UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF 

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: September 24, 2003

MEMORANDUM

Subject: Human Health Risk Assessment for the Section 3 Registration of Trifloxysulfuronsodium on Almond, Citrus, Cotton, Sugarcane, Tomato, and Turf. PP# 1F06280. 

DP Barcode: D284104 Submission: S618179

PC Code: 119009 Case: 294017

40 CFR 180: None (new a.i.) Class: Sulfonylurea Herbicide

From: Michael Doherty, Chemist

Edwin Budd, Toxicologist

Alan Levy, Toxicologist

Shih-Chi Wang, Biologist

Registration Action Branch 2

Health Effects Division (7509C)

Through: Gary Bangs, Industrial Hygenist

Yan Donovan, Chemist

Registration Action Branch 2

Health Effects Division (7509C)

Through: Richard Loranger, Branch Senior Scientist

Registration Action Branch 2

Health Effects Division (7509C)

To: Jim Tompkins/Vickie Walters (25)

Herbicide Branch

Registration Division (7505C)
i

1.0 EXECUTIVE SUMMARY ................................................... 1

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION ................... 4

3.0 HAZARD CHARACTERIZATION ............................................ 5

3.1 Hazard Profile ....................................................... 5

3.2 FQPA Considerations ................................................ 10

3.3 Dose-Response Assessment ............................................ 11

3.4 Endocrine Disruption ................................................. 15

4.0 EXPOSURE ASSESSMENT ................................................ 15

4.1 Summary of Proposed Uses ............................................ 15

4.2 Dietary Exposure/Risk Pathway ........................................ 18

4.2.1 Residue Profile .............................................. 18

4.2.2 Acute and Chronic Dietary Exposure and Risk ..................... 19

4.3 Water Exposure/Risk Pathway ......................................... 20

4.4 Residential Exposure/Risk Pathway ..................................... 21

4.4.1 Home Uses ................................................. 21

4.4.2 Recreational ................................................ 22

4.4.3 Other (Spray Drift, etc.) ....................................... 22

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION .......... 22

5.1 Acute Risk ......................................................... 23

5.2 Short-Term Risk..................................................... 24

5.3 Intermediate-Term Risk ............................................... 25

5.4 Chronic Risk ....................................................... 25

5.5 Cancer Risk ........................................................ 26

6.0 CUMULATIVE RISK ...................................................... 26

7.0 OCCUPATIONAL EXPOSURE .............................................. 27

8.0 DATA NEEDS AND LABEL REQUIREMENTS ................................ 30

8.1 Toxicology ........................................................ 30

8.2 Residue Chemistry ................................................... 30

8.3 Occupational and Residential Exposure .................................. 31
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1.0 EXECUTIVE SUMMARY

Note: Throughout this document, “trifloxysulfuron-sodium” refers, specifically, to the

sodium salt and “trifloxysulfuron” refers to the free acid form of the molecule.

Syngenta Crop Protection, Inc. has requested that the Agency grant a national registration

for the use of the herbicide trifloxysulfuron-sodium on almonds, citrus, cotton, sugarcane,

tomatoes, and turf, and establish tolerances for residues for trifloxysulfuron on almond, citrus,

cotton, sugarcane, and tomato commodities. For cotton and sugarcane, trifloxysulfuron-sodium

may be applied as a post-emergent over-the-top spray or as a directed spray at a total rate not to

exceed 0.019 (cotton) or 0.07 (sugarcane) lb active ingredient (ai)/A per season. For established

almond and citrus orchards, applications to the orchard floor may be made pre-emergent and/or

post-emergent and may not exceed 0.056 lb ai/A/season. For tomatoes, post-emergent broadcast

spray may be used prior to transplant and/or post-emergent directed spray following transplant. 

The total seasonal rate for tomatoes is not to exceed 0.014 lb ai/A. For turf, use is restricted to

golf courses only and will not exceed 0.026 lb ai/A per season. Trifloxysulfuron-sodium is not

to be applied aerially or via any type of irrigation system (chemigation).

Trifloxysulfuron-sodium is a sulfonylurea herbicide that is intended to control or

suppress a number of weeds including sedges, pigweeds, morning glory, and a variety of grasses. 

Like other sulfonylurea herbicides, trifloxysulfuron-sodium is highly toxic to susceptible plants

and acts by inhibiting acetolactate synthase. This enzyme occurs only in plants. The leaves of

susceptible plants typically turn yellow, red, or purple several days after application. Complete

plant death occurs 1-3 weeks after application, depending on the species and environmental

conditions.

Estimating risks from chemicals involves assessing both the hazard of the chemical by

examining its toxicity, and exposure to the chemical by examining residues and various activities

(eating, working, playing, etc.). The Health Effects Division (HED) has examined adequate

toxicological and residue chemistry data submitted to support the registration of trifloxysulfuronsodium. In mammals, trifloxysulfuron-sodium was shown to adversely affect the kidneys, the

urinary bladder, the liver, heart development, body weight gain, motor activity, and lung tissue at

relatively high dose levels. HED has used No Observed Adverse Effect Levels as the basis for

the hazard component of this risk assessment. No Observed Adverse Effect Levels (NOAELs)

are the highest dose levels in toxicological studies that did not cause adverse effects to the test

animals. To ensure that risk estimates are protective of human health, HED has applied

uncertainty factors to account for variability of toxicity within species and between species to the

NOAELs. HED has considered the potential for enhanced sensitivity of infants and children to

chemical effects. Developmental studies with rabbits show that infants and children may be

more sensitive than adults to the effects of trifloxysulfuron-sodium, and this information has

been incorporated into the risk assessment. Despite the noted effects and the potential sensitivity

to infants and children, trifloxysulfuron-sodium exhibits relatively low toxicity in mammals. 

Trifloxysulfuron-sodium is classified as not likely to be carcinogenic to humans.
2 of 32

Residue chemistry data are sufficient to assess the potential exposure to trifloxysulfuron

from food and drinking water. Because trifloxysulfuron-sodium is highly toxic to plants, it is

applied at very low rates, and high concentrations of this chemical are not expected in foods. 

The residue chemistry data show that trifloxysulfuron was typically not detectable in studies

designed to maximize the potential for residues of this compound in human foods and livestock

feedstuffs. Because appropriate studies with clear NOAELs are used directly in this risk

assessment to address the sensitivity of infants and children and the exposure data used in the

assessment will not underestimate exposure, the special safety factor mandated by the Food

Quality Protection Act of 1996 has been reduced from 10 to 1.

Trifloxysulfuron-sodium may be applied to golf-course turf as well as to agricultural

crops; therefore, there is the potential for people to be exposed to this herbicide during golfing as

well as through their diet. HED has performed an aggregate assessment that includes exposure

from these two pathways. For the dietary exposure, the recreational exposure, and the aggregate

exposure, HED is reasonably certain that no adverse human health effects will occur in the U.S.

population or in any population subgroup, including those of infants and children, from the

requested uses of trifloxysulfuron-sodium.

HED has also assessed the potential risks to workers involved in applying

trifloxysulfuron-sodium or working in fields treated with the herbicide. Assuming that these

workers are wearing minimal protection (e.g., shirt, pants, socks, shoes), the risks associated

with exposure to trifloxysulfuron from these activities are minimal and are not cause for concern.

HED has a high degree of confidence in the data submitted to support the registration of

trifloxysulfuron-sodium on the commodities addressed by Petition 1F06280. The risk estimates

resulting from those data and presented in this assessment are, overall, highly conservative and

likely overestimate the actual risks to the U.S. population, its various subgroups, and agricultural

workers from the requested uses of this herbicide. Even with this overestimation, these risk

estimates are all well below HED’s level of concern. HED recommends that the 75% ai WG

formulation of trifloxysulfuron-sodium be granted a conditional registration for use on almond,

citrus, cotton, sugarcane, and tomato; and that permanent tolerances be established for residues

of trifloxysulfuron {N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(2,2,2-

trifluoroethoxy)-2-pyridinesulfonamide} as follows:

Almond . . . . . . . . . . . . . . . . . . . . 0.02 ppm

Almond, hulls ................ 0.01 ppm

Fruit, citrus, group 10 ......... 0.03 ppm

Cotton, undelinted seed ........ 0.05 ppm

Cotton, gin byproducts . . . . . . . . . 1.0 ppm

Sugarcane . . . . . . . . . . . . . . . . . . . 0.01 ppm

Tomato . . . . . . . . . . . . . . . . . . . . . 0.01 ppm

Currently, the trifloxysulfuron-sodium database is lacking Agency validation of the analytical

method and agreement between the proposed use on cotton and the design of the cotton field
3 of 32

 trials. Additionally, revised Sections B and F of the petition are needed. A listing of the data

gaps associated with Petition 1F06280 can be found in Section 8 of this document.
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N

O

CF3

S

N N

H

N

N OCH3

OCH3

O O

O

Na+

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

TABLE 2.1. Test Compound Nomenclature

Compound

Trifloxysulfuron-sodium

Chemical Structure

Common name Trifloxysulfuron-sodium

Company experimental name CGA-362622

IUPAC name N-[(4,6-dimethoxy-2-pyrimidinyl)carbamoyl]-3-(2,2,2-trifluoroethoxy)-pyridin-2-

sulfonamide sodium salt

CAS name N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(2,2,2-trifluoroethoxy)-2-

pyridinesulfonamide sodium salt

CAS Registry Number 199119-58-9 (sodium salt); 290332-10-4 (sodium salt monohydrate);

145099-21-4 (free sulfonylurea)

End-use product/EP Trifloxysulfuron 75% a.i., wettable granule formulation

Chemical Class Sulfonylurea

Known Impurities of Concern None

TABLE 2.2. Physicochemical Properties

Parameter Value Reference

Molecular Weight Monosodium salt: 459 Daltons

Free acid: 437 Daltons

– 

Melting point/range 173-175 C MRIDs 45371904 and 45371910

pH 7.85 (saturated solution) MRID 45371905

Density 1.63 g/cm3

 at 21 C MRID 45371905

Water solubility (20 C) 63 mg/L at pH 5.06

5016 mg/L at pH 7.04

23.7 g/L at pH 7.71

38 g/L at pH 7.85

MRIDs 45371904 and 45371910

Solvent solubility (temperature not specified) methanol 39 g/L

ethanol 5.6 g/L

isopropanol 0.8 g/L

acetonitrile 5 g/L

acetone 12.4 g/L

ethyl acetate 595 mg/L

MRIDs 45371904 and 45371910

Vapor pressure (25 C) <1 x 10-7 Pa MRIDs 45371904 and 45371910
TABLE 2.2. Physicochemical Properties

Parameter Value Reference

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Dissociation constant, pKa 4.76 (acidic) MRID 45371905

Octanol/water partition coefficient, logPOW

(25 C)

1.4 at pH 5.0

-0.42 at pH 7.0

-1.6 at pH 9.1

MRIDs 45371904 and 45371910

UV/visible absorption spectrum not provided — 

Trifloxysulfuron-sodium is relatively soluble in water at neutral pH, but is significantly

less soluble under acidic conditions, as would be expected given the compound’s pKa value of

4.76 (Table 2.2). Data were not provided regarding solubility in basic solutions; however, based

on the properties summarized in Table 2.2, solubility under basic conditions is expected to be

similar to that in neutral aqueous media. This herbicide has a low vapor pressure at 25 /C and

dissipation via volatilization is not expected under normal conditions.

3.0 HAZARD CHARACTERIZATION

(HIARC Report, TXR No. 0052043, 7/22/03)

3.1 Hazard Profile

The toxicology data base is adequate to support the requested registrations and tolerances

for trifloxysulfuron-sodium and there is high confidence in the hazard endpoints and doseresponse assessments conducted for this chemical. Technical grade trifloxysulfuron-sodium

(CGA 362622) has minimal acute toxicity (Toxicity Category III or IV) and was a non-sensitizer

in dermal sensitization studies.

In subchronic and chronic feeding studies in mice, rats, and dogs, trifloxysulfuronsodium generally caused decreased body weights and body weight gains, often accompanied by

decreased food consumption. Decreased body weights, body weight gains and food

consumption were observed in female mice at the highest dose tested in an 18-month

carcinogenicity study. No other treatment-related effects were observed in male or female mice

at the highest dose tested in this study or in a 3-month feeding study. In a 2-year combined

chronic toxicity/carcinogenicity study in rats, the most sensitive treatment-related effect was

tubular atrophy in the kidneys of females, which developed in the second year of the study. In

the same study at higher doses, Leydig cell hyperplasia of the testes also developed in the second

year in males. In 3-month and/or 28-day subchronic oral studies in rats, the following effects

were also noted: decreased thymus weight and slight hypertrophy of thyroid follicular epithelium

in males and slight histopathology in the liver in females (single cell necrosis, focal necrosis,

inflammation and hepatocellular hypertrophy). In a 28-day dermal study in rats, the only

treatment-related effect was decreased body weight gain in females at the limit dose of 1000

mg/kg/day. No effects were observed in males and no dermal irritation was noted in males or

females. 

In a 1-year chronic toxicity study in dogs, the following treatment-related effects were

observed at the highest dose tested: decreased body weight gain and histopathology in the lungs
6 of 32

of males (gray-white foci and fibrous thickening of the pleura) and increased incidence and

severity of chronic inflammation in the urinary bladder of females. In 3-month and/or 28-day

subchronic oral studies in dogs, the following effects were generally noted in both males and

females: increased mortality (at high doses), clinical signs of toxicity (in moribund dogs),

clinical chemistry changes (suggesting liver toxicity), liver toxicity (histopathological findings,

increased glycogen, increased liver weights), signs of anemia (slight hematological changes with

secondary effects in liver, spleen and bone marrow), and histopathological findings in lungs,

kidney, thyroid, spleen, thymus and testes. 

In the developmental toxicity study in rats at the limit dose, there was a decrease in

maternal food consumption during treatment and a decrease in body weight gain during posttreatment . At the same dose, the offspring had a slight decrease in fetal body weights, an

increase in minimal skeletal findings and an increase in poor/absent skeletal ossification. In the

developmental toxicity study in rabbits, the NOAEL for maternal toxicity was 100 mg/kg/day. 

At a the same dose of 100 mg/kg/day, one fetus had an abnormally shaped heart and at 250

mg/kg/day, three fetuses from two litters had this finding. Historical control data from the

registrant did not describe any fetuses with this observation. In the 2-generation reproduction

study in rats, decreases in body weights, body weight gains and food consumption were observed

in the parental animals. At the same dose, the offspring showed decreases in body weight and

body weight gain, decreases in spleen and thymus weights and an increase in vaginal patency. 

There was no effect on reproduction. There was no evidence of increased quantitative or

qualitative susceptibility in the developmental toxicity study in rats or in the 2-generation

reproduction study in rats. In the developmental toxicity study in rabbits, there was an increase

in quantitative susceptibility based upon the presence of abnormally shaped heart in one fetus at

100 mg/kg/day. Three additional fetuses from two litters at 250 mg/kg/day also had abnormally

shaped hearts. The degree of concern for this finding was low beause there was a clear NOAEL

for this effect, only 1 fetus had the effect at the LOAEL, and the effect was used as a

toxicological endpoint in appropriate risk assessments. There are no residual uncertainties for

pre-natal and/or post-natal toxicity.

In two acute neurotoxicity studies in rats, decreased motor activity was observed at the

limit dose of 2000 mg/kg (only dose tested) in males and females on day 1 in the first study and

only in females in the second study. A NOAEL of 600 mg/kg was established for this effect in

females. Microscopic examination revealed lesions in the nervous system of 2 males and 1

female at the dose of 2000 mg/kg in the first study. Microscopic examination of nervous system

tissues was not performed in the second study. In a subchronic neurotoxicity study in rats, no

neurologic effects were observed in either the males or females. In a 90-day feeding study and

in a 28-day feeding study in dogs, clinical signs of toxicity (including neurotoxic signs) were

observed at high doses, but only in moribund dogs that subsequently died or were sacrificed in

extremis. In none of the other toxicity studies on trifloxysulfuron-sodium was there any

evidence of treatment-related neurotoxicity. Overall, there is not a concern for neurotoxicity

resulting from exposure to trifloxysulfuron-sodium and a developmental neurotoxicity study in

rats is not required. 
7 of 32

In carcinogenicity studies in male and female rats and in male and female mice,

trifloxysulfuron-sodium did not demonstrate any biologically significant evidence of

carcinogenic potential. Trifloxysulfuron-sodium is classified as “not likely to be carcinogenic to

humans” according to the July 2, 1999 EPA Draft Proposed Guidelines for Carcinogen Risk

Assessment.

Technical grade trifloxysulfuron-sodium did not demonstrate any mutagenic potential in

a battery of 5 mutagenicity studies. There is not a concern for mutagenicity resulting from

exposure to trifloxysulfuron-sodium. Results were negative without and with rat S-9 activation

in a reverse gene mutation study using Salmonella typhimurium/Escherichia coli and in a

forward gene mutation study using CHO cells at the HGPRT locus. In an in vitro chromosomal

aberration study in CHO cells, trifloxysulfuron-sodium was negative when tested without and

with rat S-9 activation. In an in vivo micronucleus study in mice using bone marrow cells, the

results were negative and in an in vitro unscheduled DNA synthesis assay in primary rat

hepatocyte cultures, results also were negative.

In metabolism studies in rats, trifloxysulfuron-sodium was rapidly and nearly completely

absorbed and excreted within 48 hours. Urinary excretion was the primary route of elimination. 

Females excreted more of the administered dose (AD) in the urine than did males. There was no

evidence for an enterohepatic circulation. Less than 0.30% of the AD remained in the tissues

after 168 hours. Unchanged parent was eliminated almost entirely in the urine. Females

excreted more unchanged parent in the urine than did males. With the exception of unchanged

parent, the metabolite profile was similar between urine and feces. The primary metabolites in

both urine and feces in all treated groups were Metabolites J (desmethyl parent) and K (5'-

hydroxypyrimidine of parent). Other major metabolites included Metabolites F (formed from

hydroxylation of the parent at the 5' position), X and N (glucuronide conjugates of F), A and D

(additional desmethyl moieties). Several minor metabolites were also identified.

Table 3.1. Acute Toxicity Profile - Trifloxysulfuron-sodium

Test

Material

GDLN Study Type MRID Results

Tox

Category

Technical 870.1100 Acute Oral - rat 45371922 LD50 > 5000 mg/kg IV

Technical 870.1100 Acute Oral - mouse 45371923 LD50 > 5000 mg/kg IV

Technical 870.1200 Acute Dermal - rat 45371925 LD50 > 2000 mg/kg III

Technical 870.1300 Acute Inhalation 45371927 LC50 (M & F): > 5.03 mg/L IV

Technical 870.2400 Primary Eye Irritation 45371929 Moderate irritation to the eye III

Technical 870.2500 Primary Dermal

Irritation

45371931 Mild irritation to the skin IV

Technical 870.2600 Dermal Sensitization

(Buehler)

45371933 Negative N/A

Technical 870.2600 Dermal Sensitization

(Maximization)

45371934 Negative N/A
8 of 32

Table 3.2. Toxicity Profile of Trifloxysulfuron-sodium Technical Grade Active Ingredient.

Guideline

No.

Study Type Results

870.3100 90-Day oral toxicity

rodents (rats)

NOAEL: 507/549 mg/kg/day (M/F)

LOAEL: 1052/1128 mg/kg/day (M/F): M = decreased body weight,

decreased body weight gain, equivocal increased testicular atrophy at end

of recovery phase; F = decreased body weight, decreased body weight

gain, equivocal slightly increased histopathology in liver (single cell

necrosis, focal necrosis, inflammation, hepatocellular hypertrophy).

870.3100 90-Day oral toxicity

rodents (mice)

NOAEL: 1023/1507 mg/kg/day (M/F)

LOAEL: >1023/>1507 mg/kg/day (M/F): M = not attained; F = not

attained

870.3150 90-Day oral toxicity in

nonrodents (dogs)

NOAEL:19.8/19.6 mg/kg/day (M/F)

LOAEL: 164.2/167.3 mg/kg/day (M/F): M = decreased body weight

gain (20%), slight hematological effects, clinical chemistry changes

suggesting hepatotoxicity, decreased thymus weight, thymic atrophy,

increased glycogen in liver, hemorrhage in mesenteric lymph nodes; F =

decreased body weight gain (44%), anemia with extramedullary

hematopoiesis in liver/spleen and myeloid hyperplasia in bone marrow,

clinical chemistry changes suggesting hepatotoxicity, decrease thymus

weight, thymic atrophy and hyaline tubular change in kidney.

870.3200 21/28-Day dermal

toxicity (rats)

NOAEL: 1000/100 mg/kg/day (M/F)

LOAEL: >1000/1000 mg/kg/day(M/F): M = not attained; F = decreased

body weight gain.

No dermal irritation M/F.

870.3700 Prenatal developmental

in rodents (rats)

Maternal NOAEL: 300 mg/kg/day

Maternal LOAEL: 1000 mg/kg/day based on decreased food

consumption during treatment, decreased body weight gain during posttreatment.

Developmental NOAEL: 300 mg/kg/day

Developmental LOAEL: 1000 mg/kg/day based on slight decrease in

fetal weight, increased skeletal anomalies, increased poor/absent skeletal

ossification.

870.3700 Prenatal developmental

in nonrodents (rabbit)

Maternal NOAEL: 100 mg/kg/day

Maternal LOAEL: 250 mg/kg/day based on increased mortality,

increased vaginal/anal bleeding.

Developmental NOAEL: 50 mg/kg/day 

Developmental LOAEL: 100 mg/kg/day based on abnormally shaped

heart (one fetus at 100 mg/kg/day and 3 fetuses from 2 litters at 250

mg/kg/day).

870.3800 Reproduction and

fertility effects (rat)

Parental systemic NOAEL:78.8/83.5 mg/kg/day (M/F)

Parental systemic LOAEL:631/676 mg/kg/day (M/F) based on

decreased body weight and gain as well as decreased food consumption.

Offspring systemic NOAEL:78.8/83.5 mg/kg/day (M/F)

Offspring systemic LOAEL: 631/676 mg/kg/day (M/F):decreased pup

weight and weight gain, decreased spleen weight, thymus weight and

increased vaginal patency.

Reproductive NOAEL:968/1030 mg/kg/day (M/F)

Reproductive LOAEL:>968/1030 (M/F)

870.4100a Chronic toxicity rodents

(rat)

See 870.4300

870.4100 Chronic toxicity dogs NOAEL: 51.1/45.3 mg/kg/day (M/F)

LOAEL: 123/121 mg/kg/day (M/F): M = gray-white foci in lungs,
Table 3.2. Toxicity Profile of Trifloxysulfuron-sodium Technical Grade Active Ingredient.

Guideline

No.

Study Type Results

9 of 32

fibrous thickening of lung pleura, equivocal decreased body weight gain;

F = equivocal increased incidence and severity of chronic urinary bladder

inflammation. 

870.4200 Carcinogenicity rats See 870.4300

870.4200 Carcinogenicity mice NOAEL:854/112 mg/kg/day (M/F)

LOAEL:>854/818 mg/kg/day (M/F): M = not determined; F = decreased

body weight, body weight gain and food consumption. Negative for

carcinogenicity in M and F.

870.4300 Chronic

feeding/Carcinogenicity

rats

NOAEL: 82.6/23.7 mg/kg/day (M/F)

LOAEL: 429/99.3 mg/kg/day (M/F): M = decreased body weight and

gains, decreased food consumption and increased Leydig cell hyperplasia

in testes; F = increased tubular atrophy in kidneys. At 500 mg/kg/day

decreased body weight, body weight gain, food consumption and

increased tubular atrophy in kidneys. Negative for carcinogenicity in M

and F.

870.5100 Gene Mutation bacterial

reverse mutation assay

(S. typhimurium/E. coli)

Negative without and with S-9 activation.

870.5300 In vitro mammalian cell

forward gene mutation

assay (CHO

cells/HGPRT locus)

Negative without and with S-9 activation.

870.5375 In vitro mammalian

cytogenetics assay in

CHO cells

Negative without and with S-9 activation.

870.5395 Cytogenetics -

mammalian erythrocyte

micronucleus test in the

mouse

Negative at single oral doses up to 5000 mg/kg.

870.5500 In vitro unscheduled

DNA synthesis (primary

rat hepatocytes)

Negative response up to 250 μg/mL. Cytotoxicity at $15.63 μg/mL.

870.6200 Acute neurotoxicity

screening battery (rat)

NOAEL:<2000 mg/kg/day (M/F)

LOAEL: 2000 mg/kg/day (M/F): M&F = decreased motor activity on

day 1, histopathological lesions in nervous system tissues. 

870.6200 Acute neurotoxicity

screening battery (rat)

NOAEL: 2000/600 mg/kg/day (M/F)

LOAEL: > 2000/2000 mg/kg/day (M/F): M = not attained; F =

decreased motor activity on day 1

870.6200 Subchronic

neurotoxicity screening

battery (rat)

NOAEL:112/553 mg/kg/day (M/F)

LOAEL:472/1128 mg/kg/day (M/F): M = decreased body weight, body

weight gain and food consumption.; F = decreased body weight.

870.6300 Developmental

neurotoxicity (rat)

No study performed.

870.7485 Metabolism and

pharmacokinetics (rat)

Rapidly absorbed and exceted. Most (>87%) of the administered dose

(AD) was excreted within 24 hours. After 7 days, very little (#0.3% of

AD) remained in the tissues. Urine was the primary route of excretion

in males (50-61% of AD) and in females (70-80% of AD). Unchanged

parent in males (11-20% of AD) and in females (37-47% of AD) was

excreted almost entirely in the urine and only trace amounts were found

in the feces. With the exception of the parent, the metabolite profile was

similar between the urine and feces. The 2 primary metabolites in both
Table 3.2. Toxicity Profile of Trifloxysulfuron-sodium Technical Grade Active Ingredient.

Guideline

No.

Study Type Results

10 of 32

urine and feces were Metabolite J (desmethyl parent, up to 26% of AD)

and Metabolite K (5'hydroxy-pyrimidine of parent, up to 19% of AD). 

Other metabolites were Metabolites X, N, F, A and D, each up to 8.2% of

the AD in males and up to 4.7% of the AD in females. Several minor

metabolites were also identified as Metabolite Q, Metabolite P,

guanidine, CGA-382997 and CGA-368732 (each #4.4% of the AD).

870.7485 Biliary Metabolism (rat) In bile duct cannulated rats, absorption was 84-88% of the Administered

Dose (AD) at 48 hours. Nearly all of the AD was excreted within 48

hours. Excretion in urine ranged from 58-76%, in bile from 5-27%, and

in feces was about 6% of the AD. There was no evidence for an

enterohepatic circulation. Biotransformation was similar to that in the

conventional rat metabolism study. The metabolite profiles in urine, bile

fluid and feces were all similar.

870.7600 Dermal Penetration (rat) No study performed.

3.2 FQPA Considerations

The HIARC met on July 1, 2003 to evaluate the potential for increased susceptibility of

infants and children resulting from exposure to trifloxysulfuron-sodium according to the

February 2002 OPP 10X Guidance Document. The HIARC concluded that the toxicological

data base for trifloxysulfuron-sodium is complete for FQPA purposes. A complete complement

of acceptable developmental, reproduction and mammalian neurotoxicity studies is available. 

Based on an evaluation of the hazard data, the HIARC indicated that the Special FQPA Safety

Factor may be reduced to 1x. The Trifloxysulfuron-sodium Risk Assessment Team subsequently

evaluated the quality and completeness of the exposure data, and, based on a weight-of-theevidence consideration of all the available data, recommended that the Special FQPA Safety

Factor be reduced to 1x. This recommendation was based on the following: 

C The toxicological data base is complete for FQPA assessment. 

C There was no evidence of increased quantitative or qualitative susceptibility in the

developmental toxicity study in rats. At the limit dose, maternal effects were

decreased food consumption during treatment and decreased body weight gain

during post-treatment. The only fetal findings noted at the limit dose were a slight

decrease in fetal body weights, an increase in minimal skeletal findings and

poor/absent skeletal ossification. 

C There was evidence of increased quantitative susceptibility in the developmental

toxicity study in rabbits. The maternal NOAEL was 100 mg/kg/day based on

increased mortality and increased vaginal/anal bleeding at the LOAEL of 250

mg/kg/day. The developmental NOAEL was 50 mg/kg/day based on an increased

incidence of abnormally shaped hearts at the LOAEL of 100 mg/kg/day (one fetus

at 100 mg/kg/day). Three additional fetuses from two litters at 250 mg/kg/day

also had abnormally shaped hearts. In historical control data provided by the

registrant, there were no reported instances of abnormally shaped hearts. The

degree of concern is low for the quantitative evidence of susceptibility seen in the
11 of 32

rabbit developmental study because there was a clear NOAEL for this effect, only

one fetus had the effect at the LOAEL, and the effect was used as a toxicological

endpoint in appropriate risk assessments.

C There was no evidence of increased quantitative or qualitative susceptibility in the

2-generation reproduction study in rats.

C There are no residual uncertainties for pre-natal and/or post-natal toxicity.

C A developmental neurotoxicity study in rats is not required.

C The acute and chronic dietary food exposure assessments assumed tolerance level

residue data and 100% crop treated. The acute and chronic risk assessments will

not underestimate exposure or risk since the exposures are based on reliable data

derived from studies designed to produce worst-case residues. 

C The dietary drinking water assessment used concentration values generated by

model and associated modeling parameters which are designed to provide

conservative, health protective, high-end estimates of water concentrations which

will not likely be exceeded. Furthermore, HED assumed that non-parent residues

of concern occur at the highest levels observed in the environmental fate studies. 

This assumption results in overestimated levels of the total residues of concern

since it assumes that all of the compounds occur simultaneously, ignoring the

kinetics of their formation and dissipation.

C The recreational exposure assessment will not underestimate postapplication

exposure to golfers resulting from the use of trifloxysulfuron-sodium on golf

course turf.

3.3 Dose-Response Assessment

For acute dietary exposure for females (13-49 years), the toxicology endpoint was

selected from the developmental toxicity study in rabbits in which the developmental NOAEL

was 50 mg/kg/day and the developmental LOAEL was 100 mg/kg/day based on an increased

incidence of abnormally shaped hearts in fetuses. A conventional Uncertainty Factor (UF) of

100x (10x for interspecies extrapolation and 10x for intraspecies variation) was applied to the

NOAEL to determine the aRfD of 0.5 mg/kg. Application of the Special FQPA Safety Factor of

1 to the aRfD resulted in an aPAD of 0.5 mg/kg. The abnormally shaped hearts observed in this

study are considered to possibly have been induced by a single dose of test material. Since these

anomalies were observed in fetuses, this endpoint is applicable only to the population subgroup

females (13-49 years).

For acute dietary exposure for the general population, the toxicology endpoint was

selected from two acute neurotoxicity studies in rats in which the NOAEL was determined to be

600 mg/kg and the LOAEL to be 2000 mg/kg based on decreased motor activity on Day 1. This

NOAEL of 600 mg/kg is considered to also be protective of the histopathological lesions

described in nervous system tissues of males and females in one of these studies at the LOAEL

of 2000 mg/kg. A conventional UF of 100x was applied to the NOAEL to determine the aRfD

of 6.0 mg/kg. Application of the Special FQPA Safety Factor of 1 to the aRfD resulted in an

aPAD of 6.0 mg/kg. The decreased motor activity and histopathological lesions observed in this

study were induced by a single dose of test material.
12 of 32

For chronic dietary exposure for all population subgroups, the toxicology endpoint was

selected from a combined chronic toxicity/carcinogenicity study in rats in which the NOAEL

was 23.7 mg/kg/day and the LOAEL was 99.3 mg/kg/day based on increased tubular atrophy in

the kidneys of females. A conventional UF of 100x was applied to the NOAEL to determine the

cRfD of 0.237 mg/kg/day. Application of the Special FQPA Safety Factor of 1 to the cRfD

resulted in a cPAD of 0.237 mg/kg/day.

For short-term (1-30 days) incidental oral exposures, the toxicology endpoint was

selected from the 2-generation reproduction study in rats in which the offspring NOAEL was 79

mg/kg/day and the offspring LOAEL was 631 mg/kg/day based on decreased body weights on

day 21. For short-term incidental oral exposures, the Margin of Exposure (MOE) is 100. For

intermediate-term (1-6 months) incidental oral exposures, the toxicology endpoint was selected

from the 1-year chronic feeding study in dogs in which the NOAEL was 45 mg/kg/day and the

LOAEL was 121 mg/kg/day based on decreased body weight gain and histopathology in the

lungs of males and on chronic bladder inflammation in females. The NOAEL of 19.6 mg/kg/day

from the subchronic 90-day feeding study in dogs was not used for intermediate-term oral,

dermal, or inhalation exposures because it is approximately 8-fold lower than the LOAEL of 164

mg/kg/day in this study and is considered to be unrealistically low since a NOAEL of 45

mg/kg/day was determined in the longer-term 1-year chronic feeding study in dogs. For

intermediate-term incidental oral exposures, the Margin of Exposure (MOE) is 100.

For short-term (1-30 days) dermal exposures, the toxicology endpoint was selected from

a 28-day dermal toxicity study in rats in which the systemic NOAEL was 100 mg/kg/day and the

systemic LOAEL was 1000 mg/kg/day based on decreased body weight gain in females. For

short-term inhalation exposures, the toxicology endpoint was selected from the developmental

toxicity study in rabbits in which the developmental NOAEL was 50 mg/kg/day and the

developmental LOAEL was 100 mg/kg/day based on an increased incidence of abnormally

shaped hearts in fetuses. For short-term dermal and inhalation exposures, the target MOE is the

conventional 100. For intermediate-term (1-6 months) dermal and inhalation exposures, the

toxicology endpoint was selected from the 1-year chronic feeding study in dogs in which the

NOAEL was 45 mg/kg/day and the LOAEL was 121 mg/kg/day based on decreased body weight

gain and histopathology in the lungs of males and on chronic bladder inflammation in females. 

For intermediate-term dermal and inhalation exposures, the target MOE is 100. For long-term

(>6 months) dermal and inhalation exposures, the toxicology endpoint was selected from the

combined chronic toxicity/carcinogenicity study in rats in which the NOAEL was 23.7

mg/kg/day and the LOAEL was 99.3 mg/kg/day based on increased tubular atrophy in the

kidneys of females. For long-term dermal and inhalation exposures, the target MOE is 100. For

the intermediate- and long-term dermal exposures, a 30% dermal absorption factor was used

since the toxicology endpoints for both exposures were selected from oral studies. The dermal

absorption factor of 30% was determined based on the high molecular weight of

trifloxysulfuron-sodium, its ionic properties,its solubility characteristics in water and other

solvents, and on the dermal absorption factors of other, closely related sulfonylurea herbicides

[triflusulfuron-methyl, 27% (HIARC Report, 12/5/2001, TXR No. 0050332); and primisulfuronmethyl, 30% (HIARC Report, 4/26/2002, TXR No. 0050694)]. For intermediate-term dermal

exposures, application of the 30% dermal absorption factor to the oral dose of 45 mg/kg/day
13 of 32

from the 1-year chronic feeding study in dogs results in an equivalent dermal dose of 150

mg/kg/day, which is higher than the dermal dose of 100 mg/kg/day used for the short-term

dermal exposure. This difference, however, was determined to be of no practical significance

when performing risk assessments for either exposure scenario, and the discrepancy will not be

resolved at this time. For all the inhalation exposures, a 100% inhalation absorption factor

(default value) was used since the toxicology endpoints for all exposures were selected from oral

studies.

 Trifloxysulfuron-sodium is classified as “not likely to be carcinogenic to humans”

according to the July 2, 1999 EPA Draft Proposed Guidelines for Carcinogen Risk Assessment.

The HIARC recommended that when calculating aggregate exposures and risks, the oral

and dermal routes could be combined since the toxicological effects are the same.

Table 3.3. Summary of Toxicological Doses and Endpoints for Trifloxysulfuron-sodium for Use in

Human Risk Assessments

Exposure

Scenario

Dose Used in Risk

Assessment, UF 

Special FQPA SF* and

Level of Concern for

Risk Assessment

Study and Toxicological Effects

Acute Dietary

(females 13-49)

Developmental

NOAEL = 50

mg/kg/day

UF = 100 

Acute RfD =0.5

mg/kg

FQPA SF = 1

aPAD = 

acute RfD

 FQPA SF

= 0.5 mg/kg

Developmental Toxicity Study in

Rabbits. Developmental LOAEL =

100 mg/kg/day based on increased

incidence of abnormal shaped hearts in

fetuses.

Acute Dietary

(general

population)

NOAEL = 600

mg/kg

UF = 100 

Acute RfD =6.0

mg/kg 

FQPA SF = 1

aPAD = 

acute RfD

 FQPA SF

= 6.0 mg/kg

Acute Neurotoxicity Studies in Rats. 

LOAEL = 2000 mg/kg based on

decreased motor activity on day 1 and

histopathological lesions in nervous

system tissues of males and females. 

Chronic Dietary

(all populations)

NOAEL= 23.7

mg/kg/day

UF = 100

Chronic RfD =

0.237 mg/kg/day

FQPA SF = 1

cPAD = 

chronic RfD

 FQPA SF

= 0.237 mg/kg/day

Combined Chronic Toxicity/

Carcinogenicity Study in Rats.

LOAEL = 99.3 mg/kg/day based on

increased tubular atrophy in the

kidneys of females (developing after

12 months). 

Incidental Oral

Short-Term

(1 - 30 days)

Offspring NOAEL =

78.8/83.5 (M/F)

mg/kg/day

Residential LOC for

MOE = 100

Occupational = NA

2-Generation Reproduction Study in

Rats. Offspring LOAEL = 631/676

(M/F) mg/kg/day based on decreased

pup body weights on day 21.

Incidental Oral

Intermediate-Term

(1 - 6 months)

NOAEL = 51.1/45.3

(M/F) mg/kg/day

Residential LOC for

MOE = 100

Occupational = NA

1-Year Chronic Feeding Study in

Dogs. LOAEL = 123/121 (M/F)

mg/kg/day based on decreased body

weight gain and histopathology in

lungs in males and chronic urinary

bladder inflammation in females. 
Table 3.3. Summary of Toxicological Doses and Endpoints for Trifloxysulfuron-sodium for Use in

Human Risk Assessments

Exposure

Scenario

Dose Used in Risk

Assessment, UF 

Special FQPA SF* and

Level of Concern for

Risk Assessment

Study and Toxicological Effects

14 of 32

Dermal 

Short-Term

(1 - 30 days)

Dermal study

Systemic NOAEL=

100 mg/kg/day

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100 

28-Day Dermal Toxicity Study in

Rats. Systemic LOAEL = 1000

mg/kg/day based on decreased body

weight gain in females. We note that

the short-term dermal NOAEL is

lower than the “equivalent” NOAEL

chosen for intermediate-term dermal

assessments; however, the endpoint

will not be revised at this time.

Dermal 

Intermediate-Term

(1 - 6 months)

Oral study NOAEL=

51.1/45.3 (M/F) 

mg/kg/day

(dermal absorption

factor = 30%)

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100 

1 Year Chronic Feeding Study in

Dogs. LOAEL = 123/121 (M/F)

mg/kg/day based on decreased body

weight gain and histopathology in

lungs in males and chronic urinary

bladder inflammation in females. 

Dermal 

Long-Term

(> 6 months)

Oral study NOAEL=

23.7 mg/kg/day

(dermal absorption

factor = 30%)

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100

Combined Chronic Toxicity/

Carcinogenicity Study in Rats.

LOAEL = 99.3 mg/kg/day based on

increased tubular atrophy in the

kidneys of females (developing after

12 months).

Inhalation 

Short-Term

(1 - 30 days)

Oral study NOAEL=

50 mg/kg/day

(inhalation 

absorption factor =

100%)

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100 

Developmental Toxicity Study in

Rabbits. LOAEL = 100 mg/kg/day

based on increased incidence of

abnormal shaped hearts in fetuses.

Inhalation 

Intermediate-Term

(1 - 6 months)

Oral study NOAEL=

51.1/45.3 (M/F) 

mg/kg/day

(inhalation 

absorption factor =

100%)

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100 

1-Year Chronic Feeding Study in

Dogs. LOAEL = 123/121 (M/F)

mg/kg/day based on decreased body

weight gain and histopathology in

lungs in males and chronic urinary

bladder inflammation in females. 

Inhalation 

Long-Term

(> 6 months)

Oral study NOAEL=

23.7 mg/kg/day

(inhalation

absorption factor =

100%)

Residential LOC for

MOE = 100

Occupational LOC for

MOE = 100

Combined Chronic Toxicity/

Carcinogenicity Study in Rats.

LOAEL = 99.3 mg/kg/day based on

increased tubular atrophy in the

kidneys of females (developing after

12 months).

Cancer (oral,

dermal, inhalation)

Classification: Not Likely to be carcinogenic to humans

UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level,

LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD =

reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable

3.4 Endocrine Disruption
15 of 32

EPA is required under the FFDCA, as amended by FQPA, to develop a screening

program to determine whether certain substances (including all pesticide active and other

ingredients) “may have an effect in humans that is similar to an effect produced by a naturally

occurring estrogen, or other such endocrine effects as the Administrator may designate.” 

Following recommendations of its Endocrine Disruptor and Testing Advisory Committee

(EDSTAC), EPA determined that there was a scientific basis for including, as part of the

program, the androgen and thyroid hormone systems, in addition to the estrogen hormone

system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of

potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that

effects in wildlife may help determine whether a substance may have an effect in humans,

FFDCA authority to require the wildlife evaluations. As the science develops and resources

allow, screening of additional hormone systems may be added to the Endocrine Disruptor

Screening Program (EDSP). In the available toxicity studies on trifloxysulfuron-sodium, there

was no toxicologically significant evidence of endocrine disruptor effects. When additional

appropriate screening and/or testing protocols being considered under the Agency’s EDSP have

been developed, trifloxysulfuron-sodium may be subjected to further screening and/or testing to

better characterize effects related to endocrine disruption. 

4.0 EXPOSURE ASSESSMENT

4.1 Summary of Proposed Uses

Trifloxysulfuron-sodium is a low-application-rate herbicide belonging to the sulfonylurea

class of chemicals. Like other herbicides in this class, trifloxysulfuron-sodium acts by inhibiting

the plant enzyme acetolactate synthase, resulting in reduced production of branched-chain amino

acids. The leaves of susceptible plants typically turn yellow, red, or purple several days after

application. Complete plant death occurs 1-3 weeks after application, depending on the species

and environmental conditions. Trifloxysulfuron-sodium is being proposed for use on almonds,

citrus, cotton, sugarcane, tomatoes, and turf. In conjunction with the subject tolerance petition,

Syngenta has submitted an application for Section 3 registration of a 75% water-dispersible

granule (WG) formulation (Trifloxysulfuron-Sodium 75WG Herbicide; EPA File Symbol

100-RRGE) for postemergence use, by ground equipment only, on almonds, citrus, cotton

(picker varieties only), sugarcane, and tomatoes (transplanted tomatoes in FL only). The 75%

WG formulation is to be applied at maximum seasonal rates ranging from 0.014 lb ai/A for

tomatoes to 0.080 lb ai/A for turf. Pre-harvest intervals on the proposed labels range from 3

days for almond to 100 days for sugarcane. Rotational crop restrictions range from 2 months to

12 months, depending on the target crop and the rotational crop. These restrictions appear to be

based on phytotoxicity, rather than residue chemistry, concerns. More details regarding the

proposed uses are presented in Table 4.1.
16 of 32

Table 4.1. Summary of Directions for Use of Trifloxysulfuron-Sodium (75% WG formulation, EPA File

Symbol 100-RRGE).

Applic. Timing,

Type, and Equip.

Applic.

Rate

(lb ai/A)

Max. No.

Applic. per

Season

Max. Seasonal

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and Limitations

Almond

Postemergence

Directed to soil

Ground Equip.

0.019 3 0.056 3 For use as a tank mix with glyphosate

formulations registered for use on almonds. 

The minimum retreatment interval is 30

days. Application to newly established

groves (<2 years old) is prohibited.

Citrus

Postemergence

Directed to soil

Ground Equip.

0.019 3 0.056 14 For use as a tank mix with glyphosate

formulations registered for use on citrus. 

The minimum retreatment interval is 30

days. Application to newly established

groves (<2 years old) is prohibited.

Cotton (picker varieties only)

Early 

postemergence

Over-the-top

(minimum of 5 true

leaves)

Ground Equip.

0.005-

0.007

Not

specified

(NS)

0.019 60 Use limited to AL, AR, FL, GA, LA, MS,

NC, SC, TN, VA, the boot heel area of MO

and portions of OK and TX, excluding the

high plains region of West TX and OK. 

Tank mixing with any other herbicides or

additives (other than surfactant) or with

insecticides containing malathion,

profenofos, or emamectin benzoate is

prohibited.

Postemergence ($8

inches in height to

layby)

Directed spray

Ground Equip.

0.007-

0.012

NS 0.019 60 Use limited to AL, AR, AZ, CA, FL, GA,

LA, MS, NC, SC, TN, VA, the boot heel

area of MO and portions of OK and TX,

excluding the high plains region of West

TX and OK. The minimum retreatment

interval is 14 days. Applications are to be

directed to minimize contact with cotton

leaves. Applications may be made alone or

as a tank mix with glyphosate (to Roundup

Ready® cotton varieties only), Caparol®

(prometryn), Dual Magnum®

(metolachlor), MSMA, Staple®

(pyrithiobac-sodium), Cotoran®

(fluometuron), or Buctril® (bromoxynil,

BXN cotton varieties only). Tank mixing

with insecticides containing malathion,

profenofos, or emamectin benzoate is

prohibited.

Sugarcane

Early

 postemergence (up

to 24" tall)

Over-the-top

Ground Equip.

0.014 3 0.070 100 Use limited to FL, LA, and TX on ratoon

sugarcane only. The minimum retreatment

interval is 14 days. Applications may be

made alone or as a tank mix with atrazine

or asulam.
Table 4.1. Summary of Directions for Use of Trifloxysulfuron-Sodium (75% WG formulation, EPA File

Symbol 100-RRGE).

Applic. Timing,

Type, and Equip.

Applic.

Rate

(lb ai/A)

Max. No.

Applic. per

Season

Max. Seasonal

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and Limitations

17 of 32

Postemergence (18"

tall up to layby)

Directed spray

Ground Equip.

0.014-

0.028

3 0.070 100 Use limited to FL, LA, and TX on plant or

ratoon sugarcane. The minimum

retreatment interval is 14 days. 

Applications may be made alone or as a

tank mix with atrazine or asulam.

Tomato (transplanted tomatoes in FL only)

Preemergence (pretransplant)

Ground

0.007 1 

(+ 1 postemergence)

0.014 45 Use limited to FL. Mechanical

incorporation of product into the soil is to

be avoided.

Postemergence

Over-the-top or

directed

Ground Equip.

0.007-

0.014

1

(+1 preemergence)

0.014 45 Use limited to FL. Application is to be

made prior to fruit set.

Turf

Postemergence

Broadcast

Ground Equip.

0.005 -

0.026

Not

specified; 3

implied

0.080 N/A 12-month rotational restriction to anything

other than turf grasses. Via

communication with the petitioner, turf

uses are to be restricted to golf courses

only.

4.2 Dietary Exposure/Risk Pathway

4.2.1 Residue Profile

(M. Doherty, D284480, 8/25/03; MARC Report, TXR No. 0052100, 8/25/03)

The nature of the residues in plants and animals is adequately understood; the terminal

residue of concern in plants and animals is trifloxysulfuron. In water, residues of concern

include trifloxysulfuron as well as the metabolites CGA-053052, CGA-382997, and CGA368732 (see Section 4.3 for more details). Trifloxysulfuron-sodium was found to be extensively

metabolized in plants. The leaves/foliage of plants were found to have the highest residues, with

very low residues in the edible portions of the crops. Trifloxysulfuron-sodium was found to be

less extensively metabolized in livestock, although similar metabolites were found. 

The available analytical methodology is tentatively considered to be adequate for

tolerance enforcement, pending completion of a successful tolerance method validation (TMV). 

The limit of quantitation (LOQ) is 0.01 ppm for each plant substrate. Multiresidue methods

currently in use by the FDA are not successful at extracting or quantitating residues of

trifloxysulfuron-sodium.

Adequate field trial data are available for sugarcane, citrus, almond, and tomato. In

samples from all of these trials, residues of trifloxysulfuron were < 0.01 ppm. HED notes that
18 of 32

the sugarcane residue data are not supported by adequate storage stability data (#21-month

storage of field trial sample vs. 9-month storage stability data). However, in the sugarcane

metabolism study, which was conducted at 10 times the maximum proposed application rate,

total radioactive residues (TRR) were <0.001 ppm in mature sugarcane. Therefore, further

storage stability data for sugarcane will not be required. Apparent residues of trifloxysulfuron

were found in some control samples of almond, citrus, and sugarcane at levels in excess of 20%

of the LOQ. Therefore, HED is recommending that the proposed tolerances be raised to levels

above the LOQ for those commodities (see below). Cotton field trial data were submitted from

studies conducted at three times the maximum proposed use rate on cotton. Under those

conditions, quantifiable residues were found in 2 out of 38 samples of cottonseed (0.039 ppm

max.) and in 7 out of 12 samples of cotton gin byproducts (0.090 ppm max.). These data are

acceptable for a conditional registration.

Processing studies were submitted for cotton, orange, and sugarcane and showed no

concentration of trifloxysulfuron in any processed commodities derived from these raw

agricultural commodities (RACs). A tomato processing study is not required for this herbicide

based on field trials conducted at a 5X exaggerated rate that showed nonquantifiable residues of

trifloxysulfuron in tomato.

Based on the results of the livestock metabolism studies and on the anticipated dietary

burdens to livestock, there is no expectation of finite residues of trifloxysulfuron in livestock

matrices [i.e., 40 CFR 180.6(a)(3)]. Livestock feeding studies have not been submitted for

trifloxysulfuron and none are required at this time.

Confined rotational crop and field rotational crop studies showed residues of

trifloxysulfuron to be < 0.01 ppm in all matrices. There is a storage stability data gap associated

with the field rotational crop data; however, since the confined rotational crop study does not

indicate the need for a field study, supporting storage stability data are not required. The label

lists a number of rotational crop restrictions which are, presumably, in place due to phytotoxicity

concerns.

At present, there are no Canadian, Mexical, or Codex maximum residue limits (MRLs)

and international harmonization is not an issue with the proposed uses.

Based on the available data, HED is recommending that the following permanent

tolerances be established for residues of trifloxysulfuron in/on:

Almond . . . . . . . . . . . . . . . . . . . . 0.02 ppm

Almond, hulls ................ 0.01 ppm

Fruit, citrus, group 10 ......... 0.03 ppm

Cotton, undelinted seed ........ 0.05 ppm

Cotton, gin by-products . . . . . . . . 1.0 ppm

Sugarcane . . . . . . . . . . . . . . . . . . . 0.01 ppm

Tomato . . . . . . . . . . . . . . . . . . . . . 0.01 ppm
19 of 32

4.2.2 Acute and Chronic Dietary Exposure and Risk

(M. Doherty, D293086, 8/25/03)

Acute and chronic dietary risk assessments were conducted in order to support the fooduse Section 3 registration requests for the new herbicide trifloxysulfuron-sodium on almonds,

citrus, cotton, sugarcane, and tomatoes. Exposure estimates were obtained from the Dietary

Exposure Evaluation Model (DEEM-FCID, Version 1.30), which uses food consumption data

from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996

and 1998. The analyses include the highly conservative assumptions that all crops from the

requested uses are treated with trifloxysulfuron-sodium and that residues of the herbicide are at

tolerance levels. Based on these assumptions, acute and chronic risk estimates for all of the

examined population subgroups (including women of childbearing age, infants, and children) 

are less than 1% of the population-adjusted doses (Table 4.2) and are below HED’s level of

concern (100% of the population-adjusted doses).
20 of 32

Table 4.2. Summary of Dietary Exposure and Risk for Trifloxysulfuron-sodium.

Population

Subgroup a

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

aPAD,

mg/kg

Exposure, 

mg/kg/day b

%

aPAD

cPAD, 

mg/kg/day

 Exposure, 

mg/kg/day b

%

cPAD

Dietary

Exposure,

mg/kg/day

Risk

General U.S.

Population

6.0 0.00024 < 1 0.237 0.000057 < 1 Not Applicable

All Infants (< 1

year old)

6.0 0.00010 < 1 0.237 0.000028 < 1

N/A N/A

Children 1-2

years old

6.0 0.00074 < 1 0.237 0.000170 < 1

Children 3-5

years old

6.0 0.00055 < 1 0.237 0.000142 < 1

Children 6-12

years old

6.0 0.00036 < 1 0.237 0.000090 < 1

Youth 13-19

years old

6.0 0.00026 < 1 0.237 0.000058 < 1

Adults 20-49

years old

6.0 0.00018 < 1 0.237 0.000042 < 1

Adults 50+ years

old

6.0 0.00015 < 1 0.237 0.000042 < 1

Females 13-49

years old

0.5 0.00020 < 1 0.237 0.000044 < 1

a The values for the population with the highest risk for each type of risk assessment are bolded. b Reported to 2 significant figures.

4.3 Water Exposure/Risk Pathway

(S. Termes, D276988, 8/20/03)

Trifloxysulfuron-sodium is a new chemical for which no drinking water monitoring data

are available. Therefore, the water resource assessments are based solely on model-estimated

exposure concentrations. Estimates were only performed for parent trifloxysulfuron-sodium. 

Exposure concentrations for the water resources assessments were estimated for uses on

almonds, citrus, cotton, sugar cane, tomato, and turf. The application rates, frequency and

number of applications vary between crops and were taken from the proposed labels for products

containing trifloxysulfuron as the active ingredient. There are no aerial applications permitted

for this chemical. 

In estimating residues of trifloxysulfuron-sodium in water, the highest application rates,

frequency, number and shortest application interval were selected to represent the use pattern

that would represent the high-end of possible exposure. The turf use has the highest seasonal

application rate (0.080 lb ai/A) and sugarcane has the highest per application rate (0.028 lb ai/A). 

Tomato use has the lowest seasonal application rate (0.014 lb ai/A) and fewest applications (2).

Trifloxysulfuron-sodium can be applied up to three times for the other uses. It was assumed that

all applications were made by ground spray to soil, except for turf, where a ground spray to
21 of 32

foliage was considered. The sugarcane use pattern was used to model residues in water.

The residues of concern in drinking water are parent trifloxysulfuron, CGA-053052,

CGA-382997, and CGA-368732. In order to account for the potential residues of these

breakdown products in water, HED has assumed that these metabolites occur at the maximum

percent of the applied parent compound observed in 14C-environmental fate studies. Those

values are 61% of the a.i. for CGA-053052 (hydrolysis at pH 5 after 30 days), 54% of the a.i. for

CGA-382997 (aerobic soil metabolism after 365 days), and 53% of the a.i. for CGA-368732

(hydrolysis at pH 7 after 30 days). The conversion factor to go from parent compound to all

residues of concern is, therefore, 2.68. This assumption results in overestimated levels of the

total residues of concern since it assumes that all of the compounds occur simultaneously,

ignoring the kinetics of their formation and dissipation. These total-residue estimated

environmental concentrations (EECs) are compared to aggregated exposure estimates (Section 5)

to characterize the likelihood of aggregate risk exceeding HED’s levels of concern. Given that

the EECs for surface water are greater than those for ground water, the surface water values are

used in the aggregate assessment.

Table 4.3. Summary of Estimated Surface and Ground Water Concentrations for Trifloxysulfuron-sodium

and Associated Residues of Concern.

Exposure Duration Trifloxysulfuron-sodium Trifloxysulfuron-sodium + CGA-053052 + 

CGA-382997 + CGA-368732 a

Surface Water

Conc., ppb b

Ground Water

Conc., ppb c

Surface Water

Conc., ppb

Ground Water

Conc., ppb

Acute 3.83 0.032 10.26 0.086

Chronic (non-cancer) 0.31 0.032 0.83 0.086

a Assumes worst-case factors, relative to trifloxysulfuron-sodium, of 0.61 for CGA-053052, 0.54 for CGA382997,

and 0.53 for CGA-368732; as provided in the MARC Report (TXR No. 0052100, 8/25/03). The conversion factor

for trifloxysulfuron-sodium to all residues of concern is 2.68.

b From the Tier II PRZM-EXAMS - Index Reservoir model. Input parameters are based on sugarcane grown in

Florida.

c From the SCI-GROW model assuming a maximum seasonal use rate of 0.0788 lb ai/A, a Koc of 29, and a half-live

of 29.84 days.

4.4 Residential Exposure/Risk Pathway

(S. Wang, D284482, 9/20/03)

4.4.1 Home Uses

It is HED’s understanding, from communications with the petitioner, that the proposed

turf use for trifloxysulfuron-sodium will be limited to golf courses only (See Section 4.4.2,

below). Therefore, there are no home uses for trifloxysulfuron-sodium being proposed at this

time and a residential exposure/risk assessment is not required. HED recommends that “for use

on golf courses only” be included in the turf label. 

4.4.2 Recreational
22 of 32

HED has examined the potential postapplication exposure to individuals over 12 years of

age from the proposed use of trifloxysulfuron-sodium on golf courses. Duration of such

exposure is anticipated to be short-term. The short-term dermal post-application exposure for

golfing was estimated to be 0.005 mg/kg/day. The estimate assumes that 18 holes of golf are

played in 4 hours, that there are 0.015 :g ai/cm2 of turf, that the transfer coefficient for turf is

500 cm2/hour, and that the average golfer weighs 60 kg (standard risk assessment weight for

women and youth). The frequency and duration for the golfer exposure were based on

information published in the 1992 Golf Course Operations: Cost of Doing Business/Profitability

(The Center for Golf Course Management. Library of Congress GV975.G56 1992.). Transfer

coefficients are based on surrogate data, from chlorothalonil and chlorpyrifos, describing actual,

median-value exposures to golfers. Applying the short-term dermal NOAEL of 100 mg/kg/day

results in a MOE for golfing of 200,000. This is well above the above the target Margin of

exposure (MOE) of 100 and therefore considered to be safe.

The vapor pressure of trifloxysulfuron-sodium is very low (<1×10-7 Pa, see Table 2.2)

and, therefore, inhalation exposure to trifloxysulfuron-sodium vapor is not expected to occur. 

HED has not assessed inhalation exposure to trifloxysulfuron-sodium due to recreational

activities.

4.4.3 Other (Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby to spraying

operations. This is particularly the case with aerial application, but, to a lesser extent, could also

be a potential source of exposure from the ground application method employed for

trifloxysulfuron-sodium. The Agency has been working with the Spray Drift Task Force, EPA

Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop

the best spray drift management practices. The Agency is now requiring interim mitigation

measures for aerial applications that must be placed on product labels/labeling. The Agency has

completed its evaluation of the new data base submitted by the Spray Drift Task Force, a

membership of U.S. pesticide registrants, and is developing a policy on how to appropriately

apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied

by air, orchard airblast and ground hydraulic methods. After the policy is in place, the Agency

may impose further refinements in spray drift management practices to reduce off-target drift

and risks associated with aerial as well as other application types where appropriate.

5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION

In assessing aggregate risks, HED has considered exposures from dietary (food and

drinking water) and non-dietary (dermal and inhalation) pathways. For the dietary pathway,

food exposure estimates come from the dietary exposure analysis discussed above (Section

4.2.2). Sufficient monitoring data for trifloxysulfuron are not available to include drinking water

as a quantifiable pathway of exposure. Therefore, HED has calculated drinking water levels of

comparison (DWLOCs) as a means of assessing whether or not aggregate exposures to

trifloxysulfuron are likely to exceed our levels of concern. The DWLOCs represent the

concentrations of a pesticide in surface or ground water below which there is reasonable
23 of 32

Risk Quotient RQ Estimated Exposure Target MOE

NOAEL ( ) = ×

(1)

Max Allowable Drinking Water Exposure MADWE ARQ ( ) NOAEL

Target MOE Oral Dietary or Non dietary

. ()

( )

=− ×





 





−

1 (3)

DWLOC

MADWE 1000 g

mg Body Weight

Water Consumption =

× μ × (4)

certainty that no adverse health effects will occur, in light of other, non-drinking-water pathways

of exposure. The DWLOCs are compared to the EECs (See Section 4.3) to determine if

aggregate risks are likely to exceed our level of concern. For non-dietary pathways relevant to

trifloxysulfruon-sodium, the only source of non-dietary exposure is from golf course turf. For

that scenario, which is short-term in duration, we have included the turf exposure for populations

greater than 12 years of age only.

Drinking Water Levels of Comparison. The various single-pathway exposure estimates,

target MOEs and NOAELs were used to calculate risk quotients (Eqn. 1) which were then

combined to give aggregate risk quotients (Eqn. 2). The aggregate risk quotients, the oral

NOAELs, and target MOEs were then used to calculate the maximum allowable drinking water

exposures and the DWLOCs for each population subgroup (Equations 3 & 4). Based on

standard expressions of NOAELs in terms of mg/kg/day, body weight in kg, and water

consumption in L/day, the resulting DWLOCs are in terms of :g/L (ppb).

Aggregate Risk Quotient (ARQ) = RQDietary + RQNon-dietary Oral + RQDermal + RQInhalation (2)

5.1 Acute Risk

Acute aggregate risk estimates include only dietary pathways of exposure and drinking

water is addressed via DWLOCs. Non-dietary oral, dermal, and inhalation are not applicable

routes for assessing acute exposure and their contribution, as a risk quotient, is zero. The dietary

risk quotients are all well below the target risk quotient of one, indicating that there are not

pathway-specific risks of concern. As shown in Table 5.1.2, the acute DWLOCs are at least 4

orders of magnitude greater than the EECs for all of the population subgroups. Therefore, acute

aggregate risks are not likely to exceed HED’s level of concern.
24 of 32

Table 5.1.1. Acute Risk Quotients for Trifloxysulfuron-sodium.

Population Subgroup NOAEL (mg/kg) Exposure (mg/kg) Target MOE Risk Quotient

Dietary

General U.S. Population 600 0.00020 100 0.00003

All Infants < 1 year 600 0.00010 100 0.00002

Children 1-2 years 600 0.00074 100 0.00012

Females 13-49 years 50 0.00020 100 0.00040

Table 5.1.2. Acute Drinking Water Levels of Comparison for Trifloxysulfuron-sodium.

Pop.

Subgroup

Body

Weight,

kg

Water

Consump.,

L/Day

Risk Quotient Aggregate

Food NonDietary

Oral

Dermal Inhalation Aggregate MADWE,

mg/kg b 

DWLOC,

:g/L c

EEC,

:g/L d

General

U.S. Pop.

70 2 0.00003 0 0 0 0.00003 5.9998 210000 10.26

All Infants

< 1 year

10 1 0.00002 0 0 0 0.00002 5.9999 60000 10.26

Children

1-2 years

10 1 0.00012 0 0 0 0.00012 5.9993 60000 10.26

Females

13-49 years

60 2 0.00040 0 0 0 0.00040 0.4998 15000 10.26

a WC = Water Consumption

b MADWE = Max. Allowable Drinking Water Exposure = Dietary NOAEL ÷ Target MOE × {1-Aggregate Risk Quotient} c DWLOC = MADWE × 1000 :g/mg × Body Weight ÷ Water Consumption. Values are rounded to 2 significant figures. D Surface water estimated environmental concentration. The ground water EEC is 0.054 :g/L.

NA = Not Applicable

5.2 Short-Term Risk

Short-term aggregate risk includes the chronic estimated dietary exposure plus estimated

dermal exposure resulting from the proposed use of trifloxysulfuron-sodium on turf. Note that

exposure from this use is only applied to populations older than 12 years. In aggregating the

short-term risk HED has used the NOAEL of 79 m/kg/day from the 2-generation reporduction

study in rats (appropriate for short-term, incidental, oral exposure) to evaluate the dietary

pathway, and the NOAEL of 100 mg/kg/day from the 28-day dermal toxicity study in rats

(appropriate for short-term, dermal exposure) to evaluate the non-dietary pathway. For both

pathways, the target MOE is 100. The resulting risk quotients for the dietary and dermal

pathways are all well below the target risk quotient of one (Table 5.2.1), indicating that there are

not pathway-specific risks of concern. As shown in Table 5.2.2, the short-term DWLOCs are at

least 3 orders of magnitude greater than the EECs for all of the population subgroups. Therefore,

short-term aggregate risks are not likely to exceed HED’s level of concern.
25 of 32

Table 5.2.1. Short-term Risk Quotients for Trifloxysulfuron-sodium.

Population Subgroup NOAEL (mg/kg) Exposure (mg/kg) Target MOE Risk Quotient

Dietary

General U.S. Population 79 0.000057 100 0.00007

Youth 13-19 years 79 0.000058 100 0.00007

Females 13-49 years 79 0.000044 100 0.00006

Dermal

General U.S. Population 100 0.0005 100 0.00050

Youth 13-19 years 100 0.0005 100 0.00050

Females 13-49 years 100 0.0005 100 0.00050

Table 5.2.2. Short-term Drinking Water Levels of Comparison for Trifloxysulfuron-sodium.

Pop.

Subgroup

Body

Weight,

kg

Water

Consump.,

L/Day

Risk Quotient Aggregate

Food NonDietary

Oral

Dermal Inhalation Aggregate MADWE,

mg/kg b 

DWLOC,

:g/L c

EEC,

:g/L d

General

U.S. Pop.

70 2 0.00007 0 0.00050 0 0.00057 0.7895 28000 0.83

Youth 13-

19 years

60 2 0.00007 0 0.00050 0 0.00057 0.7895 24000 0.83

Females

13-49 years

60 2 0.00006 0 0.00050 0 0.00056 0.7896 24000 0.83

a WC = Water Consumption

b MADWE = Max. Allowable Drinking Water Exposure = Dietary NOAEL ÷ Target MOE × {1-Aggregate Risk Quotient} c DWLOC = MADWE × 1000 :g/mg × Body Weight ÷ Water Consumption. Values are rounded to 2 significant figures. D Surface water estimated environmental concentration. The ground water EEC is 0.054 :g/L.

NA = Not Applicable

5.3 Intermediate-Term Risk

There are no requested uses for trifloxysulfuron-sodium that require an assessment of

intermediate-term aggregate risk.

5.4 Chronic Risk

Based on the proposed uses of trifloxysulfuron-sodium, chronic aggregate risk estimates

need to include only dietary pathways of exposure with the drinking water component addressed

via DWLOCs. In the present situation non-dietary oral, dermal, and inhalation are not applicable

routes for assessing chronic exposure and their contribution, as a risk quotient, is zero. The

dietary risk quotients are all well below the target risk quotient of one, indicating that there are

not pathway-specific risks of concern. As shown in Table 5.4.2, the chronic DWLOCs are at

least 3 orders of magnitude greater than the EECs for all of the population subgroups. Therefore,

chronic aggregate risks are not likely to exceed HED’s level of concern.
26 of 32

Table 5.4.1. Chronic Risk Quotients for Trifloxysulfuron-sodium.

Population Subgroup NOAEL (mg/kg) Exposure (mg/kg) Target MOE Risk Quotient

Dietary

General U.S. Population 23.7 0.000057 100 0.00024

All Infants < 1 year 23.7 0.000028 100 0.00012

Children 1-2 years 23.7 0.000170 100 0.00072

Females 13-49 years 23.7 0.000044 100 0.00019

Table 5.4.2. Chronic Drinking Water Levels of Comparison for Trifloxysulfuron-sodium.

Pop.

Subgroup

Body

Weight,

kg

Water

Consump.,

L/Day

Risk Quotient Aggregate

Food NonDietary

Oral

Dermal Inhalation Aggregate MADWE,

mg/kg b 

DWLOC,

:g/L c

EEC,

:g/L d

General

U.S. Pop.

70 2 0.00007 0 0 0 0.00007 0.2370 8300 0.83

All Infants

< 1 year

10 1 0.00007 0 0 0 0.00007 0.2370 2400 0.83

Children 1-

2 years

10 1 0.00006 0 0 0 0.00006 0.2370 2400 0.83

Females

13-49 years

60 2 0.00000 0 0 0 0.00000 0.2370 7100 0.83

a WC = Water Consumption

b MADWE = Max. Allowable Drinking Water Exposure = Dietary NOAEL ÷ Target MOE × {1-Aggregate Risk Quotient} c DWLOC = MADWE × 1000 :g/mg × Body Weight ÷ Water Consumption. Values are rounded to 2 significant figures. D Surface water estimated environmental concentration. The ground water EEC is 0.054 :g/L.

NA = Not Applicable

5.5 Cancer Risk

Trifloxysulfuron-sodium has been classified as “Not likely to be carcinogenic to

humans.” Therefore, an assessment of aggregate cancer risk is not required.

6.0 CUMULATIVE RISK

The Food Quality Protection Act (1996) stipulates that when determining the safety of a

pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among

other things, available information concerning the cumulative effects to human health that may

result from dietary, residential, or other non-occupational exposure to other substances that have

a common mechanism of toxicity. The reason for consideration of other substances is due to the

possibility that low-level exposures to multiple chemical substances that cause a common toxic

effect by a common mechanism could lead to the same adverse health effect as would a higher

level of exposure to any of the other substances individually. A person exposed to a pesticide at

a level that is considered safe may in fact experience harm if that person is also exposed to other

substances that cause a common toxic effect by a mechanism common with that of the subject

pesticide, even if the individual exposure levels to the other substances are also considered safe.

HED did not perform a cumulative risk assessment as part of this risk assessment for
27 of 32

trifloxysulfuron-sodium because HED has not yet initiated a review to determine if there are any

other chemical substances that have a mechanism of toxicity in humans in common with it. For

purposes of this petition, EPA has assumed that trifloxysulfuron does not have a common

mechanism of toxicity with other substances. We note, however, that the metabolite CGA053052 which was identified as a residue of concern in water is a metabolite of other

sulfonylurea herbicides.

On this basis, the petitioner must submit, upon EPA's request and according to a schedule

determined by the Agency, such information as the Agency directs to be submitted in order to

evaluate issues related to whether trifloxysulfuron shares a common mechanism of toxicity with

any other substance and, if so, whether any tolerances for trifloxysulfuron need to be modified or

revoked. If HED identifies other substances that share a common mechanism of toxicity with

trifloxysulfuron, HED will perform aggregate exposure assessments on each chemical, and will

begin to conduct a cumulative risk assessment. 

HED has recently finalized its guidance for conducting cumulative risk assessments on

substances that have a common mechanism of toxicity. This guidance is available from the OPP

Website (http://www.epa.gov/pesticides). In the guidance, it is stated that a cumulative risk

assessment of substances that cause a common toxic effect by a common mechanism will not be

conducted until an aggregate exposure assessment of each substance has been completed.

Before undertaking a cumulative risk assessment, HED will follow procedures for

identifying chemicals that have a common mechanism of toxicity as set forth in the "Guidance

for Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of

Toxicity" (64 FR 5795-5796, February 5, 1999).

7.0 OCCUPATIONAL EXPOSURE

(S. Wang, D284482, 9/20/03)

HED has assessed occupational exposures for application as well as postapplication

activities on the following crops: cotton, sugarcane, citrus, almonds, tomatoes, and turfgrass. 

Based on the frequency of applications and application intervals provided in the proposed label,

EPA assumes that both on-farm application handlers and post-application workers would be

exposed for less than 30 days per year (short-term exposure) and that commercial pesticide

handlers could be exposed for more than 30 days but less than 6 months (intermediate-term

exposure). The NOAEL of 45 mg/kg/day assigned to be used in intermediate-term dermal

assessments is from an oral study. Due to the use of a 30% dermal absorption factor, the

“equivalent” dermal NOAEL is 150 mg/kg/day. Since this value is greater than the NOAEL of

100 mg/kg/day assigned for short-term dermal assessments, the short-term assessment is

protective of intermediate-term exposures; therefore, an intermediate term assessment has not

been conducted. Long-term exposure is not expected.

Margins of exposure for all of the application (Table 6.1) and postapplication (Table 6.2)

activities are much greater than the target MOE of 100. 
28 of 32

No chemical-specific data for assessing human exposures during pesticide handling

activities were submitted to the Agency in support of the registration of trifloxysulfuron-sodium. 

Therefore, HED used surrogate data from the Pesticide Handlers Exposure Database (PHED) 

Version 1.1. (8/98). Defaults established by the HED Science Advisory Council for Exposure

(Exposure SAC) were used for acres treated per day and body weight. MOEs for the handlers

performing agricultural crop uses ranged from 22,000 to 5,400,000 at the baseline level of

personal protective equipment (PPE). MOEs for the handlers performing turfgrass uses ranged

from 75,000 to 3,800,000 at the baseline level of PPE. The PPE on the proposed label specifies

that applicators and other handlers wear long-sleeved shirt, long pants, waterproof gloves, and

shoes plus socks. Based on the chemical properties of trifloxysulfuron-sodium (Table 2.2), there

is low probability for inhalation exposure to this chemical. Therefore, inhalation exposures were

not aggregated with dermal exposures for the occupational assessment.

The occupational post-application exposure/risk were calculated using activity specific

transfer coefficient (Tc) values from the HED Exposure SAC Policy Number 3.1. Postapplication MOEs from this screening-level assessment ranged from 2,000 to 290,000. The

assessment assumed exposure of 8 hours per day for 30 days per year. The default body weight

for female workers (60 kg) was used since the regulatory endpoint was noted in females and use

of this body weight produces an exposure estimate which is protective of both male and female

workers.

Table 6.1. Short-term Occupational Exposure and Risk Estimates for Trifloxysulfuron-sodium. All

estimates are at baseline mitigation (long-sleeve shirt, long pants, shoes, and socks and no respirator). The dermal

NOAEL is 100 mg/kg/day; the inhalation NOAEL is 50 mg/kg/day.

Exposure Scenario

(Scenario #)

Crop Daily

Dermal

Dose, mg/kg/day

Daily

Inhalation

Dose, mg/kg/day

Dermal

MOE

Inhalation

MOE

Mixer/Loader

Dry Flowables for Groundboom application (1)Cotton 0.00260 0.000030 38,000 1,700,000

Sugarcane 0.00248 0.000029 40,000 1,700,000

Tomato 0.00084 0.0000097 120,000 5,200,000

Turfgrass 0.00115 0.000013 87,000 3,800,000

Dry Flowables for Air Blast

application (2)

Citrus and

Almonds

0.00083 0.0000096 120,000 5,200,000

Applicator

Sprays with 

Ground-boom (3)

Cotton 0.00055 0.000029 180,000 1,700,000

Sugarcane 0.00053 0.000028 190,000 1,800,000

Tomato 0.00018 0.0000093 560,000 5,400,000

Turfgrass 0.00025 0.000013 400,000 3,800,000

Sprays with 

Air Blast (4)

Citrus and

Almonds

0.0045 0.000056 22,000 890,000
Table 6.1. Short-term Occupational Exposure and Risk Estimates for Trifloxysulfuron-sodium. All

estimates are at baseline mitigation (long-sleeve shirt, long pants, shoes, and socks and no respirator). The dermal

NOAEL is 100 mg/kg/day; the inhalation NOAEL is 50 mg/kg/day.

Exposure Scenario

(Scenario #)

Crop Daily

Dermal

Dose, mg/kg/day

Daily

Inhalation

Dose, mg/kg/day

Dermal

MOE

Inhalation

MOE

29 of 32

Mixer/Loader/Applicator

Sprays with Back Pack

Sprayer (5)

Turfgrass 0.00133 0.000016 75,000 3,100,000

Table 6.2. Post-application Occupational Exposure and Risk Estimates for Trifloxysulfuron-sodium. All

estimates are for zero days after the final application.

Crop Work Activity Daily Dose

(mg/kg/day) MOE

Cotton

Irrigation, scouting, thinning, weeding immature/low foliage plants 0.00035 290,000

Irrigation, scouting, weeding mature/high foliage plants 0.0053 19,000

Hand harvesting 0.0088 11,000

Sugarcane

Scouting immature plants 0.0084 12,000

Scouting mature plants 0.0169 6,000

Citrus

Propping 0.0006 180,000

Irrigation, scouting, hand weeding 0.0060 18,000

Harvesting, pruning, training, tying, thinning 0.017 6,000

Harvesting, thinning, pollination, bagging, tying, misc. hand labor,

staking topping, training 0.045 2,000

Almonds

Irrigation, scouting, thinning, weeding 0.0030 36,000

Harvesting/poling, pruning, thinning 0.014 7,000

Tomatoes

Irrigation, scouting, thinning, weeding immature plants 0.0014 70,000

Irrigation/scouting mature plants 0.0020 50,000

Hand harvesting, pruning, staking, tying 0.0028 35,000

Turfgrass

Mowing 0.0010 100,000

 Transplanting, hand weeding 0.032 3,100
30 of 32

8.0 DATA NEEDS AND LABEL REQUIREMENTS

8.1 Toxicology

No data gaps. Although HIARC recommended that a 90-day inhalation toxicity study in

rats be required to be submitted to the Agency within a reasonable period of time (7/22/03, TXR

No. 0052043), this requirement is waived for the registrations and tolerances addressed in this

document. This waiver is in accordance with Criteria 4 in SOP 2002.01 - “HED Standard

Operating Procedure: Guidance: Waiver Criteria for Multiple-Exposure Inhalation Toxicity

Studies” (8/15/02), which states that “a waiver may be granted for an active ingredient that is

Toxicity Category IV for inhalation provided an extrapolated inhalation MOE (based on an oral

NOAEL) exceeds a target MOE of 1000 or greater”. Trifloxysulfuron-sodium is Toxicity

Category IV for inhalation (Table 3.1) and the extrapolated inhalation MOEs for short-term

occupational exposures range from 890,000 to 5,400,000 (Table 6.1). Inhalation exposures and

risk assessments were not conducted for any of the other exposure scenarios described in this

document because inhalation exposure is not expected to be significant based on low vapor

pressure (<1 x 10-7 Pa, Table 2.2) and dilution by outdoor air.

8.2 Residue Chemistry

860.1200 Directions for Use. The use directions for cotton should be modified to clarify

the use patterns/situations when tank mixing with other herbicides is allowable.

860.1340 Residue Analytical Methods. The HPLC/UV method will be submitted to the

ACL for Agency tolerance method validation (TMV). We note that the laboratory that

conducted the ILV for the method recommended some changes/clarifications to the method

procedures, including correction of a typographical error. Unless ACL concludes differently, the

modifications recommended by the ILV laboratory will have to be made to the method prior to

its acceptance as a tolerance enforcement method; any additional changes recommended by ACL

will also have to be incorporated.

860.1500 Crop Field Trials. The submitted cotton field trial data cannot be used to

support the proposed use on cotton because the field trial studies were conducted at application

rates that were -3x the proposed maximum seasonal rate. The petitioner should submit field trial

data for cotton seed and gin byproducts reflecting application of trifloxysulfuron-sodium at 1x

the maximum proposed application rate (0.019 lb ai/A) or submit a revised label reflecting the

use pattern used to conduct the cotton field trials. Also, HED is requesting clarification that the

cotton field trial samples were harvested by picker equipment since the requested use is for

picker varieties of cotton only. The currently available data are sufficient for a conditional

registration.

860.1550 Proposed Tolerances. The petitioner must revise the tolerance definition to

remove the phrase “and metabolites converted to parent equivalents” and the reference to the

sodium salt (i.e., the tolerance expression should be for trifloxysulfuron). Due to the level of

apparent residues of trifloxysulfuron in control samples of almond nutmeat, and citrus
31 of 32

commodities, HED recommends that the proposed tolerances be increased in those commodities

to ensure that tolerances are greater than 5 times the apparent residues. The recommended

tolerance levels, as well as corrections to the commodity definitions, are presented in Table 8.1. 

A revised Section F is requested.

8.3 Occupational and Residential Exposure

According to the information provided by the registrant, there are no requested

residential uses for trifloxysulfuron at this time. HED recommends that “for use on golf courses

only” be explicitly included on the turf label.

Table 8.1. Tolerance Summary for Trifloxysulfuron-sodium

Commodity Proposed

Tolerance

(ppm)

Recommended

Tolerance

(ppm)

Comments (correct commodity definition)

Almond Nutmeat 0.01 0.02* Almond

Almond Hulls 0.01 0.01 — 

Citrus 0.01 0.03* Fruit, citrus, group 10

Cottonseed 0.05 0.05 Cotton trials conducted at 3X max. rate. As a condition

of registration, the petitioner should submit data from

trials conducted at the maximum recommended rate or

revise the label to reflect the rate used in the field trials. 

Commodity Definition: cotton, undelinted seed

Cotton By-products 1.0 1.0 Cotton trials conducted at 3X max. rate. As a condition

of registration, the petitioner should submit data from

trials conducted at the maximum recommended rate or

revise the label to reflect the rate used in the field trials. 

Commodity Definition: cotton, gin by-products

Sugarcane 0.01 0.01 — 

Tomatoes 0.01 0.01 Tomato

* A higher tolerance is recommended due to apparent residues in control samples in excess of 20% of the

proposed tolerance

References:

1. Trifloxysulfuron-sodium - Report of the Hazard Identification Assessment Review

Committee. E. R. Budd and A. C. Levy. 7/22/03. TXR No. 0052043.

2. Toxicology Disciplinary Chapter for the Registration Support Document. E. R. Budd and

A. C. Levy. 8/21/03. TXR No. 0050906.

3. Trifloxysulfuron-sodium: Metabolism Assessment Review Committee Report. M. A.

Doherty, E. R. Budd, A. C. Levy, S. C. Termes. 8/25/03. DP Barcode D293085. TXR

No. 0052100.
32 of 32

4. Trifloxysulfuron-sodium. Section 3 Registration Request for Food Uses on Almond,

Citrus (Group 10), Cotton, Sugarcane, and Tomato. Summary of Analytical Chemistry

and Residue Data. Petition Number 1F06280. M. A. Doherty. 8/25/03. DP Barcode

D284480.

5. Trifloxysulfuron-sodium: Acute and Chronic Dietary Exposure Assessments for the

Section 3 Registration on Almonds, Citrus, Cotton, Sugarcane, and Tomato (PP#

1F06280). M. A. Doherty. 8/25/03. DP Barcode D293086.

6. Drinking water assessment for Trifloxysulfuron Sodium (“Trifloxysulfuron”) for use on

cotton, sugarcane, almonds, citrus, tomatoes, and turf. J. K. Wolf and S. C. Termes. 

8/20/03. DP Barcode D276988, D280727, D284104, D284108, D284113, D284117,

D284478, D284116.

7. Occupational and Residential Exposure/Risk Assessment for a New Active Ingredient,

Trifloxysulfuron, on Cotton, Sugarcane, Citrus, Almonds, Tomatoes, and Turfgrass. S.

Wang. 9/20/03. DP Barcode D284482.

cc (without attachments): M. Doherty, E. Budd, A. Levy, S. Wang, RAB 2 Reading File