**EPA Registration Division Contact :** Mr. J. A. Tompkins, 703-305-5697

1\. E.I. du Pont de Nemours and Company

PP Nos. (to be assigned)

EPA has received pesticide petitions (PP Nos. to be assigned) from E.I.
du Pont de Nemours and Company, Crop Protection Products, Laurel Run
Plaza, P.O. Box 80038, Wilmington, DE 19880-0038, and the Interregional
Research Project No. 4 (IR-4), 681 U.S. Highway #1 South, North
Brunswick, New Jersey 08902-3390, 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 180.451 by establishing a tolerance for residues of
the herbicide, tribenuron methyl (methyl
2-\[\[\[\[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)methylamino\]carbonyl\]amino\]sulfonyl\]
benzoate) in or on the following raw agricultural commodities:
Sunflowers at 0.05 ppm; Rice grain and straw at 0.05 ppm; Field corn
forage, stover, and grain at 0.05 ppm; Grain sorghum forage, stover, and
grain at 0.05 ppm; and Soybean seed at 0.05 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 tribenuron methyl is
adequately understood.

Tribenuron methyl is rapidly metabolized in wheat plants with a
half-life of less than 4 days. A major metabolic reaction was
N-demethylation of tribenuron methyl to form metsulfuron methyl.
Metsulfuron methyl was further metabolized, primarily through rapid
hydroxylation of the phenyl ring, followed by conjugation with glucose.
Hydrolysis of the sulfonylurea bridge of tribenuron methyl to release
sulfonamide and triazine amine was also observed. The sulfonamide may be
further metabolized to hydroxylated sulfonamide or cyclized to
saccharin. The presence of alpha-hydroxy triazine amine, N-demethyl
triazine amine, and O-demethyl N-demethyl triazine amine demonstrated
that the released triazine moiety of tribenuron methyl was also
extensively degraded in wheat. Metabolism studies were conducted with
radioactive \[^14^C\]-tribenuron methyl on wheat under field conditions.
Wheat plants at the tillering stage were treated with 72-75 g active
ingredient (ai)/ha of \[^14^C\]-phenyl and \[^14^C\]-triazine labeled
tribenuron methyl. Samples were harvested 0, 4, 8, 14, 21, 28, and 63
days after treatment. Total \[^14^C\] residue levels in the foliage
declined rapidly from 5.5 ppm at time of application to 0.55 ppm in the
mature straw and 0.05 ppm in the grain (\[^14^C\]-phenyl), and from 4.2
ppm to 0.37 ppm in the mature straw and 0.01 ppm in the grain
(\[^14^C\]-triazine). Analysis of the wheat foliage and straw extracts
by HPLC and TLC revealed that tribenuron methyl was rapidly and
extensively metabolized. Metabolites were identified based on
chromatography with authentic standards. The major metabolites were the
glucose conjugate of hydroxylated metsulfuron methyl, hydroxylated
saccharin, the glucose conjugate of hydroxylated saccharin, saccharin,
triazine amine, O-demethyl triazine amine, and O-hydroxy triazine amine.

A metabolism study was conducted with \[^14^C\] Tribenuron methyl on
ALS-Tolerant Canola. \[^14^C\] Tribenuron methyl was applied at 25 g
ai/ha as a topical spray treatment at the 2 true leaf stage to bolting.
Whole canola plants were harvested at 0, 2, and 35 days after treatment,
and at maturity (78 days after treatment). Total reactive residue (TRR)
in canola foliage, when expressed as tribenuron methyl equivalents,
declined from, on average, 0.26 ppm at day 0 to 0.04 ppm at day 35. TRR
in immature 35-day canola seed pods was not higher than 0.04 ppm, and
was 0.02 ppm in 78-day seed samples. \[^14^C\] Tribenuron methyl
accounted for greater than 81% of the radioactive residue in the 0 and 2
day foliage samples. Other minor components were polar metabolites or
conjugates, each less than 10% of the TRR. No single component in the
polar metabolites exceeded 0.01 ppm. In the 35-day foliage samples,
\[^14^C\] tribenuron methyl accounted for only about 11-25.5% of the
TRR, which is less than 0.01 ppm. The average half life for \[^14^C\]
tribenuron methyl was 15 days. Several metabolic processes in the
foliage are involved. They include a hydrolytic cleavage of tribenuron
methyl as well as N-demethylation of tribenuron methyl. Other
demethylation and hydroxylation processes continued up to final harvest.
The results of the study suggest that the tribenuron methyl metabolic
process in canola follows a typical plant metabolism pattern, and no
accumulation of tribenuron methyl is anticipated in canola when it is
used in accordance with the proposed labels.

A metabolism study was conducted to determine the nature and magnitude
of the residues of tribenuron methyl in cotton plants after exposure to
\[2-^14^C\] tribenuron methyl. Soil treatments were applied at 0.3 oz
ai/acre as a direct spray in an aqueous suspension containing inert
dry-flowable formulation ingredients. The application was made
immediately after planting cotton to provide the data for the shortest
anticipated time between application and planting. No terminal residues
at or above 0.01 ppm were observed in any triazine-label treated
fractions of mature cotton after treatment with tribenuron methyl. No
detectable residues were found in the undelinted seed, and very low
residues (0.028 ppm) were observed in the gin trash after treatment.
Tribenuron methyl and its known metabolites are not expected to be
present in the terminal residues in gin trash or undelinted seed, when
applied according to the proposed label.

A confined crop rotation study with \[^14^C\]-phenyl tribenuron methyl
was conducted using red beets, cabbage, sorghum, soybeans and wheat
planted in pots of sandy loam soil 30 and 120 days after a single
application of \[^14^C\]-phenyl-labeled tribenuron methyl. For the
30-day aging period, samples from both treated and control crops were
taken at 28, 49, and 67 days after planting with additional samples
taken from the sorghum and soybeans plantings at 90 and 115 days. At
maturity, all remaining plants were harvested and subdivided into edible
and nonedible portions. Harvest dates, expressed as days after planting,
were: 90 days (cabbage), 115 days (beets and wheat), and 168 days
(sorghum and soybeans). Samples from all crops from the 120-day aging
study were taken at 28, 48, 69, and 90 days (maturity for wheat, beets
and cabbage) and 120 days and 169 days (maturity for sorghum and
soybeans). Tribenuron methyl dissipated rapidly in the soil with none of
the intact material detected after the 30-day aging period. The major
radiolabeled residue extracted from the soil was saccharin, which
remained in the soil at very low levels throughout the study. Some
accumulation of total radioactive residues was apparent in the mature
wheat, soybean, and sorghum foliage due to the dehydrated nature of
samples harvested. The major residue in the plants was identified as
saccharin.

A confined crop rotation study with \[^14^C\]-triazine tribenuron methyl
was conducted using sorghum, red beets, and cabbage. Sandy loam soil was
treated at 32 g ai/ha with \[^14^C\]-phenyl tribenuron methyl in the
greenhouse. Rotational crops were sown 30 and 120 days post-treatment.
Tribenuron methyl degraded rapidly in the soil with no detectable intact
material present 30 days post-treatment. The major radiolabeled
metabolite was the triazine amine. No significant accumulation (i.e.,
less than 0.01 ppm) of radiolabeled materials from the soil were
observed in the mature crops of cabbage foliage. Some accumulation of
the radioactivity was observed in the mature beet foliage in the 30-day
study (0.029 ppm) and the 120-day study (0.011 ppm). Major metabolites
were N-demethyl triazine amine and O-hydroxy triazine amine.
Accumulation of radioactivity was observed in the mature sorghum straw
due to the dehydrated nature of this plant tissue at harvest. Levels of
radiolabeled materials detected were 0.108 and 0.057 ppm in the 30-day
and 120-day studies, respectively. The major metabolites were highly
polar materials. Tribenuron methyl rapidly decomposes in soil to the
triazine amine, which is then degraded, not accumulated, in plants.

Based on the absence of quantifiable residues in food commodities
(barley and oat grain), and on the expected low residue levels of
individual substances in feed items (straw) under normal conditions, and
the Residue Chemistry Guidelines (OPPTS 860-1300, D, ii) which state
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 barley and oat was not required. Additionally, based
on the results of three metabolism studies on dissimilar crops (wheat,
canola and cotton) having similar metabolic routes, additional
metabolism studies for sunflowers, rice, field corn, soybeans, and grain
sorghum are not required.

2\. Analytical Methods

Various analytical methods are available for the determination of
residues of tribenuron methyl in barley grain, wheat grain, wheat straw,
and wheat forage samples. One method uses normal phase liquid
chromatography and a photoconductivity detector; and is based on
extraction of tribenuron methyl from crops with acetonitrile, and
cleanup on a silica cartridge. Recoveries for grain, straw and green
forage samples fortified between 0.01 and 0.10 ppm averaged 88% with a
standard deviation of 14%. The lower level of quantitation for grain and
green forage is 0.01 ppm and for straw 0.02 ppm. This method was updated
to a HPLC method with UV detection. The method provides a means to
quantitate tribenuron methyl in these matrices at levels as low as 0.05
ppm, based on a 5-gram sample, using column and eluent switching. More
recently, this method was further updated and provides for analysis of
wheat grain, straw, and forage by HPLC column switching and UV
detection. The limit of quantitation (LOQ) for this updated method is
0.01 ppm for wheat grain and wheat forage, and 0.05 ppm for wheat hay.

The analyses of sunflower samples were conducted with this further
updated method. The LOQ for the analysis of sunflower seed was 0.05 ppm
based on a 5-gram sample. This method was validated at 0.05 and 0.5 ppm,
with an average recovery of 70 % (+/- 6%) and 70% (+/- 3%),
respectively.

Methods have been developed for the analysis of Tribenuron methyl in
other crops. Residues of tribenuron methyl at levels of 0.02 ppm or
above in grass seed, straw, and seed screenings are quantified using gel
permeation chromatography and solid-phase extraction. Purified column
eluent is taken to dryness, dissolved in ethyl acetate, and analyzed by
capillary gas chromatography using a mass spectral detector. In
fortification recovery trials, an average recovery of 87.6 % with a
standard deviation of 21 % was obtained for eighteen grass seed samples
over a fortification range of 0.02 to 0.06 ppm. Tribenuron 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 UV detection at 258 nm, at levels as low as 0.02 ppm
(limit of quantitation) using a 5 gram sample. Residues in cotton seed
and cotton 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 0.02 ppm and the limit of detection was estimated to be 0.006 ppm,
based on a 5 gram sample.

Residues in rice grain and straw, corn forage and stover, and grain
sorghum forage and stover were determined with an analytical method
utilizing sample extraction by homogenization in a potassium phosphate
buffer solution. The extracts were cleaned-up and concentrated by
solid-phase extraction. Analysis was performed by reversed-phase HPLC
and quantitatively analyzed by tandem mass spectrometric detection. The
target limit of quantitation (LOQ) was 0.05 ppm in these commodities.

Thifensulfuron methyl residues in field corn grain, grain sorghum grain,
and soybean seed were determined by an analytical method utilizing
LC/MS/MS analysis. The analytes were resolved by HPLC chromatography and
quantitatively analyzed by tandem mass spectrometric detection. The LOQ
was 0.05 ppm in these commodities.

3\. Magnitude of Residue

a\. Wheat and Barley, Grain and Straw

A study was conducted to determine the extent of residues of tribenuron
methyl in wheat when applied at the maximum use rate (0.25 oz ai/A) 40
days before maturity. Samples of mature wheat grain and straw were taken
from treated and control plots at preharvest intervals ranging from 25
to 40 days after the test substance was applied. A two-step HPLC method
was used to determine tribenuron methyl at levels as low as 0.0075 ppm
in wheat grain based on a 20 gram sample, and 0.014 ppm in wheat straw
based on a 10 gram sample. No grain or straw samples showed quantifiable
residues of tribenuron methyl.

A study was conducted to determine the extent of residues of tribenuron
methyl in barley when applied at the maximum use rate (0.25 oz ai/A) 40
days before maturity. Samples of mature barley grain and straw were
taken from each plot at preharvest intervals ranging from 24 to 43 days
after the test substance was applied. A two-step HPLC method was used to
determine tribenuron methyl at levels as low as 0.0066 ppm in barley
grain based on a 20 gram sample, and 0.013 ppm in barley straw based on
a 10 gram sample. One of the grain samples showed a detectable residue
(0.0064 ppm) of tribenuron methyl, which is below the established grain
tolerance of 0.05 ppm. A straw sample from one of the sites contained
tribenuron methyl at 0.034 ppm, which is below the established straw
tolerance of 0.10 ppm. The remaining grain and straw samples showed no
detectable or quantifiable residues of tribenuron methyl.

The results of the analyses of grain and straw from wheat and barley
show that no residues were found in either grain or straw from plants
treated at or below the maximum recommended application rate of 0.25 oz.
ai/acre, with a 0.02 - 0.05 ppm LOQ. The preharvest intervals ranged
from 42-140 days. A small percentage of plants treated at higher rates
showed some residues in straw.

b\. Grass, Forage and Hay

Established plots of bluegrass, tall fescue, and perennial ryegrass
grown for production of grass seed were each treated with 0.25 oz ai/A
and 0.50 oz ai/A of tribenuron methyl. Sampling preharvest intervals
ranged from 56 to 85 days. Reliable detected residues of tribenuron
methyl (0.016 ppm or above) were not found in any crop fraction from any
test site, with one exception for a screenings waste sample with a
residue level of 0.004 ppm for the 0.25 oz ai/A treatment, and 0.006 ppm
for the 0.50 oz ai/A treatment. An attempt to reconfirm this result by
reextracting a second screening waste sample failed to confirm the
presence of these tribenuron methyl residues.

c\. Oat, Grain and Straw

A study was conducted to determine the extent of residues of tribenuron
methyl in oats when applied at one and two times the maximum use rate,
approximately 40 days before harvest. Samples of mature oat grain and
straw were taken from both treated and control plots at preharvest
intervals ranging from 39 to 57 days after the application of the test
substance. A two-step HPLC method was used to detect tribenuron methyl
residues in oat grain at levels as low as 0.0055 ppm based on a 20 gram
sample, and in oat straw at levels as low as 0.018 ppm based on a 10
gram sample. Residues of tribenuron methyl in oat grain from oats
treated at 1x and 2x rates were below the LOQ of 0.013 ppm and 0.01 ppm,
respectively. The residues of tribenuron methyl in oat straw were below
the LOQ of 0.018 ppm and 0.04 ppm, respectively - and also below
reported detection level of 0.009 ppm and 0.018 ppm, respectively, in
oat straw from oats treated at 1x and 2x rates.

d\. Canola and Flax

Magnitude of residue studies were conducted on seed fractions of canola
varieties containing the Smart™ trait. CDC Triffid flax was also
treated. The post-emergent broadcast application of tribenuron methyl at
0.07 and 0.14 oz. ai/acre represents one to two times the proposed use
rate on these canola and flax varieties. No tribenuron methyl residues
were found above the LOQ of 0.02 ppm in any seed samples treated with
the test substance at a use rate of 0.7 to 0.14 oz of tribenuron
methyl/acre.

e\. Cotton Seed and Gin Trash

Magnitude of residue studies were also conducted to determine residues
of tribenuron methyl in cotton seed and cotton gin trash. The study
consisted of three treatments. Treatment 1: One broadcast application at
0.15 oz ai/A, applied approximately 14 days prior to planting. Treatment
2: One broadcast application at 0.15 oz ai/A, applied pre-plant, on the
day of planting. Treatment 3: One broadcast application at 0.75 oz ai/A,
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 to 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 tribenuron 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.

f\. Sunflowers

Magnitude of the residue studies were conducted by IR-4 to determine
residues of tribenuron methyl in sunflowers. Test plots were treated
with three broadcast applications of tribenuron methyl, applied at rates
of 0.25 -- 1.3 oz ai/acre per application, for a total application rate
of 0.75 to 3.9 oz ai/acre per crop season. Commercially mature sunflower
seed samples were collected 67-84 days following the last application.
The results from these trials show that maximum residues of tribenuron
methyl are less than 0.05 ppm, which is the limit of quantitation.
Sunflowers treated with the 5X exaggerated rate of tribenuron methyl,
i.e., three applications at 1.3 oz ai/acre/application, also showed no
residues of tribenuron methyl at or above the LOQ. A sunflower
processing study was, therefore, not conducted.

g\. Corn Grain, Forage and Stover

Studies were conducted to determine residues of tribenuron methyl in
field corn grain, forage, and stover. Two test plots were established at
each site. One plot was untreated and provided control samples for
analysis. The other plot received one pre-planting or at-planting
application of tribenuron methyl at a rate of 1.25 oz ai/acre, which was
five times the maximum expected label rate. Field corn commodity samples
-- grain, forage, and stover - were collected at normal harvest (112-150
days after application, 75-106 days after application, and 112-150 days
after application, respectively) and analyzed for residues of tribenuron
methyl. In these exaggerated rate studies, at normal harvest, no
residues were detected (limit of detection 0.02 ppm) in any untreated
control or treated samples analyzed.

h\. Soybeans

Studies were conducted to determine residues of tribenuron methyl in
soybean seed. Two test plots were established at each site. One plot was
untreated and provided control samples for analysis. The other plot
received one pre-planting or at-planting application of tribenuron
methyl at a rate of 1.25 oz ai/acre, which was five times the maximum
expected label rate. Soybean seed samples were collected at normal
harvest (135-148 days after application) and analyzed for residues of
tribenuron methyl. In these studies, at normal harvest, no residues were
detected (limit of detection 0.02 ppm) in any untreated control or
treated samples analyzed.

i\. Rice Grain and Straw

Studies were conducted to determine residues of tribenuron methyl in
rice grain and straw. Two test plots were established at each site. One
plot was untreated and provided control samples for analysis. The other
plot received one pre-planting or at-planting application of tribenuron
methyl at a rate of 1.25 oz ai/acre, which was five times the maximum
expected label rate. Rice grain and straw samples were collected at
normal harvest (106-129 days after application) and analyzed for
residues of tribenuron methyl. In these exaggerated rate studies, at
normal harvest, no residues were detected (limit of detection 0.02 ppm)
in any untreated control or treated samples analyzed.

h\. Grain Sorghum Forage, Stover and Grain

Studies were conducted to determine residues of tribenuron methyl in
sorghum forage, stover, and grain. Two test plots were established at
each site. One plot was untreated and provided control samples for
analysis. The other plot received one pre-planting or at-planting
application of tribenuron methyl at a rate of 1.25 oz ai/acre, which was
five times the maximum expected label rate. Grain sorghum forage,
stover, and grain samples were collected at normal harvest (87-103 days
after application for forage, and 133-144 days after application for
stover and grain) and analyzed for residues of tribenuron methyl. In
these exaggerated rate studies, at normal harvest, no residues were
detected (limit of detection 0.02 ppm) in any untreated control or
treated samples analyzed.

B. Toxicological Profile

1\. Acute Toxicity

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

Acute oral toxicity in rats LD~50~ \> 5000 mg/kg

Acute dermal toxicity in rabbits LD~50~ \> 2000 mg/kg

Acute inhalation toxicity in rats LC~50~ \> 6.7 mg/L

Primary eye irritation in rabbits Moderate effects reversed within 3
days

Primary dermal irritation in rabbits Non-irritating

Dermal sensitization Sensitizer

2\. Genotoxicity

Technical tribenuron 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 CHO/HPRT Assay Negative

*In vitro* Unscheduled DNA Synthesis Negative

*In vivo* Cytogenetic Negative

*In vivo* Bone Marrow Metaphase Analysis (Rat) Negative

*In vivo* Micronuclei Induction (Mouse) Negative

Tribenuron methyl was negative for mutagenicity in an *in vitro*
bacterial gene mutation assay using *Salmonella* *typhimurium* and in an
*in vitro* mammalian cell gene mutation assay using Chinese hamster
ovary cells. In cultured primary rat hepatocytes *in vitro*, tribenuron
methyl was negative for the induction of unscheduled DNA synthesis.

In a test measuring clastogenic damage *in vivo*, tribenuron methyl was
negative for the induction of chromosome aberrations in male and female
rat bone marrow cells at 5000 mg/kg. A study measuring chromosome damage
*in vivo* was conducted. The study included the evaluation of
micronuclei in bone marrow polychromatic erythrocytes of male and female
mice. The result was negative when exposures were conducted at 5000
mg/kg body weight.

3\. Reproductive and Developmental Toxicity

### 

On long-term dietary administration, tribenuron methyl did not affect
the reproduction or lactation performance of rats. Developmental studies
in the rat and rabbit by gavage administration indicated that tribenuron
methyl did not present a unique toxic risk to the fetus.

There were no effects in reproduction or lactation in a one-generation
reproduction study with rats fed for 90 days with diets that contained
0, 100, 1750, or 5000 ppm active ingredient. The NOEL was 100 ppm (7
mg/kg/day for males and 8 mg/kg/day for females) based on lower mean dam
and pup body weights for the intermediate and high dose groups.

There were no effects on fertility observed in a 2-generation
reproduction study. In this study, rats were fed for at least 90 days
with diets that contained 0, 25, 250, or 1000 ppm active ingredient. The
NOEL was 25 ppm based on lower body weights for the dams and offspring
at 250 and 1000 ppm. There were no differences attributed to
administration of tribenuron methyl in the number of litters produced or
other indices of reproductive performance. No compound-related effects
on male fertility were noted. No effect on the number of pups born or
pup survival were observed in any tribenuron methyl treated group.

In a study to evaluate developmental toxicity potential in rats,
tribenuron methyl did not produce birth defects after administration via
oral intubation to pregnant rats at dose levels of 0, 20, 125, and 500
mg/kg/day. The NOEL for this study was 20 mg/kg/day for both maternal
and developmental toxicity. This was based on maternal effects at the
125 and 500 mg/kg/day. The effects included decreased body weight gain
and food consumption, and an increased incidence of excess salivation.
Fetal effects included decreased body weights (at 125 and 500 mg/kg/day)
and increased number of resorptions (only at 500 mg/kg/day). In the
rabbit developmental toxicity study, rabbits were fed dosage levels of
0, 5, 20, and 80 mg/kg/day. The NOEL for maternal and developmental
toxicity was 20 mg/kg/day. This was based on maternal effects, including
decreased feed consumption and an increased incidence of abortions at 80
mg/kg/day. Fetal effects included slightly reduced body weights at 80
mg/kg/day. No teratogenicity was observed.

4\. Subchronic Toxicity

The most sensitive species to subchronic exposure of tribenuron methyl
was the rat. In the rat study, rats were fed dosage levels of 0, 100,
1750 or 5000 ppm tribenuron methyl for 90 days. The findings show that
the NOEL for tribenuron methyl was 100 ppm for both male and female rats
(90-day dietary). This concentration is equivalent to 7 and 8 mg/kg/day
in male and female rats, respectively. The NOEL was based on the
decreased body weight and decreased feed consumption noted in the 1750
and 5000 ppm groups. The NOEL for the 90-day mouse feeding study was 500
ppm (70 mg/kg/day for males and 90 mg/kg/day for females) based on liver
and spleen effects at 1250, 2500, and 5000 ppm at 4 weeks. An increase
in liver weights at 2500 ppm was noted, with no histologic effects at
any level. The NOEL for subchronic (90-day dietary) exposure in dogs was
73 mg/kg/day for male and 78 mg/kg/day for female dogs. This was highest
dose tested, and no clear treatment related effects were observed. A
specific target organ was not identified in any of the species studied.

5\. Chronic Toxicity/Oncogenicity

The NOEL for chronic (18-month dietary) exposure in mice (males) was 20
ppm (equivalent to 3 mg/kg/day). This was based on an increased
incidence of bilateral seminiferous degeneration and oligospermia in the
mid- and high-dose groups. Within females, there was no LOAEL
established, but the minimal body weight reductions in the highest dosed
females suggested that the NOEL was 30 mg/kg/day. There were no
neoplastic or other histopathological effects associated with this
compound and no target organ was identified. Additionally, no evidence
of tribenuron methyl induced oncogenicity was observed in the mouse
study.

The NOEL for chronic (2-year dietary) exposure in rats was 25 ppm (0.95
and 1.2 mg/kg/day for male and female rats, respectively). Lower body
weight gains, which paralleled lower food consumption and organ weight
effects, were observed in the 250 and 1250 ppm groups. There were no
clinical or histopathological effects associated with these organ weight
effects. The incidence of mammary adenocarcinomas was greater than
controls for female rats in the 1250 ppm group. This effect was only
observed in this high-dose group and under conditions of significant
physiological stress (mean body weights for female rats were 43% lower
than the controls), which was determined to be above the maximum
tolerated dose (MTD).

In a 1-year feeding study in dogs, the NOEL was determined by DuPont to
be 250 ppm (8.16 and 8.18 mg/kg/day for male and female dogs,
respectively). This was based on slightly lower body weights and
increased serum creatinine concentrations for dogs in the high-dose
group (1500 ppm). Upon review by the EPA, the NOEL was set at 25 ppm
(0.8 mg/kg/day) based on observations such as elevated bilirubin blood
levels and reduction in body weight gain in male dogs. There were no
neoplastic or other histopathological effects associated with compound
administration.

6\. Animal Metabolism

The metabolism of tribenuron methyl was evaluated in rats using both
phenyl and triazine labeling. Tribenuron methyl was extensively and
rapidly converted to polar metabolites, and primarily excreted in the
urine and feces. Urinary excretion accounted for two to four times the
amount of radiolabel excreted via feces. Essentially all of the
tribenuron methyl and its metabolites were excreted in the urine and
feces of the rat within 96 hours after dosing. Levels of radiolabeled
residues in tissues were correspondingly higher in those groups with
slower elimination kinetics, but no evidence of bioconcentration was
seen. None of the dosed label was expired as carbon dioxide or volatile
metabolites.

The average excretion half-life values for male and female rats in the
low-dose group (20 mg/kg) were approximately the same (26-33 hours), and
independent of dietary preconditioning. The average excretion half-lives
for male and female rats in the high-dose groups (1700, 1800, and 2000
mg/kg) were approximately 51-54 hours (males) and 68-96 hours (females).
These results indicate that the metabolism of tribenuron methyl in male
and female rats is qualitatively similar, however, female rats
metabolize and excrete this product much slower than male rats at the
high doses. The low residual radioactivity in the rat indicated that
tribenuron methyl does not covalently bind to tissue macromolecules.
Based on these data, the body burden of this compound is not expected to
increase significantly upon repeated, long-term administration.

The major metabolites of tribenuron methyl are those expected from the
enzymatic hydroxylation and dealkylation activities of the hepatic
microsomal mixed function oxidase system. The major urinary metabolites
were identified as metsulfuron methyl and saccharin (phenyl labeled
groups) and metsulfuron methyl and O-demethyl triazine amine (triazine
labeled groups); no evidence of glucuronide or sulfate conjugation was
seen.

Results from a metabolism study with two radioactive forms of tribenuron
methyl (\[^14^C\]-triazine and \[^14^C\]-phenyl) in lactating goats show
that most of the dosed radioactivity was recovered in the urine (61-71%)
and feces (15-20%). In the urine, intact tribenuron methyl and
metsulfuron methyl accounted for 17-23% and 20-22% of the administered
dose, respectively. The third major component in phenyl-dosed goat urine
was saccharin (23.5% of the dose); the third major metabolite in the
triazine-dosed goat urine was O-demethyl N-demethyl triazine amine
(10.9%). The highest levels of residues observed in the milk were 0.09
ppm (tribenuron methyl equivalents) from the triazine-dosed goat, and
0.006 ppm from the phenyl-dosed goat. Recoveries of the administered
dose were 82.2% for the goat given the triazine label, and 86.8% for the
goat dosed with the phenyl label. Throughout the dosing phase, the goats
did not display any signs of toxicity, and there was no effect on milk
production.

There were no significant levels of unique plant metabolites of
tribenuron methyl found in food or feed products at crop maturity.
Hence, toxicity testing of other degradation products of tribenuron
methyl is not necessary.

7\. Metabolite Toxicology

There is no evidence that the metabolites of tribenuron methyl, as
identified in either the plant or animal metabolism studies, are of any
toxicological significance.

8\. Endocrine Effects

In the two-year study, female rats fed tribenuron methyl had a
significant increase in mammary adenocarcinoma incidence, but only at a
dose that greatly exceeded the maximum tolerated dose (43% decrease in
body weight). In contrast, an 18-month feeding study demonstrated that
tribenuron methyl was not oncogenic in mice, nor was there oncogenicity
in the rat study at doses which produced marked toxicity, but did not
exceed the maximum tolerated dose.

A subsequent mechanistic study was conducted at a dose level that
produced similar body weight gain decrements observed in the rat
oncogenicity study. This mechanistic study demonstrated an increased
incidence of rats with prolonged estrus and suggested that this may have
been associated with the high-dose mammary adenomas observed in the rat
oncogenicity study. However, the role of the body weight effect must be
considered in interpreting this data. Numerous studies have demonstrated
that nutritional deficits can also significantly impact the estrus
cycle. Such hormone-mediated effects are considered to have a threshold
below which growth of mammary tissue will not be affected. Thus
potential endocrine effects of tribenuron methyl are unlikely to be a
concern at biologically relevant doses. Adequate margins of safety
protect humans from these threshold effects.

C. Aggregate Exposure

Tribenuron methyl is the active ingredient in various DuPont herbicides,
with new proposed uses on the following commercial crops: sunflowers,
rice, field corn, soybeans, and grain sorghum. There are no residential
uses for any tribenuron methyl containing herbicides.

1\. Dietary Exposure

The chronic reference dose (cRfD) of 0.008 mg/kg/day is based on the
NOEL determined by EPA of 0.8 mg/kg/day from the one-year dog feeding
study and a 100X safety factor. Based on the acute toxicity profile of
tribenuron methyl, there are no acute effects. Non-specific clinical
signs and weight effects have been observed in developmental studies
after high, multiple doses. However, in the acute LD~50~ study conducted
at the limit dose of 5000 mg/kg, the only clinical sign observed was
stained perineum in some animals. Therefore no relevant acute dietary
endpoint attributable to a single dose was identified.

2\. Food

a\. Chronic Dietary Exposure Assessment

Chronic dietary exposure, resulting from the registered and proposed
uses of tribenuron methyl on barley, canola, cotton, flax, grass, oats,
wheat, rice, soybeans, grain sorghum, field corn, and sunflowers is well
within the acceptable limits for all sectors of the population, as
predicted by the Chronic Module of the Dietary Exposure Evaluation Model
(DEEM, Exponent, Inc., 2003 Version 7.87). 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 tribenuron 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
0.00021 mg/kg bw/d. The population subgroup with the highest predicted
level of chronic exposure was children 1- 6 years, with an exposure of
0.000477 mg/kg bw/day. Based on a chronic NOEL of 0.8 mg/kg bw/d and a
100-fold safety factor, the cRfD would be 0.008 mg/kg bw/d. For the U.S.
population, the predicted exposure is equivalent to 2.7% of the cRfD.
For the population subgroup with the highest level of exposure (children
1-6 years), the exposure would be equivalent to 6.0% 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 tribenuron methyl.

b\. Acute Dietary Exposure

Acute dietary risk assessments are performed for a food-use pesticide if
a toxicological study indicates the possibility of an effect of concern
as a result of a one day or a single exposure. No acute dietary endpoint
attributable to a single dose was identified for tribenuron methyl.
Therefore the quantification of acute dietary risk is not considered
necessary. There is reasonable certainty that no acute effects would
result from dietary exposure to tribenuron methyl.

3\. Drinking Water

Surface water exposure was estimated using the Generic Expected
Environmental Concentration (GENEEC) model. Groundwater exposures were
estimated using SCI-GROW.

The 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. Since there are no residential uses for tribenuron methyl, the
aggregate exposure is due to food and water only. 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. Default body weights and consumption values, as used by
the USEPA Office of Water, used to calculate the DWLOC values for
tribenuron methyl are: 70kg and 2L (adult male), 60 kg and 2L (adult
female), and 10 kg and 1L (child).

No acute dietary endpoint was identified. Therefore, an acute drinking
water risk assessment is not considered necessary. One can conclude with
reasonable certainty that residues of tribenuron methyl in drinking
water do not contribute significantly to the aggregate acute human
health risk.

The chronic DWLOCs are 0.28 ppm for adult men, 0.24 ppm for adult women,
and 0.08 ppm for children 1-2 years old. These DWLOC values are
substantially higher than the GENEEC 56-day estimated environmental
concentration of 0.3 ppb for tribenuron methyl in surface water,
estimated concentrations in ground water are even lower. Therefore, one
can conclude with reasonable certainty that residues of tribenuron
methyl in drinking water do not contribute significantly to the
aggregate chronic human health risk.

4\. Non-Dietary Exposure

Tribenuron methyl is not registered for any use which could result in
non-occupational or non-dietary exposure to the general population.

D. Cumulative Effects

Tribenuron methyl belongs to the sulfonylurea class of crop protection
chemicals. Other structurally similar compounds in this class are
registered as 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
tribenuron methyl has any toxic effects on mammals that would be
cumulative with those of any other chemical.

E. Safety Determination

Based on data and information submitted by DuPont, EPA previously
determined that the establishment of tolerances of tribenuron methyl on
wheat, barley, oats, cotton, canola, flax, and grass raw agricultural
commodities would protect the public health, including the health of
infants and children. Establishment of new tolerances for tribenuron
methyl on sunflowers at 0.05 ppm, field corn commodities at 0.05 ppm,
grain sorghum commodities at 0.05 ppm, rice commodities at 0.05 ppm, and
soybean seed at 0.05 ppm will not adversely impact public health.

1\. U.S. Population

Using the conservative exposure assumptions described above, and based
on the most sensitive chronic NOEL of 0.79 mg/kg/day and a cRfD of 0.008
mg/kg/day, the chronic dietary exposure will utilize 2.7 % of the cRfD
for the U.S. population. Generally, exposures below 100 % of the RfD are
of no concern because the RfD represents the level at or below which
daily dietary exposure over a lifetime will not pose risk to human
health. Therefore, it is concluded that there is reasonable certainty
that no harm will result from exposure to tribenuron methyl residues.

2\. Infants and Children

Chronic dietary exposure of the most highly exposed subgroup in the
population, children 1-6 years old, is 0.000477 mg/kg/day, or 6.0 % of
the cRfD. There are no residential uses of tribenuron methyl and
contamination of drinking water is extremely unlikely. Based on the
completeness and reliability of the toxicity data, the lack of
toxicological endpoints of special concern, the lack of any indication
of greater sensitivity of children, and the conservative exposure
assessment, there is a reasonable certainty that no harm will result to
infants and children from the aggregate exposure to residues of
tribenuron methyl from all anticipated sources of dietary and
non-occupational exposure. Accordingly, there is no need to apply an
additional safety factor for infants and children.

F. International Tolerances

The MRL in Canada for tribenuron methyl on canola is 0.1 ppm. Tolerances
for tribenuron methyl on cereals, barley, and/or wheat commodities have
been established or proposed in other countries -- for example in
Greece, France, Italy, Portugal, Spain and the United Kingdom at levels
ranging from 0.01 to 0.2 ppm. No Codex maximum residue limits (MRLs)
have been established or proposed.