in the rat. However, in residue
studies, no detectable residues of parent or major plant unique
metabolites, were found in the feed and food items of cereal crops
treated at the maximum seasonal use rate. Hence, toxicity testing of
other degradation products of metsulfuron methyl was not needed.
Results from a metabolism study with two radioactive forms of
metsulfuron methyl, (14C-Phenyl and 14C-Triazine) in the laying hens
show that virtually all the radioactivity was eliminated in the
excreta. The total radioactivity in edibale tissues and eggs
represented <10% of="" the="" metsulfuron="" methyl="" residue="" level="" was="" found="" as="" the="" glucoronide="" conjugate.="" residues=""><0.1 ppm)="" were="" found="" in="" the="" kidney="" of="" cows="" slaughtered="" 12="" hours="" after="" treatment="" stopped="" but="" not="" in="" cows="" slaughtered="" a="" week="" later.="" tolerances="" for="" metsulfuron="" methyl="" in="" fat="" (0.1="" ppm),="" meat="" (0.1="" ppm),="" meat="" by="" products="" (0.1="" ppm),="" and="" kidney="" (0.5="" ppm)="" of="" cattle,="" goats,="" hogs,="" horses="" and="" sheep,="" and="" a="" tolerance="" of="" 0.05="" ppm="" in="" milk="" have="" been="" posted="" in="" 40cfr="" 180.428.="" 7.="" metabolite="" toxicology.="" there="" is="" no="" evidence="" that="" the="" metabolites="" of="" metsulfuron="" 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="" metsulfuron="" 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="" metsulfuron="" methyl="" has="" an="" adverse="" effect="" on="" the="" endocrine="" system.="" c.="" aggregate="" exposure="" 1.="" dietary="" exposure.="" tolerances="" have="" been="" established="" (40="" cfr="" 180.428)="" for="" the="" residues="" of="" metsulfuron="" methyl="" in="" or="" on="" various="" food="" commodities="" ranging="" from="" 0.05="" ppm="" in="" milk="" to="" 0.5="" in="" kidney.="" there="" are="" no="" potential="" sources="" of="" exposure="" of="" the="" general="" population="" to="" residues="" of="" metsulfuron="" methyl="" from="" drinking="" water="" or="" non-occupational="" sources="" such="" as="" in="" door="" and="" out="" door="" residential="" uses.="" there="" are="" no="" in="" door="" or="" out="" door="" residential="" uses="" registered="" for="" metsulfuron="" methyl.="" there="" are="" no="" acute="" dietary="" exposure="" or="" cancer="" risk="" endpoints="" of="" concern="" for="" metsulfuron="" methyl.="" aggregate="" risk="" has="" been="" assessed="" from="" chronic="" exposure="" to="" food.="" 2.="" food.="" tolerances="" have="" been="" established="" for="" metsulfuron="" methyl="" on="" the="" following="" food="" crops:="" barley,="" wheat,="" and="" sugar="" cane.="" a="" tolerance="" of="" 0.1="" ppm="" for="" sorghum="" grain="" was="" included="" in="" this="" assessment.="" also="" included="" were="" tolerances="" for="" meat="" and="" milk="" commodities.="" the="" dietary="" exposure="" was="" estimated="" using="" the="" dietary="" exposure="" evaluation="" model="" (deem="" ver.="" 5.03)="" which="" utilizes="" the="" 1989-1991="" csfii="" food="" consumption="" database.="" in="" conducting="" this="" assessment="" the="" [[page="" 13404]]="" conservative="" assumption="" was="" made="" that="" residues="" would="" be="" at="" the="" tolerance="" level.="" use="" of="" the="" tolerances="" rather="" than="" actual="" field="" measurements="" will="" result="" in="" an="" overestimate="" of="" human="" dietary="" exposure.="" the="" existing="" metsulfuron="" methyl="" tolerances="" with="" the="" addition="" of="" the="" sorghum="" tolerance="" result="" in="" a="" theoretical="" maximum="" residue="" level="" (tmrc)="" that="" is="" equivalent="" to="" the="" following="" percentages="" of="" the="" rfd:="" u.s.="" population="" 0.3%="" nursing="" infants=""><1 year="" old)="" 0.1%="" non-nursing="" infants=""><1 year="" old)="" 0.4%="" children="" (1-6="" years="" old)="" 0.8%="" children="" (7-12="" years="" old)="" 0.5%="" thus,="" the="" estimated="" exposure="" for="" the="" u.s.="" population="" and="" all="" subpopulation="" was="" less="" than="" 1%="" of="" the="" rfd.="" metsulfuron="" methyl="" rfd="" (0.3="" mg/kg/day)is="" based="" on="" the="" noel="" for="" the="" 2-year="" rat="" study.="" the="" most="" sensitive="" chronic="" toxicity/oncogenicity="" study.="" the="" subpopulation="" with="" the="" highest="" exposure="" was="" children="" ages="" 1-6="" years="" (0.8%="" of="" the="" rfd).="" based="" on="" the="" residue="" data,="" potential="" for="" dietary="" exposure="" is="" extremely="" low.="" residue="" studies="" have="" shown="" no="" residue="" above="" loq="" (0.05="" or="" 0.02="" ppm)="" in="" sorghum="" samples="" evaluated="" including="" the="" sorghum="" grain="" processed="" fractions.="" no="" dietary="" exposure="" is="" anticipated="" from="" secondary="" residues="" in="" meat="" or="" milk.="" although="" sorghum="" is="" considered="" a="" major="" foodstuff="" for="" cattle="" and="" poultry,="" residue="" studies="" and="" metabolism="" studies="" in="" the="" laying="" hen="" and="" lactating="" goat="" and="" cattle="" feeding="" studies="" showed="" residues="" below="" loq="" of="" processed="" fractions="" and="" less="" than="" 2%="" of="" the="" administered="" concentration="" in="" edible="" meat="" and="" eggs.="" only="" traces="" of="" metsulfuron="" methyl="" were="" found="" in="" some="" goat="" meat="" and="" milk="" (0.008-0.009).="" direct="" human="" consumption="" of="" sorghum="" grain="" as="" a="" food="" commodity="" in="" the="" u.s.="" is="" extremely="" low.="" at="" the="" above="" levels="" of="" exposure,="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" dietary="" exposure="" to="" metsulfuron="" methyl.="" 3.="" drinking="" water.="" another="" potential="" source="" of="" dietary="" exposure="" to="" pesticides="" are="" residues="" in="" drinking="" water.="" there="" is="" no="" established="" maximum="" contaminant="" level="" (mcl)="" for="" metsulfuron="" methyl="" in="" water.="" based="" on="" the="" low="" use="" rate="" of="" metsulfuron="" methyl="" and="" a="" use="" pattern="" that="" is="" not="" widespread,="" dupont="" does="" not="" anticipate="" residues="" of="" metsulfuron="" methyl="" in="" drinking="" water="" and="" exposure="" from="" this="" route="" is="" unlikely.="" 4.="" non-dietary="" exposure.="" metsulfuron="" methyl="" is="" registered="" for="" use="" in="" weed="" and="" brush="" control="" in="" non-crop="" situations="" including="" industrial,="" unimproved="" turf="" areas.="" metsulfuron="" methyl="" is="" not="" to="" be="" used="" on="" lawns,="" walks,="" drive="" ways,="" tennis="" courts,="" golf="" courses,="" athletic="" fields,="" commercial="" sod="" operations,="" or="" other="" high="" maintenance,="" fine="" turf="" grass="" areas,="" or="" similar="" areas.="" any="" non-occupational="" exposure="" to="" metsulfuron="" methyl="" in="" the="" unimproved="" areas="" is="" likely="" to="" be="" negligible.="" d.="" cumulative="" effects="" metsulfuron="" methyl="" belongs="" to="" the="" sulfonylurea="" class="" of="" compounds.="" the="" herbicidal="" activity="" of="" the="" sulfonylurea="" is="" due="" to="" the="" inhibition="" of="" acetolactase="" synthase="" (als),="" an="" enzyme="" only="" found="" in="" plants.="" als="" is="" part="" of="" the="" biosynthetic="" pathway="" leading="" to="" the="" formation="" of="" branched="" chain="" amino="" acids.="" animals="" lack="" als="" and="" this="" biosynthetic="" pathway.="" this="" lack="" of="" als="" contributes="" to="" the="" low="" toxicity="" of="" the="" sulfonylurea="" compounds="" in="" animals.="" we="" are="" aware="" of="" no="" information="" to="" indicate="" or="" suggest="" that="" metsulfuron="" methyl="" has="" any="" toxic="" effects="" on="" mammals="" that="" would="" be="" cumulative="" with="" those="" of="" any="" other="" chemicals.="" e.="" safety="" determination="" 1.="" u.s.="" population.="" using="" the="" conservative="" exposure="" assumptions="" described="" above,="" and="" based="" on="" the="" most="" sensitive="" chronic="" noel="" of="" 25="" mg/="" kg/day="" and="" an="" rfd="" of="" 0.3="" mg/kg/day,="" the="" aggregate="" dietary="" exposure="" will="" utilize="" less="" than="" 1%="" of="" the="" rfd="" for="" the="" u.s.="" population.="" generally,="" exposure="" below="" 100%="" of="" the="" rfd="" are="" of="" no="" concern="" because="" the="" rfd="" represents="" the="" level="" at="" or="" below="" which="" daily="" aggregate="" dietary="" exposure="" over="" a="" lifetime="" will="" not="" pose="" risk="" to="" human="" health.="" we="" therefore="" conclude="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" aggregate="" exposure="" to="" metsulfuron="" methyl="" residues.="" although="" no="" formal="" acute="" dietary="" margin="" of="" exposure="" (moe)="" determinations="" were="" made,="" it="" is="" highly="" unlikely="" that="" the="" moe="" would="" exceed="" a="" level="" of="" concern="" due="" to="" the="" low="" acute="" mammalian="" toxicity="" of="" this="" compound].="" 2.="" infants="" and="" children.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" metsulfuron="" methyl,="" data="" were="" considered="" from="" developmental="" toxicity="" studies="" in="" the="" rat="" and="" the="" rabbit,="" and="" a="" multi-generation="" reproduction="" study="" in="" the="" rats.="" these="" studies="" proved="" that="" metsulfuron="" methyl="" was="" not="" a="" teratogenic="" or="" a="" developmental="" toxin.="" using="" the="" conservative="" exposure="" assessment="" described="" above,="" the="" percent="" of="" the="" rfd="" that="" will="" be="" utilized="" ranges="" from="" 0.1="" to="" 0.8%="" for="" infants="" and="" young="" children.="" based="" on="" this="" we="" conclude="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" metsulfuron="" methyl="" residues.="" although="" no="" formal="" acute="" dietary="" margin="" of="" exposure="" determinations="" were="" made,="" it="" is="" highly="" unlikely="" that="" the="" moe="" would="" exceed="" a="" level="" of="" concern="" due="" to="" the="" low="" mammalian="" toxicity="" of="" this="" compound.="" f.="" international="" tolerances="" there="" are="" no="" canadian,="" mexican,="" or="" codex="" maximum="" residue="" level="" (mrls)="" for="" metsulfuron="" methyl="" on="" sorghum="" grain.="" [fr="" doc.="" 98-7141="" filed="" 3-18-98;="" 8:45="" am]="" billing="" code="" 6560-50-f="">