UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: May 8, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: TriOoxysulfuron-sodium. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Codes: 119009 

Decision No.: 474095 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: D408404 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 7028 

CAS No.: 145099-21-4 (free sulfonylurea), 

199119-58-9 (sodium salt), 

290332-10-4 (sodium salt monohydrate) 

40 CFR: 180.591 

FROM: Elizabeth 

Linne a Hansen

Holman

, Ph.D

, Ph

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Risk Assessment Branch II 

Matth

Risk Assessment 

ew Lloyd, C

Branch 

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~ ~ Health Effects Division (7509P) 

Office of Pesticide Programs 

THROUGH: Christina Swartz, Branch Chief 

Risk Assessment Branch II 

Jess Rowland, Acting Associate Director ka.C2o~ Dana Vogel, Associate Director "'/'if"\· .. _s:::z.____.--

Health Effects Division (7 509P) \ '\ \ ~ 

Office of Pesticide Programs 

TO: Kelly Ballard, Chemical Review Manager 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs 

Page 1 of23 
Attached is the Health Effects Division's (HED) human health risk assessment seeping document for 

trifloxysulfuron-sodium to support registration review. 

Executive Summary 

The Health Effects Division trifloxysulfuron-sodiurn Risk Assessment Team has evaluated the 

database and the most recent human health risk assessments for the sulfonylurea herbicide 

trifloxysulfuron-sodiurn. HED performed this evaluation in order to determine the scope of work 

necessary to support the established tolerances and existing registrations. The primary sources of 

information for this evaluation were recent human health risk assessments written for this 

chemical. 

Trifloxysulfuron-sodium, a broad-spectrum, low-application rate sulfonylurea herbicide, is 

currently registered for use on numerous agricultural food/feed crops, including almonds, citrus, 

cotton (picker variety only), sugarcane and tomatoes. Non-agricultural uses include sports fields 

and residential turf grass. Like other herbicides in this class, trifloxysulfuron-sodium acts by 

inhibiting the plant enzyme acetolactate synthase, resulting in reduced production of branchedchain amino acids. The primary registered end-use product (EP) is a 75% wettable granule 

(WG) formulation. Application is via ground and handheld application equipment only (groundboom, back pack sprayer and airblast); aerial applications are prohibited. There are no 

international registrations of trifloxysulfuron-sodium under Codex, or in Canada and Mexico. 

The toxicological database for trifloxysulfuron-sodium is complete for the purpose of 

registration review. Although the subchronic inhalation study is listed as being required per the 

pesticide registration data requirements published in Title 40 Part 158 of the Code of Federal 

Regulations (CFR), the Hazard and Science Policy Council (HASPOC) has determined, based on 

the available data and the weight of the evidence, that the subchronic inhalation study is not 

required (TXR# 0056564). HED previously determined that a dermal penetration study is not 

required (Memo, D352260, M. Doherty eta!., 11/12/2008). HED continues to support this 

conclusion, and will not require submission of the· study during registration review. 

As a class, suflonylureas exhibit relatively low toxicity, and the database for trifloxysulfuronsodium is typical of the toxicity seen with the class overall. Primarily, effects were seen in the 

kidneys, the urinary bladder, the liver, heart development, body weight gain, motor activity, 

and lung tissue at relatively high dose levels. Trifloxysulfuron-sodium is classified as "not 

likely to be carcinogenic to humans" and there is no evidence of mutagenicity in genotoxicity 

studies. The required 1 OX Food Quality Protection Act (FQP A) safety factor was reduced to 

IX in the most current risk assessment based on hazard and exposure considerations. During 

registration review, it is unlikely that the endpoints, doses, and safety factors used in the most 

recent human health risk assessments would be reconsidered, unless new data are received. 

The most recent risk assessment (2008; D352260) for trifloxysulfuron-sodium addresses 

potential risks associated with dietary, residential post-application (dermal and oral) and 

occupational (dermal and inhalation) exposures. In the absence of a route-specific inhalation 

Page 2 of23 
Page 3 of 23

toxicity study, the inhalation risk assessment was based on the point of departure (POD) and the 

endpoint from an oral toxicity study. 

Acute and chronic dietary exposure was assessed for all populations. The acute dietary 

endpoints selected were decreased motor activity in the rat acute neurotoxicity study for the 

general population, and heart malformations in the rabbit developmental study for females age 

13-49. The chronic dietary endpoint selected was kidney pathology in the rat two-year chronic 

toxicity/carcinogenicity study, considered relevant for all populations. Incidental oral exposure 

was assessed using the rat two-generation reproductive toxicity study, based on decreased pup 

weights. 

The dietary exposure database is adequate to support the registration review of trifloxysulfuronsodium. However, if the dietary endpoints change or new drinking water estimates become 

available, an updated dietary risk assessment could be needed. Currently, there are no dietary 

risk estimates of concern for the existing uses of trifloxysulfuron-sodium. 

Current uses of trifloxysulfuron-sodium on turf are likely limited to commercial or professional 

applicators only, although trifloxysulfuron-sodium is not a restricted use product. Nonoccupational or residential handlers’ exposure has not been assessed in the past, but will be 

evaluated during registration review since “commercial applicators only” language is not 

enforceable. Post-application residential and occupational inhalation exposure was not 

previously assessed due to the low volatility of trifloxysulfuron-sodium. All exposures are

expected to be of short- or intermediate-term duration. 

The residential exposure database is adequate to support registration review for trifloxysulfuronsodium. Although a turf transferable residue study is required under the updated Part 158 data 

requirements (2007) for all occupational (e.g., sod farms, golf courses, parks, and recreational 

areas) or residential turf uses, HED has determined that this study is not needed for 

trifloxysulfuron-sodium. This decision is consistent with current HED policy, given that the risk 

estimates calculated for the residential post-application scenarios are well above the level of 

concern. An updated residential exposure assessment may be needed during registration review 

as a result of the revisions to HED’s Residential Exposure Standard Operating Procedures 

(SOPs). Furthermore, because of the potential for residential bystander exposure to

trifloxysulfuron-sodium from airblast applications, volatilization, and/or transport from treated 

areas (drift), HED will evaluate the need for a bystander assessment during registration review. 

For trifloxysulfuron-sodium, residential exposures are aggregated with dietary exposures. In the 

most recent human health risk assessment, there were no aggregate risk estimates of concern 

(Memo, D352260, M. Doherty et al., 11/12/2008). During registration review, an updated 

aggregate risk assessment may be needed to incorporate residential handler exposure estimates or 

any potential changes in exposure from drinking water. 

The occupational exposure database is adequate to support registration review for 

trifloxysulfuron-sodium. There are no occupational handler and post-application risk estimates 

of concern. Although no chemical-specific dislodgeable foliar residue (DFR) data are available, 

these data are not required for the current uses based on weight of evidence considerations. This 
Page 4 of 23

conclusion may change if new uses and/or higher application rates are proposed. HED will 

consider the need for an updated occupational exposure assessment during registration review, 

but at this time it is not considered likely.

Introduction

HED evaluated the most recent human health risk assessments for trifloxysulfuron-sodium in 

association with the updates to their toxicity, exposure, and usage databases to determine if 

sufficient data are available and if further updates are needed to support registration review. 

Recent human health risk assessments include the 2008 assessment for the use of 

trifloxysulfuron-sodium on sports fields and residential turfgrass (Memo, D352260, M. Doherty

et al., 11/12/2008). In addition, HED considered the latest Agency science policies and risk 

assessment methodologies. The structure of trifloxysulfuron-sodium, as well as its chemical 

name and other identifiers can be found in the chemical identity table attached to this document

(Attachment 1).

Trifloxysulfuron-sodium is registered for use on sugarcane, tomato, almonds, citrus, and cotton. 

The associated tolerances for residues of trifloxysulfuron in the corresponding raw agricultural 

commodities are listed in 40 CFR 180.591, with values ranging from 0.01 to 1.0 ppm (see 

Attachment 2). Non-agricultural uses include sports fields and residential turf grass. Current

labels for trifloxysulfuron-sodium use on turf contain language stating that the products are to be 

used by commercial or professional applicators only, although trifloxysulfuron-sodium is not a 

restricted use product. HED notes that this label language is not considered enforceable, and 

therefore assumes a residential homeowner could purchase and use the product. The end use 

products and sites are summarized in Attachment 3. 

Hazard Identification/Toxicology

The toxicological database for trifloxysulfuron-sodium is largely complete, missing only a 

subchronic inhalation study and a dermal penetration study. Although the subchronic inhalation 

study is listed as being required per the pesticide registration data requirements published in Title 

40 Part 158 of the Code of Federal Regulations (CFR), the Hazard and Science Policy Council 

(HASPOC) has determined, based on the available data and the weight of the evidence, that the 

subchronic inhalation study is not required (TXR# 0056564). The HASPOC conclusion was 

based on considerations such as the low acute inhalation toxicity; the low vapor pressure of 

trifloxysulfuron-sodium; the low risks estimated for occupational workers exposed via the 

inhalation route with the use of an oral point of departure (POD); and the overall conclusion that 

any potential endpoint such as portal of entry effects from a subchronic inhalation toxicity study 

would not be more protective than the available POD from an oral study.

A developmental neurotoxicity study (DNT) is listed as being conditionally required under Title 

40 Part 158 of the CFR. However, HED previously determined that a DNT study is not required 

based on the overall toxicity database and weight of evidence, including the lack of neurotoxicity 

observed in the subchronic neurotoxicity study in rats, as well as subchronic or chronic studies in 

rats, mice, and dogs (Memo, D352260, M. Doherty et al., 11/12/2008). HED continues to 

support this conclusion, and will not require submission of the study during registration review.
Page 5 of 23

A dermal penetration study is also listed as being conditionally required under Title 40 Part 158 

of the CFR. In the submitted 21/28-day dermal toxicity study, 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 the most recent 

risk assessment (Memo, D352260, M. Doherty et al., 11/12/2008), endpoints and doses for 

dermal risk assessment were chosen from oral studies. In the case of the short-term endpoint, 

developmental effects in the rabbit were selected (fetal heart abnormalities) and in the case of the 

intermediate-term endpoint, lung effects, decreased body weight gains and urinary bladder 

inflammation were selected from a chronic dog study. In both cases, the doses (no observed 

adverse effects levels, or NOAELs), selected were lower than the dose observed in the dermal 

study; the dermal study did not evaluate developmental effects and would not have been 

considered protective of potentially pregnant females. In the case of the intermediate-term 

assessment, the use of the oral POD was considered to be protective.

Since oral doses and endpoints were selected for both short and intermediate-term dermal risk 

assessment, a dermal absorption factor of 30% was applied in this most recent risk assessment. 

This dermal absorption factor was derived from dermal absorption data available from other 

sulfonylurea herbicides. During registration review, HED may assess whether this dermal 

absorption factor needs to be updated based on currently available information on sulfonylureas. 

Regardless, even if the estimated dermal absorption factor were to change, the dermal 

penetration study is not required at this time and HED does not anticipate risks of concern 

associated with dermal exposure. 

An immunotoxicity study was recently submitted and has been reviewed by HED (MRID 

48857701). This review indicates that the study is acceptable and that the results show no 

evidence of immunotoxicity for trifloxysulfuron-sodium. These results are consistent with the 

existing toxicological database for trifloxysulfuron-sodium which does not indicate that the 

chemical targets the immune system. Given the above information, HED concludes that this new 

immunotoxicity study has no impact on the overall assessment and revisions to the toxicological 

endpoints will not be required during registration review. The doses and endpoints selected 

(along with traditional uncertainty factors) are considered protective of potential 

immunotoxicity. 

As a class, suflonylureas exhibit relatively low toxicity, and the database for trifloxysulfuronsodium is typical of the toxicity seen with the class overall. Primarily, effects were seen in the 

kidneys, the urinary bladder, the liver, heart development, body weight gain, motor activity, and 

lung tissue at relatively high dose levels. Other effects observed in the toxicological database 

included testicular atrophy and organ weight changes (e.g. thymus, spleen); however, these 

changes were observed at doses higher than those used as endpoints for risk assessment. 

There was no evidence of carcinogenicity seen in mice and rats. Mutagenicity studies were also 

all negative. An acceptable rat metabolism study is also available. 

The LD50 acute (lethality) studies generally reflected a low level of toxicity: The acute oral study 

in rats, the acute inhalation in rats, and the primary skin irritation in rabbits were category IV; the 
Page 6 of 23

acute dermal in rats and the primary eye irritation in rabbits were category III. Trifloxysulfuronsodium is not a dermal sensitizer in the dermal sensitization study with guinea pigs.

There was no evidence of increased pre- and/or postnatal quantitative and qualitative 

susceptibility in the rat. Developmental effects observed in the prenatal developmental rat study

(decreased weight gain and increased skeletal variations) and offspring effects observed in the rat 

reproduction study (decreased pup weight/weight gain, decreased spleen and thymus weight and 

increased vaginal patency) were observed at the same doses that caused maternal effects. There 

was evidence of increased quantitative susceptibility in the prenatal developmental study in 

rabbits. The maternal NOAEL was 100 mg/kg/day based on mortality and vaginal/anal bleeding 

observed at the lowest observed adverse effects level (LOAEL) of 250 mg/kg/day, but at 100 

mg/kg/day, fetal heart abnormalities were observed. However, concern for this effect is low 

because there was a clear NOAEL (50 mg/kg/day) and only a single fetus was affected at the 

LOAEL. In addition, the endpoint and dose from the study were selected for relevant exposed 

populations, and therefore the risk assessment is protective of the observed susceptibility.

In the most recent risk assessment, the required 10X FQPA safety factor was reduced to 1X 

based on: 1) the completeness of the toxicology database; 2) the lack of increased pre- and 

postnatal susceptibility of rats to in utero and/or postnatal exposure in the developmental and 

reproductive toxicity studies; and 3) the conservative nature of the dietary, occupational, and 

residential exposure assessments. Although there was evidence of increase quantitative 

susceptibility in the developmental toxicity study in rabbits, the degree of concern is low because 

there was a clear NOAEL for the effect; only one fetus had the effect at the LOAEL; the effect 

was characterized as an abnormality (rather than a malformation); and the effect is being used as 

a toxicological endpoint in appropriate risk assessments. 

These conclusions are not expected to change during registration review. The toxicological 

endpoints and doses used in the most recent human health risk assessment are summarized in 

Attachment 4. The toxicity profile of trifloxysulfuron-sodium is summarized in Attachment 5. 

Conclusions for Hazard Identification/Toxicology

The toxicity database is considered complete for the purpose of registration review, allowing for 

assessment of potential carcinogenic, mutagenic, developmental, and reproductive effects. In the 

most recent risk assessment, the FQPA safety factor was reduced to 1X based on a number of 

factors including the completeness of the database, the lack of susceptibility in developmental 

and reproduction studies in rats, the low level of concern for the quantitative susceptibility 

observed in the developmental study in rabbits, and the conservative assumptions used in the 

exposure assessments. During registration review, HED will consider the appropriateness of the 

existing endpoints based on current policies and risk assessment methodologies. However, no 

significant rework is anticipated to the endpoints, doses, and safety factors used for risk 

assessment. . 

Dietary Exposure
Page 7 of 23

Tolerances for trifloxysulfuron-sodium are listed in 40 CFR 180.591 and range from 0.01 to 1.0 

ppm. The residue chemistry database for trifloxysulfuron-sodium is complete for the purpose of 

supporting the currently registered uses. HED has previously determined that the residue of 

concern in plants and livestock commodities for both tolerance enforcement and risk assessment 

purposes is parent trifloxysulfuron. In drinking water, the residues of concern for risk 

assessment purposes are parent trifloxysulfuron, as well as metabolites CGA-053052, CGA382997, and CGA-368732.

Dietary exposure estimates in the previous risk assessment assume 100% percent crop treated 

and directly incorporated estimated residues in drinking water. Residue estimates for drinking 

water are from models designed to produce high-end results. All dietary risk estimates were less 

than 1% of the acute and chronic population-adjusted dose and were, therefore, well below 

HED’s level of concern. 

Since the last dietary assessment, HED updated its dietary model to incorporate more recent 

consumption data from the National Health and Nutrition Examination Survey (NHANES). 

EFED recommended that modeled estimates of residues in drinking water be used in the most

recent dietary risk assessment. During registration review, HED will evaluate whether updated 

drinking water estimates are available and whether these revised estimates make it necessary to 

complete a new dietary assessment. Depending on the magnitude of any updates, a new dietary 

assessment may be required to appropriately estimate risks associated with drinking water 

exposure. 

Conclusions for Dietary Exposure

The dietary exposure database is adequate to support the existing registrations and tolerances. 

No new residue chemistry data are required. A new dietary assessment may be needed if one or 

more of the following occur: new data are identified which impact dietary exposure estimates, 

including those from drinking water; new toxicological points of departure are identified, 

including revisions to the FQPA SF; OPP dietary exposure policies and procedures are revised. 

HED recently updated its dietary model to incorporate more recent consumption data from the 

National Health and Nutrition Examination Survey (NHANES). This new version of the model 

will be used during registration review if a new dietary assessment is needed. 

Residential Exposure and Risk

Residential Handlers

Based on the current use pattern, there is potential for residential handler exposure. While 

trifloxysulfuron-sodium is likely mainly applied to turf and industrial turf (e.g., golf courses and 

other non-residential turf areas such as industrial parks, sod farms, seed farms, and professionally 

managed sports fields), it is not restricted from purchase or use by residential handlers. 

Therefore, during registration review HED will conduct a residential handler assessment using 

the most recent exposure methodology and toxicological endpoints.

Residential Post-Application 
Page 8 of 23

Based on the current use pattern, there is only potential for post-application dermal exposure for 

recreational golfers and individuals contacting treated turf in commercially treated areas. 

Trifloxysulfuron-sodium is restricted from use on residential turf/lawns.

In accordance with the updated Part 158 data requirements (2007), a turf-transferrable residue 

(TTR) study is required for all occupational (e.g., sod farms) or residential turf uses; TTR data 

are not available for trifloxysulfuron-sodium. As part of the recent revision to the Health Effects 

Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment, 

HED analyzed all of the available TTR data and selected new liquid and granular default values 

for the fraction of the application rate available for transfer after a turf application (FAR). This 

default is 0.2% for granular formulations. Of the available TTR studies submitted to the Agency, 

the maximum FAR value seen using a granular product was 0.69% or 3.5 times higher than the 

default residue transfer value. Therefore, HED has decided that a calculated MOE of 

approximately 10 times higher than the LOC (e.g., an MOE >1,000 if the LOC = 100) using the 

default residue transfer values would provide an adequate margin of safety for any potentially 

higher residues seen in a chemical-specific TTR study (HED Memo, 12/12/12, “Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

Studies”). For the current uses of trifloxysulfuron-sodium, a TTR study will not be required for 

Registration Review since estimated dermal MOEs for all residential post-application scenarios

are greater than 1000. If the use pattern and/or toxicological points of departure change in the 

future, this requirement may be revisited.

Spray Drift

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) might 

occur as a result of applications of trifloxysulfuron-sodium. The Agency is in the process of 

evaluating these types of exposures and might, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate these post-application exposures 

into the Agency’s risk assessments. The need for spray drift and volatilization risk assessment 

for trifloxysulfuron-sodium will be examined during registration review

Conclusions for Residential Exposure: 

A new risk assessment may be needed to address the short-term handler and post-application 

dermal exposure potential for recreational golfers and individuals (adults and children) 

contacting commercially treated turf. TTR data are not required for trifloxysulfuron based on a 

screen of 2012 Residential SOP revisions and the estimated risks from contacting treated turf.

Aggregate Risk Assessment

Aggregate assessments consider exposures from food, drinking water, and non-occupational 

sources. In the 2008 human health risk assessment (Memo, D352260, M. Doherty et al., 

11/12/2008), aggregate risks were estimated for the acute (food and drinking water), short-term 

(non-occupational, food and drinking water), and chronic (food and drinking water) exposure 

durations. The aggregate risks for each of the exposure durations were below HED’s level of 
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concern. However, the 2008 assessment did not account for recent policy and scientific changes 

in the disciplinary assessments. 

Conclusions for Aggregate Risk Assessment: 

For trifloxysulfuron-sodium, residential exposures are aggregated with dietary exposures. The 

2008 aggregate risk assessment did not identify risks of concern. However, during registration 

review HED may need to revisit the aggregate risks to include the latest policies for dietary 

assessment and methodological changes for calculating non-occupational exposure potential. 

During registration review, an updated aggregate risk assessment may be needed to incorporate 

residential handler exposure estimates or any potential changes in exposure from drinking water. 

Even if new assessments are needed, risks of concern are not anticipated.

Occupational Exposure

Trifloxysulfuron-sodium is currently registered for use on several agricultural crops as well as on 

golf course and other professionally managed turf areas. There is potential for short- and 

intermediate-term occupational exposure to trifloxysulfuron-sodium during handling (mixing, 

loading, and applying) and post-application activities.

Occupational Handlers

A revised occupational handler risk assessment may be needed for trifloxysulfuron-sodium.

Updated occupational handler exposure assessment may be required under registration review 

based upon revisions to the Agency’s scenario-specific surrogate handler exposure data. 

HED assessed occupational handler exposure in a 2003 risk assessment for the following 

agricultural crops: cotton, citrus, almonds, and transplanted tomatoes (D284104, M. Doherty, 

09/24/03). Additionally, in 2008 HED conducted an occupational assessment for commercial 

handlers of trifloxysulfuron for application to turf. 

Based on the 2003 risk assessment, the resulting risk estimates for occupational handlers treating 

agricultural crops were not of concern (margins of exposure, or MOEs, ranged from 22,000 to 

540,000, whereas MOEs >100 are not of concern). Occupational exposure and risk assessments 

for uses on golf course, sod farms athletic fields, industrial and commercial lawns and similar 

nonresidential areas resulted in risk estimates that were not of concern (MOEs ranged from 

75,000 to 3,800,000 assuming the baseline level of personal protective equipment, or PPE). 

Occupational Post-Application

A revised occupational post-application risk assessment may be needed for trifloxysulfuronsodium. There is a possibility for agricultural workers to have post-application dermal exposure 

to trifloxysulfuron-sodium following its uses. In the absence of chemical-specific data, the 2003 

and 2008 assessments were based on the registered use pattern for agricultural crops (cotton, 

sugarcane, citrus, almonds, and tomatoes) and commercial turf and on the use of default DFR 

and TTR assumptions.
Page 10 of 23

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are 

required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. There are currently no site- or chemical-specific DFR data for 

trifloxysulfuron-sodium. HED analyzed a number of DFR studies and selected a new default 

value for the fraction of the application rate available to be dislodged after a foliar application 

(FAR). This default value is 25%. Of the analyzed DFR studies, the maximum FAR value seen 

was 89% or 3.6 times higher than the default residue transfer value. Therefore, a calculated 

MOE of approximately 4 times higher than the LOC (i.e., an MOE >400 if the LOC = 100) using 

the default dislodged residue value would provide an adequate margin of safety for any 

potentially higher residues seen in a chemical-specific DFR study (HED Memo, 12/12/12, 

“Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar 

Residue (DFR) Studies”). A DFR study (875.2100) for trifloxysulfuron-sodium will not be 

required for Registration Review, since estimated post-application MOEs for occupational 

workers exposed to treated foliage from registered crops are all greater than 400 (MOEs range 

from 2,000 to 290,000). The requirement for a DFR study may need to be reconsidered if 

application rates, use patterns, or points of departure change. 

MOEs for the post-application agricultural scenarios included in the 2003 assessment ranged 

from 2,000 [harvesting/thinning citrus] to 290,000 [irrigating cotton]. The 2008 assessment 

evaluated occupational post-application exposure for turf maintenance; MOEs for those 

scenarios ranged from 5,400 to 180,000.

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment has not been performed for trifloxysulfuron-sodium. However, there are 

multiple potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for trifloxysulfuron-sodium.

Conclusions for Occupational Exposure:

There is sufficient information available to assess occupational handler and post-application 

exposures, and the relevant exposure scenarios have been assessed in the 2003 and 2008 

exposure assessments. However, not all of the occupational exposure scenarios were assessed 

based on current ORE policies. During registration review HED will consider the need for an 

up-to-date handler and post-application occupational assessment to account for these policy
Page 11 of 23

changes; if a new assessment is needed, potential changes to the endpoints and safety factors will 

be included. 

Public Health and Pesticide Epidemiology Data 

D408657, S. Recore, February 5, 2013

For this evaluation, both OPP Incident Data System (IDS) and the Centers for Disease Control 

and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel 

Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the active ingredient trifloxysulfuron-sodium (PC Code:

119009). Main IDS incidents involving only one pesticide are considered to provide more 

certain information about the potential effects of exposure from the pesticide. When an incident 

involves more than one pesticide, it is difficult to determine which effects are attributed to the 

pesticide being considered. The less severe human incidents (minor, unknown, or no effects 

outcomes) are reported by registrants as counts called aggregate summaries and are recorded in a 

separate module called Aggregate IDS. 

For the Main IDS, from January 1, 2007 to December 11, 2012, there were no incidents reported 

in the database involving trifloxysulfuron-sodium. 

In Aggregate IDS, from January 1, 2007 to December 11, 2012, there were 3 reported incidents 

involving trifloxysulfuron-sodium. These incidents were classified as minor severity. 

The NIOSH SENSOR database covers 11 states from 1998-2009, although reporting varies from 

state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. A query of SENSORPesticides 1998-2009 found no reported cases for trifloxysulfuron-sodium.

Trifloxysulfuron-sodium is not included in the Agricultural Health Survey (AHS), and therefore 

does not provide information for this report.

Based on the low frequency and low severity of incident cases reported for trifloxysulfuronsodium, there does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the registration review risk assessment.

Tolerance Assessment and International Harmonization

The qualitative nature of the residue for the existing uses has been adequately delineated based 

upon adequate metabolism studies in lemon, sugarcane, cotton, goats, and hens (memo, M. 

Doherty, 08/25/03, D284480). The residue definition for risk assessment and tolerance 

enforcement is the parent compound for both plant and livestock commodities. 
Page 12 of 23

Livestock feeding studies have not been submitted to date. Based on the feeding rate and 

resulting residues in the livestock metabolism studies, quantifiable residues of trifloxysulfuron 

are not expected to occur in meat, milk, poultry, and egg matrices. Due to this 40 CFR 

180.6(a)(3) situation, HED previously concluded that livestock feeding studies are not required 

and no livestock commodity tolerances have been established. Such studies may be required if 

new uses of trifloxysulfuron-sodium are sought for crops that are significant livestock feedstuffs. 

Such revisions would occur during new use risk assessments and would likely not need to be 

considered during registration review. 

During registration review, the tolerance expression should be revised to address both coverage 

and measurement:

The tolerance expression for trifloxysulfuron-sodium should be revised as follows:

“Tolerances are established for residues of trifloxysulfuron-sodium, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only 

trifloxysulfuron-sodium.” 

Currently, there are no established maximum residue limits (MRLs) for trifloxysulfuron-sodium 

in Canada, Mexico, or Codex. Therefore, international harmonization of regulatory levels will 

not be an issue for registration review.

The international residue limit status sheet can be found in Attachment 2. 

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures and risks based on home use of pesticide products for adult applicators and

postapplication activities for toddlers, youths, and adults entering or playing on treated areas are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.
Page 13 of 23

Endocrine Disruptor Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of trifloxysulfuron-sodium’s most recent registration decision, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

trifloxysulfuron-sodium is subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

Trifloxysulfuron-sodium is not among the group of 58 pesticide active ingredients on the initial 

list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue 

future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for 

trifloxysulfuron-sodium. For further information on the status of the EDSP, the policies and

procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening 

battery, please visit our website: http://www.epa.gov/endo/.

Cumulative Risk Assessments 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to trifloxysulfuron-sodium and any other substances, and trifloxysulfuron-sodium does not 

appear to produce a toxic metabolite produced by other substances. For the purposes of this 

action, therefore, EPA has not assumed that trifloxysulfuron-sodium has a common mechanism 

of toxicity with other substances. For information regarding EPA’s efforts to determine which 
Page 14 of 23

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning 

common mechanism determinations and procedures for cumulating effects from substances 

found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

Human Studies

The previous risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemical. These studies, which comprise the 

PHED, the Outdoor Residential Exposure Task Force (ORETF), and the Agricultural Reentry 

Task Force (ARTF), have been determined to require a review of their ethical conduct, and have 

received that review.

Data Requirements

None. 

References

The References below identify the human health risk assessment and occupational/residential 

exposure assessment documents that HED has produced for Trifloxysulfuron-sodium. 

Memoranda Relevant to Registration Review of Rimsulfuron

Author Barcode 

(DP#)

Date Title

S. Recore D408657 02/05/13 Trifloxysulfuron-Sodium: Review of Human Incidents

M. 

Doherty

D284104 09/24/03 Human Health Risk Assessment for the Section 3 

Registration of Trifloxysulfuron-sodium

on Almond, Citrus, Cotton, Sugarcane, Tomato, and Turf. 

PP# 1F06280.

M. 

Doherty

D352260 11/12/08 Trifloxysulfuron-Sodium: Human Health Risk Assessment 

for the Requested Use on Sports Fields and Residential 

Turfgrass.

S. Wang D353060 08/22/08 Trifloxysulfuron-Sodium: Occupational and Residential 

Exposure/Risk Assessment of Trifloxysulfuron-Sodium for 

Section 3 Registration of a New Use on Turf 

S. Wang D284482 09/20/03 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.

Attachments

Attachment 1. Chemical Identity Table

Attachment 2. International Residue Limit Status

Attachment 3. Trifloxysulfuron-sodium Summary of Use Products and Sites
Page 15 of 23

Attachment 4. Trifloxysulfuron-sodium Endpoint Selection Tables

Attachment 5. Trifloxysulfuron-sodium Toxicity Profile Tables
Page 16 of 23

Attachment 1. Chemical Identity Table

Chemical Identity

Common Name Trifloxysulfuron-sodium

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

2-pyridinesulfonamide sodium salt

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

pyridin-2-sulfonamide sodium salt

PC Code 119009

Chemical Abstracts Numbers 199119-58-9 (sodium salt); 290332-10-4 (sodium salt monohydrate);

145099-21-4 (free sulfonylurea)

Registration Review Case No. 7028

Chemical Class Sulfonylurea herbicide

Vapor Pressure <1 x 10-7

Pa at 25 C

Chemical Structure

N

O

CF3

S

N N

H

N

N OCH3

OCH3

O O

O

Na

+
Page 17 of 23

Attachment 2. International Residue Limit (IRL) Status 

International Residue Limits 

Trifloxysulfuron-sodium (PC Code 119009)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.591

trifloxysulfuron, N -[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]-3-(2,2,2-

trifluoroethoxy)-2-pyridinesulfonamide

None None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Almond, hulls 0.02

Almond 0.01

Fruit, citrus, Group 10 0.03

Cotton, undelinted seed 0.05

Cotton, gin byproducts 1.0

Sugarcane 0.01

Tomatoes 0.01

Completed: M. Negussie; 12/18/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Page 18 of 23

Attachment 3. Trifloxysulfuron-sodium Use Products and Sites Summary

Attachment 3. Use Patterns of Sec. 3/24C End-use Product Formulations of Trifloxysulfuron-Sodium.

Registered

products & 

Formul. Types 

% AI Use Sites and 

Applicable ORE Reviews 

Application 

equipment Comments 

100-1133 94 Technical Product N/A N/A

100-1132

WDG 

Formulation

75

Citrus, cotton (soil treatments)

Almonds, tomatoes, sugarcane, cotton (foliar 

treatments)

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.

Ground 

equipment, 

handheld 

equipment, 

backpack

do not apply 

within:

* 14 days of 

harvest 

(citrus)

* 3 days of 

harvest 

(almonds)

100-1134

WDG 

Formulation

75

Ornamentals

Turf (golf course, industrial use, and residential)

Trifloxysulfuron-Sodium: Occupational and Residential 

Exposure/Risk Assessment of Trifloxysulfuron-Sodium for 

Section 3 Registration of a New Use on Turf 

Ground 

equipment,

Handwand, 

backpack, 

handgun

No 

chemigation

100-1163

Granular 0.7

Cotton (soil treatment)

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.

Ground 

equipment

No aerial or 

chemigation

MS110004

WDG 

Formulation

75

Transplanted tomatoes

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.

Ground 

equipment, 

handheld 

equipment, 

backpack

Registered 

in MS
Page 19 of 23

Attachment 4. Trifloxysulfuron-sodium Endpoint Selection Tables

1

Toxicological Doses and Endpoints for Trifloxysulfuron-sodium for Use in Dietary and Non-Occupational 

Human Health Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

population)

NOAEL = 600 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF=1x

Total UF=100x

Acute RfD =6 

mg/kg/day

aPAD

= 6 mg/kg/day

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.

Acute Dietary

(Females 13-

49 years of 

age)

Developmental 

NOAEL = 50 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF=1x

Total UF=100x

Acute RfD =0.5 

mg/kg/day

aPAD

= 0.5mg/kg/day

Developmental Toxicity Study in 

Rabbits.

Developmental LOAEL=100 

mg/kg/day based on increased 

incidence of abnormally shaped hearts 

in fetuses.

Chronic 

Dietary (All 

Populations)

NOAEL=23.7 

mg/kg/day 

UFA= 10x

UFH=10x

FQPA SF=1x

Total UF=100x

Chronic RfD 

=0.237mg/kg/day

cPAD

= 

0.237mg/kg/day

Combined Chronic/CarcinogenicityRat

LOAEL = 99.3 mg/kg/day based on 

increased tubular atrophy in the 

kidneys of females. 

Incidental 

oral-ShortTerm (1-30 

days)

Offspring 

NOAEL = 79 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF=1x

Total UF=100x

Residential LOC 

for MOE = 100

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 

oralIntermediateTerm (1-6 

months)

NOAEL = 

45 mg/kg/day

UFA= 10x

UFH=10x

FQPA SF=1x

Total UF=100x

Residential 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.

DermalShort-Term 

(1-30 days) 

Oral study 

NOAEL= 50 

mg/kg/day

UFA=10x

UFH=10x

DAF=30 %

Occupational 

LOC for MOE = 

100

Developmental Toxicity Study in 

Rabbits. LOAEL = 100 mg/kg/day 

based on increased incidence of 

abnormally shaped hearts in fetuses.

DermalIntermediateTerm (1-6 

months)

Oral study 

NOAEL= 

45 mg/kg/day

UFA=10x

UFH=10x

DAF=30 %

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.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not Likely to be Carcinogenic to Humans”

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty 

factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among 

members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose 

(a = acute, c = chronic). RfD = reference dose. N/A = not applicable. 
Page 20 of 23

Summary of Toxicological Doses and Endpoints for Trifloxysulfuron for Use in Occupational Human Health 

Risk Assessments.

Exposure/

Scenario

Point of Departure Uncertainty 

Factors

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

DermalShort-Term 

(1-30 days) 

Oral study NOAEL= 

50 mg/kg/day

UFA=10x

UFH=10x

DAF=30 %

Occupational 

LOC for MOE 

= 100

Developmental Toxicity Study in 

Rabbits. LOAEL = 100 mg/kg/day 

based on increased incidence of 

abnormally shaped hearts in fetuses.

DermalIntermediateTerm (1-6 

months)

Oral study NOAEL= 

45 mg/kg/day

UFA=10x

UFH=10x

DAF=30 %

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 

Short-Term 

(1-30 days)

Oral study NOAEL= 

50 mg/kg/day

UFA=10x

UFH=10x

IAF=100%

Occupational 

LOC for MOE 

= 100

Developmental Toxicity Study in 

Rabbits. LOAEL = 100 mg/kg/day 

based on increased incidence of 

abnormally shaped hearts in fetuses.

Inhalation 

IntermediateTerm (1-6 

months)

Oral study NOAEL= 

45 mg/kg/day

UFA=10x

UFH=10x

IAF=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.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not Likely to be Carcinogenic to Humans”

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty 

factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among 

members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. 

IAF=inhalation absorption factor.

1

This endpoint selection table was taken directly from the last human health risk assessment (Memo, 

D352260, M. Doherty et al., 11/12/2008).
Page 21 of 23

Attachment 5 - Trifloxysulfuron-sodium – Toxicity Profiles

Table A4-1. 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

Table A4-2. 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 
Page 22 of 23

Table A4-2. Toxicity Profile of Trifloxysulfuron-sodium Technical Grade Active Ingredient.

Guideline 

No.

Study Type Results

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, 

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 NOAEL: 2000/600 mg/kg/day (M/F)
Page 23 of 23

Table A4-2. Toxicity Profile of Trifloxysulfuron-sodium Technical Grade Active Ingredient.

Guideline 

No.

Study Type Results

screening battery (rat) 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 excreted. 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 

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.

870.7800 Immunotoxicity The systemic NOAEL is 4000 ppm (1066.6 mg/kg/day); the LOAEL 

was not established (tested above the limit dose). No clinical signs of 

toxicity were observed and all mice survived to scheduled sacrifice. No 

treatment-related effects were found on body, liver, spleen, or thymus 

weights. Food intake was not affected by treatment.