Document ID: EPA-HQ-OPP-2009-0134-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-20T04:00Z

EPA Registration Division Contact: Susan Stanton, 703-305-5218

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

PP No. 9F7523

EPA has received a pesticide petition (PP No. 9F7523) from Interregional
Research Project Number 4 (IR-4), IR-4 Headquarters, Rutgers, The State
University of New Jersey

500 College Road East, Suite 201-W, Princeton, NJ 08540-6635, 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 180.439 by establishing a
tolerance for residues of the herbicide thifensulfuron methyl
{Methyl-3-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl) amino] carbonyl]
amino] sulfonyl] -2-thiophenecarboxylate} in or on the following raw
agricultural commodities: Safflower (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

1a. Plant Metabolism

The qualitative nature of the residues of thifensulfuron methyl in
plants is adequately understood, therefore no additional metabolism data
are required to support the proposed tolerance on safflower seed. Three
plant metabolism studies – in wheat, corn, and soybeans - were
conducted. Crops were treated with [thiophene-2-14C] and
[triazine-2-14C] thifensulfuron methyl via direct foliage application.
[14C] Thifensulfuron methyl was rapidly metabolized in all three crops,
and the nature of the metabolites was essentially the same regardless of
the crop. In all three crops, metabolism involved cleavage of the urea
bridge, metabolism (O-demethylation) of the methoxy group on the
triazine ring, and hydrolysis of the methyl ester group on the thiophene
ring. Minor differences in the formation and decline of short-lived
intermediates were observed, however these differences were not
environmentally significant because of the low levels of these
intermediate metabolites in the crops. 

Metabolism studies conducted with 14C-thifensulfuron methyl on wheat (at
a rate of approximately 28-30 g ai/acre) under field conditions showed
no significant residues of thifensulfuron methyl or its degradation
products (i.e., all less than 0.01 ppm) in wheat grain at maturity.
Mature straw total residues were 0.45 to 0.80 ppm for the triazine and
thiophene-labeled tests, respectively.  Metabolites in wheat straw
included thifensulfuron methyl, thifensulfuron acid, O-demethyl
thifensulfuron methyl, 2-ester-3-sulfonamide, 2-acid-3-sulfonamide,
triazine urea, triazine amine, and O-demethyl triazine amine. Complete
breakdown of [14C]thifensulfuron methyl and/or metabolites resulting in
re-incorporation of the radiolabel into natural plant constituents
(e.g., sugars) was also observed. No single metabolite was greater than
0.06 ppm in the mature wheat straw.

Metabolism studies with [14C]thifensulfuron methyl were conducted (at a
rate of approximately 14 g ai/acre) in field grown corn. There were no
detectable residues of thifensulfuron methyl or its transformation
products in corn grain (i.e., all less than 0.01 ppm) or foliage (i.e.,
all less than 0.02 ppm) at maturity.  Analysis of non-mature foliar
samples showed rapid and extensive metabolism of thifensulfuron methyl. 
Among the residues detected were thifensulfuron methyl,
2-acid-3-sulfonamide, triazine urea, triazine amine, O-demethyl triazine
urea, and O-demethyl triazine amine. Thifensulfuron acid and
2-ester-3-sulfonamide, which are metabolites seen in other plant
metabolism studies (wheat and soybean), were not detected, but were most
likely transient intermediates (both plausible precursors to
2-acid-3-sulfonamide) in the corn plants.

Metabolism studies were conducted with soybeans under greenhouse
conditions (at rates of 3 and 6 g ai per acre). There were no detectable
residues (i.e., all less than 0.01 ppm) in the beans or pods at either
rate at final harvest.  Analysis of non-mature foliar samples showed
extensive metabolism of thifensulfuron methyl.  Residues detected
included thifensulfuron methyl, thifensulfuron acid,
2-ester-3-sulfonamide, 2-acid-3-sulfonamide, triazine amine, and
O-demethyl triazine amine. 

1b. Confined Rotational Crop Studies

Two different crop rotation scenarios were investigated, one involving a
bare ground application, the other with a cover crop (wheat). No
significant difference in metabolic profile was observed in the rotated
crops (beets, peas, and sunflowers) under either scenario. No
thifensulfuron methyl (i.e., <0.01 mg/kg) was detected in any food or
feed item from any of the rotated crops.

A confined greenhouse crop rotation study (following application to bare
soil) was conducted with thiophene-14C thifensulfuron methyl by planting
beets, peas, and sunflowers at either a 30 or 120 day
treatment-to-planting interval. The application rate used was 35 - 38 g
ai/acre. Total soil residue levels at planting were low, 0.01 – 0.02
mg/kg for both the 30- and 120-day aging periods. Levels of
thifensulfuron methyl at planting accounted for <0.01 mg/kg at the end
of each aging period. There were no significant residues (i.e., all less
than 0.005 ppm) in food items (beet root, peas, sunflower seeds) in
crops planted 30 or 120 days following soil treatment. There were minor
detectable residues (0.02 to 0.05ppm) in animal feed items (beet foliage
and sunflower foliage). Thifensulfuron methyl was only identified (<0.01
ppm) in sunflower foliage 73 days after treating the soil; other minor
components observed were polar.

A confined greenhouse crop rotation study (following triazine-14C
thifensulfuron methyl treated wheat) was conducted using beet root,
peas, pea pods, and sunflower as following crops. The study used an
application rate of 15 g ai/acre, and a 45 or 75 day
treatment-to-planting interval. At the end of the 45- and 75-day aging
periods (after incorporation of the cover crop), soil residue levels
were 0.01 – 0.02 mg thifensulfuron methyl equivalents per kg of soil.
Thifensulfuron methyl was not detected in the soil after 45 days;
triazine urea was the principal soil component at the 45- and 75-day
planting interval. There were no substantial residues (i.e., all less
than 0.01 ppm) in food items (beet root, peas, pea pods, sunflower
(seeds and heads) in crops planted 45 or 75 days following treated wheat
incorporation into the soil.  There were minor detectable residues in
animal feed items.  Sunflower and pea foliage contained 0.04 – 0.05
ppm and 0.01 - 0.02 ppm for the 45 and 75 day planting, respectively. 
Small amounts of triazine amine (< 0.03 ppm), triazine urea, and
O-demethyl triazine amine were identified in these fractions.  

2. Analytical Methods

Samples were analyzed for residues of thifensulfuron-methyl using Liquid
Chromatography.

 

Summarizing briefly for the safflower seed and meal analyses,
thifensulfuron-methyl residues were extracted from the samples by
soaking ground tissue in sodium bicarbonate for a minimum of 2 hr, then
adjusting the pH to 3.5. The mixture was homogenized in dichloromethane.
The organic solvent was isolated and extracted three times with sodium
bicarbonate. The resulting aqueous extracts were combined, rinsed with
hexane and adjusted to pH 3.0 – 3.5 with HCl. This acidic solution was
further cleaned by retention on a C18 solid phase extraction cartridge
with a rinse of water followed by a rinse with methanolic acetic acid in
water, and finally, eluted with methanolic acetic acid in water. The
analyte was then partitioned in dichloromethane, and the organic layer
was dried and reconstituted with a portion of dichloromethane prior to
loading onto a CN solid phase extraction cartridge. The analyte was
eluted with ethyl acetate in dichloromethane. The eluate was dried and
reconstituted in n-hexane-isopropyl alcohol prior to analysis by
high-performance liquid chromatography with photo-conductivity
detection. The method described above was used for the safflower oil
with modifications. Most notably, both the oil and the analyte are very
soluble in dichloromethane, so soaking with sodium bicarbonate was not
required. As a result, the extraction and isolation procedure for oil
was simplified by initiating the isolation with the back-extraction from
dichloromethane into sodium bicarbonate and following the procedure from
that point. 

The lowest level of method validation (LLMV) for each matrix in this
study, i.e., safflower seed, meal and oil, was 0.05 ppm of
thifensulfuron-methyl. The limits of quantitation (LOQ) for the method
for safflower seed was 0.027 ppm of thifensulfuron-methyl. The estimated
LOQ for meal and oil were calculated at 0.039 ppm, and 0.0068 ppm of
thifensulfuron-methyl, respectively. The limits of detection (LOD) for
the method for safflower seed was 0.0090 ppm of thifensulfuron-methyl.
The estimated LOD for meal and oil were 0.013 ppm, and 0.0023 ppm of
thifensulfuron-methyl, respectively.

All samples were analyzed between 1 and 6 days from extraction with the
exception of the freezer storage set for safflower meal which was
analyzed 23 days after extraction. 

3. Magnitude of Residue

	

Safflower

Field tests were conducted on safflower (seed, meal, and oil). The
maximum residue in seed following an application of 0.0176-0.0187 lb
ai/A and a pre-harvest interval (PHI) of 36-81 days was <0.05 ppm. The
maximum residue in meal and oil following an application of 0.0186 lb
ai/A and a pre-harvest interval (PHI) of 81 days was <0.05 ppm.

B. Toxicological Profile

1. Acute Toxicity

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

	Acute oral toxicity in rats			LD50 > 5000 mg/kg

	Acute dermal toxicity in rabbits		LD50 > 2000 mg/kg

	Acute inhalation toxicity in rats		LC50 > 7.9 mg/L

	Primary eye irritation in rabbits		Moderate irritation

	Primary dermal irritation in rabbits		Slight irritation

	Dermal sensitization in guinea pigs		Non-sensitizer

2. Genotoxicity

Technical thifensulfuron methyl has shown no genotoxic or mutagenic
activity in the following  in vitro and in vivo tests :

	In vitro Mutagenicity Ames Assay		Negative

	In vitro Mutagenicity CHO/HPRT Assay	Negative

In vitro Unscheduled DNA Synthesis		Negative

	In vivo Micronuclei Induction (Mouse) 	Negative

	In vivo Bone Marrow Chromosome

	  Aberrations (Rat)				Negative

	

Thifensulfuron methyl was not mutagenic, with or without metabolic
activation, in an in vitro bacterial gene mutation assay using
Salmonella typhimurium. Thifensulfuron methyl also was not mutagenic in
the in vitro CHO/HPRT assay at concentrations up to 2712 mg/L (in
Chinese hamster ovary cells).  In cultured primary rat hepatocytes,
thifensulfuron methyl was negative for the induction of unscheduled DNA
synthesis up to 2712 mg/L.

An in vivo bone marrow micronucleus test was conducted in mice. There
was no increase in micronucleated polychromatic erythrocytes (MNPCE)
frequency at a dose of 5000 mg/kg. An in vivo chromosome aberration
study was conducted on rats.  This included the assessment of chromosome
aberrations by metaphase analysis in bone marrow of male and female
rats. 

Thifensulfuron methyl did not induce cytogenic damage in bone marrow
cells at a dose of 5000 mg/kg.

3. Reproductive and Developmental Toxicity

The results of a series of studies indicated that there were no
reproductive, developmental or teratogenic hazards associated with the
use of thifensulfuron methyl. In a 1-generation reproduction study in
rats, the suggested NOEL was 7500 ppm (559 mg/kg/day males, 697
mg/kg/day females). In a rat multigeneration reproduction study, the
NOEL for reproductive effects of thifensulfuron methyl in adult rats and
their offspring was 2500 ppm, the highest dietary level tested.  This
level was based on the absence of significant compound related effects
observed in this study, and is equivalent to 175-180 mg/kg/day in adult
male rats and 212-244 mg/kg/day in adult female rats.  There were no
effects on fertility, lactation, litter size, or pup survival.
Thifensulfuron methyl is not considered a reproductive toxin.

In studies conducted to evaluate developmental toxicity potential,
thifensulfuron methyl was neither teratogenic nor uniquely toxic to the
conceptus (i.e., not considered a developmental toxin). In the rat
study, there was no evidence of maternal toxicity at the highest dose
tested (800 mg/kg/day). Therefore, the maternal NOAEL is 725 mg/kg/day
(analytically determined dose). The developmental NOAEL for rats was
considered to be the 200 mg/kg/day dose level (analytically determined
and set by EPA as 159 mg/kg/day) based on the decrease in mean fetal
body weight and an increase in the incidence of small renal papillae. In
the rabbit developmental toxicity study, there was slight maternal
toxicity (decreased body weight gain) at a dose of 650 mg/kg/day.  No
significant indications of maternal toxicity were evident at the
mid-dose level (200 mg/kg/day).  No compound-related effects on fetal
weights or the incidences of malformations or variations were seen at
any dose. The maternal NOEL was the 200 mg/kg/day dose (analytically
determined and set by EPA at 158 mg/kg/day) and the developmental NOEL
was the 650 mg/kg/day dose level (analytically determined and set by EPA
at 511 mg/kg/day) for rabbits dosed with thifensulfuron methyl by gavage
on gestation days 7-19. 

4. Subchronic Toxicity

The most sensitive species to subchronic exposure of thifensulfuron
methyl was the rat. The NOEL for thifensulfuron methyl was 100 ppm (7
and 9 mg/kg/day) for male and female rats, respectively, in the 90-day
dietary study. This was based on the decreased body weight, food
efficiency, and changes in clinical chemistry in the 2500 and 7500 ppm
groups. For mice in both the 4-week range-finding and the 90-day
studies, the NOEL for male and female mice under the conditions of this
study was 7500 ppm. This was based on the lack of compound-related
effects at the highest concentration, equivalent to 1427 mg/kg/day in
male mice and 2287 mg/kg/day in female mice. EPA concluded the NOEL for
subchronic (90-day dietary) exposure in dogs was 1500 and 7500 ppm in
males and females (equivalent to 37.5 mg/kg/day and 159.7 mg/kg/day)
respectively. These levels were based on lower body weight and adrenal
weight in males, and a lack of adverse effects in females at 7500 ppm,
the highest concentration tested. No compound-related pathologic lesions
were observed and no target organ was identified in all of the above
tests.

	

5. Chronic Toxicity/Oncogenicity  

		

The NOEL for chronic (2-year dietary) exposure in rats was 500 ppm (20
mg/kg/day for males and 26 mg/kg/day for females), based on body weight
effects at 2500 ppm. Thifensulfuron methyl was not an oncogen in rats.

In an 18-month study in mice, conducted at dietary levels of 0, 25, 750,
and 7500 ppm, EPA concluded the NOEL was 25 ppm (4.3 mg/kg/day) based on
decreased body weight gains in female mice at 750 ppm and above, and in
male mice at 7500 ppm. No other effects were observed in the study.
Thifensulfuron methyl was not an oncogen in mice. 

	

In a 1- year feeding study in dogs, the NOEL of thifensulfuron methyl
was 750 ppm in male and female beagle dogs (equivalent to approximately
18.75 mg/kg/day), based on decreased body weights, body weight gains,
and food efficiency in females and increased liver weights in males, all
at 7500 ppm.  The liver weight effects in males in the absence of other
effects including histopathology may be adaptive rather than adverse. 

6. Animal Metabolism

The metabolic pathway for thifensulfuron methyl in animals is
understood. This metabolic pathway involves hydrolysis of the urea
bridge, deesterification, and O-demethylation reactions. There was
minimal potential for retention or accumulation of thifensulfuron methyl
or its metabolites in animal tissues. Low levels of thifensulfuron
methyl residues were found in goat tissues and insignificant tissue
levels (i.e., less than 0.1% of the dose) were observed in the rat. 

Rats were dosed with two radioactive forms of thifensulfuron methyl
(14C-thiophene and 14C-triazine).  In the thiophene study, the
thifensulfuron methyl was primarily excreted unchanged by rats following
low dose (20 mg/kg), low dose following 21 days dietary preconditioning 
(100 ppm), and high dose (2,000 mg/kg) routines. Approximately 70% to
85% of the excreted radioactivity was thifensulfuron methyl. The urine
was the primary excretion route and contained 71% to 92% of the original
dose from the low and low-dose preconditioned groups. Combined urinary
and fecal elimination was rapid, with over 90% of excretion completed by
48 hours after dosing for both low-dose groups. The high-dose group peak
elimination was delayed by approximately 24 hours compared to the other
dose levels. Tissue radioactivity levels were low at sacrifice (96 hours
after dosing) for all dosing groups, with no enhanced retention of
radioactivity by any organ or tissue. Thifensulfuron methyl was the
primary radiolabeled excretion product with thifensulfuron acid,
2-acid-3-sulfonamide, 2-ester-3-sulfonamide, and thiophene sulfonamide
identified as minor metabolites. 

In the triazine study, thifensulfuron methyl was excreted primarily
unchanged in urine and feces by male and female rats after
administration of approximately 2000 mg/kg by oral gavage. Urine was the
primary route of excretion, averaging 58.7% of the dose in males and
75.5% in females. Fecal excretion of the dose averaged 21.2% for the
male rats and 15.8% for the females. Greater than 50% of the dose was
excreted by 48 hours post-dosing. Essentially no elimination of the dose
as radiolabeled CO2 or volatile compounds occurred. These results are
similar to those reported on the thiophene-labeled thifensulfuron
methyl. Intact thifensulfuron methyl was identified by mass spectrometry
as the principal radioactive compound in urine (> 94%) and feces (>
77%). Three minor metabolites, each less than 3% of the dose, were
identified in urine and feces by chromatographic retention comparison;
they were thifensulfuron acid, O-demethyl thifensulfuron methyl, and
triazine amine.

Results from a metabolism study with two radioactive forms of
thifensulfuron methyl (14C-triazine and 14C-thiophene) in lactating
goats show that most of the dosed radioactivity was rapidly excreted
(primarily in the urine) and recovered as intact thifensulfuron methyl.
Radioactivity in the milk (0.1 - 0.2 ppm) was comprised of mostly intact
thifensulfuron methyl and a small amount of triazine amine and several
very minor metabolites. Radioactivity did not accumulate in the tissues.
After absorption, the major metabolic pathway involved cleavage of the
carboxyl ester linkage, resulting in the formation of thifensulfuron
acid.  Oxidative O-demethylation occurred to a limited extent.  

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

7. Metabolite Toxicology

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

8. Endocrine Effects

No special studies investigating potential estrogenic or other endocrine
effects of thifensulfuron methyl have been conducted. However, the
standard battery of required toxicology studies has been completed.
These include an evaluation of the potential effects on reproduction and
development, and an evaluation of the pathology of the endocrine organs
following repeated or long-term exposure to doses that far exceed likely
human exposures. Based on these studies, there is no evidence to suggest
that thifensulfuron methyl has an adverse effect on the endocrine
system.

C. Aggregate Exposure

Thifensulfuron methyl is the active ingredient in a number of DuPont
herbicides, with new tolerances being proposed in/on barley hay, wheat
forage and hay, and oat forage and hay, to support the currently
registered use of this active ingredient on these crops. There are no
residential uses for any thifensulfuron methyl containing herbicides.

1. Dietary Exposure

The chronic reference dose (cRfD) of 0.2 mg/kg/day is based on the NOEL
of 20 mg/kg/day from a two-year rat feeding study and a 100X safety
factor.  The acute reference dose (aRfD) of 1.59 mg/kg/day is based the
NOEL of 159 mg/kg/day from a rat developmental study and a 100X safety
factor.

The residue of concern, as listed at 40 CFR 180.439, is parent
thifensulfuron methyl only.

2. Food

a. Chronic Dietary Exposure Assessment

Dietary exposure, resulting from the current and proposed uses of
thifensulfuron methyl on barley, canola, cotton, flax, field corn, oats,
soybeans, sorghum, rice, wheat, and safflower is well within the
acceptable limits for all sectors of the population, as predicted by
both the Chronic and Acute Modules of the Dietary Exposure Evaluation
Model with Food Commodity Intake Database (DEEM-FCIDTM, Exponent, Inc.,
2003 Version 2.14).  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 all crops that 100% was treated with
thifensulfuron methyl.  Based on a comparison with the actual use
profiles for herbicides containing thifensulfuron methyl, this is an
extremely conservative estimate.

The predicted chronic exposure for the U.S. population was 0.000226
mg/kg bw/day.  The population subgroup with the highest predicted level
of chronic exposure was the children 3-5 years subgroup with an exposure
of 0.000517 mg/kg bw/day.  Based on a chronic NOEL of 20 mg/kg bw/day
and a 100-fold safety factor, the cRfD would be 0.2 mg/kg bw/day.  For
both the U.S. population and the children 3-5 years subgroup, the
predicted exposure is equivalent to less than 1% of the cRfD.  Since the
predicted exposures, expressed as percentages of the cRfD, are well
below 100%, there is reasonable certainty that no chronic effects would
result from dietary exposure to thifensulfuron methyl.

b. Acute Dietary Exposure

The predicted acute exposure for the U.S. population subgroup was
0.000574 mg/kg bw/day (95th percentile).  The population subgroup with
the highest predicted level of acute exposure was the infants subgroup
with an exposure of 0.001062 mg/kg bw/day (95th percentile).  Based on
an acute NOEL of 159 mg/kg bw/day and a 100-fold safety factor, the aRfD
would be 1.59 mg/kg bw/day.  For both the U.S. population and the
infants subgroup the predicted exposure (at the 95th percentile) is
equivalent to less than 1% of the aRfD.  Since the predicted exposures,
expressed as percentages of the aRfD, are well below 100%, there is
reasonable certainty that no acute effects would result from dietary
exposure to thifensulfuron methyl.

3. Drinking Water

Surface water exposure was estimated using the Generic Expected
Environmental Concentration (GENEEC) model, and groundwater exposures
were estimated using SCI-GROW.  There was little change from the
food-only dietary risk assessments when the higher surface water
concentrations were included in the acute and chronic dietary risk
assessments.  When the estimated maximum concentration of thifensulfuron
methyl in surface water, 1.2 parts per billion (ppb), was included in
the acute dietary assessment as a point estimate the predicted exposure
at the 95th percentile for the general U.S. population was 0.000608
mg/kg/day which corresponds to less than 1% of the aRfD; the most
sensitive subpopulation, infants, had an estimated exposure at the 95th
percentile of 0.001187 mg/kg/day, less than 1% of the aRfD.   
Therefore, one can conclude with reasonable certainty that residues of
thifensulfuron methyl in drinking water do not contribute significantly
to the aggregate acute human health risk.

When the GENEEC 56-day estimated environmental concentration of 0.65 ppb
thifensulfuron methyl in surface water was included in the chronic
dietary assessment, the predicted exposure for the general population
was 0.000239 mg/kg/day, less than 1% of the cRfD; the most sensitive
subpopulation, children 3-5 years, had an estimated exposure of 0.000536
mg/kg/day, less than 1% of the cRfD.  Thus, it can be concluded that the
chronic dietary exposure of thifensulfuron methyl, including the
contribution of drinking water, clearly meets the standard of reasonable
certainty of no harm.  

4. Non-Dietary Exposure

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

D. Cumulative Effects

Thifensulfuron methyl belongs to the sulfonylurea class of crop
protection chemicals. Other structurally similar compounds in this class
are registered 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
thifensulfuron 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 thifensulfuron methyl
on the barley, oats, wheat, field corn, cotton, canola, flax, soybean,
rice, and sorghum raw agricultural commodities would protect the public
health, including the health of infants and children.

Establishment of a new tolerance for thifensulfuron methyl on Safflower
at 0.05 ppm will also not adversely impact public health.

 

1. U.S. Population

	

Based on the completeness and reliability of the toxicology database,
and using the conservative assumptions presented earlier, EPA has
established a cRfD of 0.2 mg/kg/day. This was based on the NOEL for the
chronic rat study, 20 mg/kg/day, and a 100-fold safety factor. It has
been concluded that the chronic dietary exposure was less than 1% of the
cRfD.  Generally, exposures below 100% of the cRfD are of no concern
because it represents the level at or below which daily dietary exposure
over a lifetime will not pose appreciable risk to human health. Thus,
there is reasonable certainty that no harm will result from chronic
exposures to thifensulfuron methyl residues.

2. Infants and Children

In assessing the potential for additional sensitivity of infants and
children to residues of thifensulfuron methyl, data from the previously
discussed developmental and multigeneration reproductive toxicity
studies were considered. 

Developmental studies are designed to evaluate adverse effects on the
developing organism resulting from pesticide exposure during pre-natal
development. Reproduction studies provide information relating to
reproductive and other effects on adults and offspring from pre-natal
and post-natal exposures to the pesticide. The studies with
thifensulfuron methyl demonstrated no evidence of developmental toxicity
at exposures below those causing maternal toxicity.  This indicates that
developing animals are not more sensitive to the effects of
thifensulfuron methyl administration than adults.  

FFDCA section 408 provides that EPA may apply an additional uncertainty
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
database.  Based on current toxicological data requirements, the
database for thifensulfuron methyl relative to pre- and post-natal
effects for children is complete.  In addition, the NOEL of 20 mg/kg/day
in the chronic rat study (and upon which the RfD is based) is much lower
than the NOELs defined in the reproduction and developmental toxicology
studies.  The sub-population with the highest level of chronic exposure
was Children 3-5 years, for whom exposure was less than 1% of the cRfD.
Based on these conservative analyses, there is reasonable certainty that
no harm will result to infants and children from aggregate exposures to
thifensulfuron methyl. 

F. International Tolerances

The maximum residue limit (MRL) in Canada for thifensulfuron methyl on
canola is 0.1 ppm. The MRLs in the EU (European Union) are 0.05 ppm for
barley, field corn (maize), oats, soybeans (soya bean), wheat, canola
(rapeseed), cotton seed, flax (other oilseeds), rice, sunflowers, and
sorghum.

Pesticide Petition for Tolerances for		AGRICULTURAL COMMODITIES

Thifensulfuron Methyl		Safflower

		

E.I. du Pont de Nemours and Company

Wilmington, DE 19880-0038 

December 2008