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The critical effects resulting from oral administration with isoxaflutole were reported as ocular 

toxicity in rats, hepatotoxicity (including tumor formation), thyroid tumors in rats and mice, and 

hematotoxicity in dogs and mice. The liver and ocular toxicities are consistent with the proposed 

mode of action of isoxaflutole involving inhibition of the hepatic enzyme 4-

hydroxyphenylpyruvate dioxygenase (HPPD) that leads to the build-up of tyrosine in the blood 

and eyes, respectively.

Developmental toxicity was observed in rats and rabbits as growth retardations including delays 

in skeletal ossification, effects that have been observed with other HPPD inhibitors (e.g., 

pyrasulfotole). There was evidence of increased susceptibility in the rabbit study in the form of 

increased incidence of fetuses with 27th pre-sacral vertebrae at a dose much lower than those 

causing maternal deficits in body weight and food consumption. Neither the rat developmental 

study nor the rat 2-generation reproductive toxicity studies revealed any evidence of increased 

susceptibility. However, both adults and offspring in the 2-generation reproductive toxicity 

study exhibited ocular and liver toxicities seen in long-term studies.

Isoxaflutole was negative in a variety of genotoxicity screening assays. However, in 

carcinogenicity studies, isoxaflutole induced liver and thyroid tumors in rats and liver tumors in 

mice. Based on the tumor findings, the HED Carcinogenicity Peer Review Committee (CPRC; 

1997) classified isoxaflutole as “likely to be a human carcinogen.” 

Acute and chronic aggregate (food + dietary water) exposure and risk assessments were 

conducted using the Dietary Exposure Evaluation Model - Food Consumption Intake Database 

(DEEM-FCID , ver. 2.03). The acute and chronic analyses incorporated the drinking water 

estimates provided by the Environmental Fate and Effects Division (EFED). The estimated 

drinking water concentrations (EDWCs) were Tier 1 estimates for surface water using the FIRST 

model [Food Quality Protection Act (FQPA) Index Reservoir Screening Tool] for isoxaflutole 

and its degradate of concern, RPA 202248. EDWCs of 0.00739 ppm and 0.00186 ppm were 

used in the acute and chronic analysis, respectively. 

The acute analysis assumed DEEMTM (ver. 7.81) default processing factors, 100% crop treated 

(CT), and tolerance-level residues for all commodities. The resulting acute food plus water 

exposure estimates are not of concern to HED (≤100% acute population-adjusted dose (aPAD)) 

at the 95th percentile of the exposure distribution for all population subgroups of interest; the 

resulting acute exposure estimate for females 13 to 49 years old (the subgroup with the greatest 

risk) was 2.3% of the aPAD at the 95th percentile of the exposure. 

The chronic and cancer analyses assumed DEEMTM (ver. 7.81) default processing factors, 100% 

CT, and tolerance-level residues for all commodities. The chronic and cancer analyses also 

incorporated the drinking water estimates provided by EFED (see above). The resulting chronic 

and cancer risk estimates are not of concern to HED. The most highly exposed population was 

all infants (<1 year old) utilizing 9.1% of the chronic PAD (cPAD). The cancer risk for the 

general U.S. population was 9 x 10-7.

The residue chemistry database is sufficient to support the current registrations. The following 

data requirement remains outstanding: successful petition method validation (PMV) of the 

proposed plant enforcement method. 

There are no established Mexican or Codex maximum residue limits (MRLs) for residues of 

isoxaflutole. Therefore, issues of compatibility with respect to U.S. tolerances and Codex MRLs 
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do not exist. However, as the Canadian tolerance for corn grain contains an additional 

metabolite (2-metylsulfonyl-4-trifluorometyl benzoic acid), harmonization is not possible at this 

time. In addition, Canadian MRLs are established for livestock commodities.

There is sufficient information available to assess occupational exposure to isoxaflutole. All of 

the occupational exposure scenarios for the registered uses of isoxaflutole have been assessed 

adequately, except for the occupational handler cancer risks from the dry-flowable (DF) 

formulation registered on corn. This assessment has been conducted in the past, but needs to be 

updated using current HED assumptions. In addition, based on the Agency's current practices, a 

quantitative occupational post-application inhalation exposure assessment has not been 

performed for isoxaflutole; however, if new policies or procedures are put into place, the Agency 

may revisit the need for a quantitative occupational post-application inhalation exposure 

assessment. 

Introduction

Isoxaflutole, an isoxazole herbicide (Group 27) for control of broadleaf and grass weeds, is 

registered by Bayer CropScience for a Section 3 use as a pre-emergent or early post-emergence

broadcast treatment to field corn (the only registered food use); and a crop-destruct Section 5 

EUP use as a pre-plant, pre-emergent, or early post-emergent broadcast treatment to isoxaflutoletolerant soybeans. The registered products include the SC formulations Balance®

PRO (EPA 

Reg. No. 264-600), Balance®FLEXX (EPA Reg. No. 264-1067), and Corvus®(EPA Reg. No. 

264-1066); containing isoxaflutole at concentrations of 4.0 lb ai/gal, 2.0 lb ai/gal, and 1.88 lb 

ai/gal, respectively. Use on corn is limited to a single pre-emergent or early post-emergence 

application at a maximum rate of 0.094 lb ai/A. There are no registered or proposed residential 

uses.

HED recently evaluated a crop-destruct EUP for use on soybeans (D370958, G. Kramer, et al.; 

09-MAR-2010). A Section 3 request for use on soybeans is currently under evaluation.

The nature of the residue in corn is understood, based on metabolism studies with corn treated 

with isoxaflutole. The residues of concern for both the tolerance expression and risk assessment 

are isoxaflutole and RPA 202248. The nature of the residue in livestock is understood based on 

metabolism studies with goats and hens. The residues of concern in livestock for tolerance 

enforcement are isoxaflutole and RPA 202248; for risk assessment, the residues of concern are 

isoxaflutole, RPA 202248, RPA 205834, and RPA 207048. The residue chemistry database is 

sufficient to support the current registrations. 

Data needs and risk assessment updates required under registration review for isoxaflutole are as 

follows:

Toxicology:

The toxicity endpoint/dose selection along with the FQPA Safety Factor (SF) will need to 

be re-evaluated according to current policy.

Residue Chemistry:

Successful PMV of the proposed plant enforcement method.

The tolerance expression for isoxaflutole residues needs to be updated to reflect current 

Agency policy: “Tolerances are established for residues of the herbicide isoxaflutole, 
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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 the sum of isoxaflutole ((5-cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-

(trifluoromethyl)phenyl]methanone) and its metabolite 1-(2-methylsulfonyl-4-

trifluoromethylphenyl)-2-cyano-3-cyclopropylpropan-1,3-dione, calculated as the 

stoichiometric equivalent of isoxaflutole, in or on the following commodities:”

Dietary Exposure:

A new dietary risk assessment incorporating updated EDWCs may be required.

Occupational Exposure:

A revised occupational exposure assessment. 

Hazard Identification/Toxicology

Isoxaflutole is an isoxazole herbicide registered for control of broadleaf and grass weeds in corn. 

In acute toxicity studies, isoxaflutole was minimally toxic by the oral (Category IV), dermal 

(Category III) and inhalation (Category IV) routes of exposure. It was not a dermal irritant, an 

eye irritant, or a dermal sensitizer. 

Following oral administration in the rat, radiolabeled isoxaflutole was rapidly and extensively 

absorbed and metabolized. No sex-related differences in metabolism were observed. 

Elimination was dose-dependent, with the majority of the radiolabel being eliminated in the first 

24 and 48 hrs for the low (1 mg/kg) and high (100 mg/kg) dose, respectively. Very low levels of 

radioactivity were observed in tissues at 168 hours post-dosing. Elimination half-lives were 

similar between the low- and high-dose groups, with an estimated mean blood half-life of 60 hrs.

The critical effects resulting from oral administration with isoxaflutole were reported as ocular 

toxicity in rats, hepatotoxicity (including tumor formation), thyroid tumors in rats and mice, and 

hematotoxicity in dogs and mice. The liver and ocular toxicities are consistent with the proposed 

mode of action of isoxaflutole involving inhibition of the hepatic enzyme HPPD that leads to the 

build-up of tyrosine in the blood and eyes, respectively.

Developmental toxicity was observed in rats and rabbits as growth retardations including delays 

in skeletal ossification, effects that have been observed with other HPPD inhibitors (e.g., 

pyrasulfotole). There was evidence of increased susceptibility in the rabbit study in the form of 

increased incidence of fetuses with 27th pre-sacral vertebrae at a dose much lower than those 

causing maternal deficits in body weight and food consumption. Neither the rat developmental 

study nor the rat 2-generation reproductive toxicity studies revealed any evidence of increased 

susceptibility. However, both adults and offspring in the 2-generation reproductive toxicity 

study exhibited ocular and liver toxicities seen in long-term studies.

In acute and subchronic neurotoxicity studies in adult rats, mild changes in functional 

observation battery (FOB) parameters (grip strength and/or landing foot splay) were observed. 

However, such effects were not observed in either pregnant animals or offspring in a 

developmental-neurotoxicity study (DNT) study in rats. In both maternal animals and offspring, 

body-weight changes and/or food consumption were the primary effects noted and at the same 

dose tested. Decreased brain weights were observed in offspring on PND 11 at the high dose 
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only, but not at a later time point, which is an indicator of a developmental delay and/or a 

secondary effect of the decreased body weight also observed in the offspring. Although 

morphometric analyses were not performed in the DNT study, there were no effects on pup 

swimming ability, learning, memory, motor activity, or auditory startle response at any dose, nor 

was there any evidence of neuropathology at any dose. As a result, the missing morphometric 

measurements, while required, are unlikely to affect the tentative LOAEL of the study (highest 

dose tested). 

A 21-day dermal toxicity study with isoxaflutole showed that a dose as high as 1000 mg/kg 

failed to induce any type of dermal or systemic toxicity.

Isoxaflutole was negative in a variety of genotoxicity screening assays. However, in 

carcinogenicity studies, isoxaflutole induced liver and thyroid tumors in rats and liver tumors in 

mice. Based on the tumor findings, the HED CPRC (1997) classified isoxaflutole as “likely to 

be a human carcinogen.” 

In the last risk assessment (D370958, G. Kramer, et al.; 09-MAR-2010), the only database 

deficiency noted was a guideline immunotoxicity study as part of new toxicity data requirements 

in the 40 CFR Part 158 for conventional pesticide registration. Since then, an immunotoxicity 

study has been submitted and reviewed by the Agency. The results of this study indicate that 

there were no immunosuppressive effects following repeated daily dosing with isoxaflutole up to 

the highest dose tested of 279 mg/kg/day. Thus, the immune system does not appear to be a 

target for isoxaflutole.

Endocrine Disruption

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 its 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), isoxaflutole 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. 
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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. Isoxaflutole 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 callins, requiring the submission of EDSP screening assays for isoxaflutole. 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/.

Inhalation Toxicity Study

Based on the available toxicity database and the Agency's current practices, the inhalation risk 

for isoxaflutole was assessed using an oral toxicity study. The Agency sought expert advice and 

input on issues related to this route-to-route extrapolation approach (i.e., the use of oral toxicity 

studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide 

Act (FIFRA) 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 and may, as appropriate, re-examine and develop new 

policies and procedures for conducting inhalation risk assessments, including route-to-route

extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may 

revisit the need for an inhalation toxicity study for isoxaflutole and/or a re-examination of the 

inhalation toxicity risk assessment.

Conclusions

The toxicity database for isoxaflutole is adequate to support existing registrations and 

registration review. The toxicity endpoint/dose selection along with the FQPA SF will need to 

be re-evaluated according to current policy.

Residue Chemistry

The nature of the residues in corn is understood, based on metabolism studies with corn treated 

with isoxaflutole. The HED Residues of Concern Knowledgebase Subcommittee (ROCKS)

determined that the residues of concern for both the tolerance expression and risk assessment are 

isoxaflutole and RPA 202248 (DP# 354076, 7/10/08, R. Daiss). The nature of the residue in 

livestock is understood based on metabolism studies with goats and hens. The residues of 

concern in livestock for tolerance enforcement are isoxaflutole and RPA 202248; for risk 

assessment, the residues of concern are isoxaflutole, RPA 202248, RPA 205834, and RPA 

207048 (DP# 354076, 7/10/08, R. Daiss). 

A liquid chromatography with tandem mass spectrometry (LC/MS/MS) method is available for 

the enforcement of the proposed tolerances for corn commodities. The method was forwarded to 

Agency chemists at Analytical Chemistry Laboratory/Biological and Economics Analysis 

Division (ACL/BEAD) for a petition method validation (PMV).

Adequate crop field trial data are available to support the proposed tolerances. Quantifiable 

residues of isoxaflutole and RPA 202248 analytes were found only in forage samples from a 

single trial (out of 20 trials). Based on the results of these trials, the established tolerances for 

field corn grain, forage, and stover are appropriate.
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Adequate livestock feeding studies have been submitted. The livestock feeding study data with 

the estimated maximum dietary burdens indicate that tolerances are not needed for the combined 

residues of parent and RPA 202248 in meat, milk, poultry, and eggs. 

Adequate confined and field rotational crop studies have been submitted; the residues of concern 

in rotational crops are isoxaflutole and its metabolite RPA 202248. These data indicated that 

plantback intervals (PBIs) of 4 months for wheat and 6 months for all other crops are appropriate 

for isoxaflutole; no rotational crop tolerances are required. 

Conclusions

The qualitative nature of isoxaflutole residues in corn, rotational crops, and livestock is 

adequately understood. The residues of concern for both the tolerance expression and risk 

assessment are isoxaflutole and RPA 202248. The nature of the residue in livestock is 

understood based on metabolism studies with goats and hens. The residues of concern in 

livestock for tolerance enforcement are isoxaflutole and RPA 202248; for risk assessment, the 

residues of concern are isoxaflutole, RPA 202248, RPA 205834, and RPA 207048. The residue 

chemistry database is sufficient to support the current registrations. The following data 

requirement remains outstanding: successful PMV of the proposed plant enforcement method. 

Dietary Exposure

The most recent chronic dietary-exposure assessment was performed in conjunction with the 

March 2010 human-health risk assessment conducted by HED (D370958, G. Kramer, et al.; 09-

MAR-2010). Dietary risk assessments were conducted using DEEM-FCID , ver. 2.03, which

incorporates consumption data from the United States Department of Agriculture (USDA) 

Continuing Surveys of Food Intakes by Individuals (CSFII; 1994-1996 and 1998). The acute 

analysis assumed DEEMTM (ver. 7.81) default processing factors, 100% CT, and tolerance-level 

residues for all commodities. The resulting acute food plus water exposure estimates are not of 

concern to HED (≤100% aPAD) at the 95th percentile of the exposure distribution for all

population subgroups of interest, the resulting acute exposure estimate for females 13 to 49 years 

old (the subgroup with the greatest risk) was 2.3% of the aPAD at the 95th percentile of the 

exposure. The chronic analysis assumed DEEMTM (ver. 7.81) default processing factors, 100% 

CT, and tolerance-level residues for all commodities. The resulting chronic and cancer risk

estimates are not of concern to HED. The most highly exposed population was all infants (<1 

year old) utilizing 9.1% of the cPAD. The cancer analysis assumed DEEMTM (ver. 7.81) default 

processing factors, 100% CT, and tolerance-level residues for all commodities. The resulting 

cancer risk estimate, 9 x 10-7for the general U.S. population, is not of concern to HED. 

The HED Residues of Concern Knowledgebase Subcommittee (ROCKS) determined that the 

residues of concern for drinking water are isoxaflutole and RPA 202248 (DP# 354076, 7/10/08, 

R. Daiss). Drinking water residues were incorporated directly into the acute and chronic dietary 

analyses (“water, direct, all sources” and “water, indirect, all sources”) and were provided by 

EFED (DP# 370959; 1/29/2010, W. Shaughnessy). The EDWCs were Tier 1 estimates for 

ground water using the SCI-GROW model and surface water using the FIRST model for 

isoxaflutole and RPA 202248. The models utilized an application rate of 0.141 lbs. ai/A with a 

single application to corn per season (highest previously registered/proposed use rate). HED 

notes that the maximum use rate has been subsequently lowered to 0.094 lbs. ai/A.
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Conclusions

The dietary-exposure database is adequate to support the existing registrations. However, a new 

dietary assessment may be required during Registration Review to incorporate potential changes 

to the isoxaflutole estimated drinking water concentrations.

Residential Exposure

There are currently no registered residential uses of isoxaflutole. Therefore, residential handler 

and post-application exposures have not been assessed. 

Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative residential bystander post-application

inhalation exposure assessment was not performed for isoxaflutole at this time. However, 

volatilization of pesticides may be a potential source of post-application inhalation exposure to 

individuals nearby to pesticide applications. The Agency sought expert advice and input on 

issues related to volatilization of pesticides from its FIFRA 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 and may, as appropriate, develop policies and procedures, 

to identify the need for and, subsequently, the way to incorporate 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 post-application inhalation exposure assessment 

for isoxaflutole.

Spray Drift 

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 isoxaflutole. 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 (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical-by-chemical basis, 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 database 

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 with specific products with significant risks 

associated with drift.

Conclusions

Residential handler and post-application exposures are not permitted by the label and have not 

been previously assessed, nor are they expected. Because there are currently no registered 

residential uses, an assessment is not required at this time. 
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Aggregate Risk Assessment

In the most recent risk assessment of isoxaflutole (D370958, G. Kramer, et al.; 09-MAR-2010), 

the dietary exposure analysis represented the aggregate chronic risk assessment because it 

included drinking water estimates. Since there are no registered or proposed uses that result in 

residential exposures, only chronic aggregate exposure assessments considering exposure from 

food and water are required. 

Conclusions

A new aggregate risk assessment may be required during Registration Review to incorporate 

potential changes to the isoxaflutole EDWCs. 

Occupational Exposure

Isoxaflutole is registered for a Section 3 use as a pre-plant or pre-emergent broadcast treatment 

to field corn; and a crop-destruct Section 5 EUP use as a pre-plant, pre-emergent, or early postemergent broadcast treatment to isoxaflutole-tolerant soybeans. Previous occupational exposure 

assessments addressing both cancer and non-cancer risks have been conducted for field corn 

(Memos, T. Keigwin, 10/21/97, D238846; 11/26/97, D241075) and isoxaflutole-tolerant 

soybeans (Memo, A. Nowotarski, 3/9/10; D373091).

Occupational Handlers: HED has determined that there is potential handler exposure to 

isoxaflutole from the following scenarios: 1) mixing and loading DF formulations in support of 

groundboom applications; 2) mixing and loading liquid formulations in support of groundboom 

operations; and 3) applying liquids using open-cab groundboom equipment. HED has completed 

cancer and non-cancer handler assessments for the scenarios above (see Tables A4.2 and A4.3 in 

the attachments). It should be noted that both DF and liquid formulations are registered for the 

corn use; however, only the DF formulation was assessed in previous risk assessments. The 

registered soybean use is for a liquid formulation and has been assessed at the same rate as that 

registered for the corn use. Therefore, the assessment for the soybean use covers the corn use. 

Non-cancer: As no chemical-specific data were available with which to assess potential 

exposure to pesticide handlers, the occupational handler non-cancer assessments were based 

primarily on surrogate unit exposures from the Pesticide Handlers Exposure Database (PHED), 

the maximum application rates allowed on registered labels and assuming default maximum area 

treated per day for specific crops. Handler's exposure and risk were calculated at the following 

levels of mitigation: baseline (long pants, a long-sleeved shirt, no chemical-resistant gloves, and 

no respirator) and with personal-protective equipment (PPE; baseline clothing with chemicalresistant gloves, when necessary). Provided that commercial pesticide handlers use label 

prescribed PPE (i.e., long pants, long sleeved shirt, shoes + socks and the respective protective 

gloves), all assessed MOEs were not of concern to HED (MOE ≥300). 

Cancer: The occupational handler cancer risk estimates resulting from exposures to isoxaflutole 

were calculated using a linear low-dose extrapolation approach (Q1*). For the field corn use, 

occupational handler scenarios were assessed for Pesticide Control Officers (PCOs) and 

individual farmers, assuming different acres treated/day for each. The assumptions used in the 

exposure and risk calculations for the corn use are different from current HED assumptions and; 

therefore, the cancer assessment for the DF formulation would need to be re-assessed. As with 
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the non-cancer assessment, the liquid formulation corn use is covered by the assessment that was 

conducted for the soybean use. 

For the soybean use, occupational handler exposure scenarios were assessed for individuals 

employed by multiple establishments (i.e., commercial or migratory farmworkers) and were 

assumed to be exposed for 30 days per year. Provided that commercial pesticide handlers and 

farmers use label prescribed PPE (i.e., long pants, long-sleeved shirt, shoes + socks and the 

respective protective gloves), estimated cancer risks are below 10-6.

Occupational Post-Application: For the corn use, an occupational postapplication dermal 

assessment was not performed. The past risk assessments state that considering the labeled use 

pattern (pre-plant or pre-emergent), post-application exposure is not expected because no corn 

foliage is present. For the soybean use, the current label also limits the timing of applications to 

pre-plant, pre-emergence or pre-bloom (up to, but not including first bloom); therefore, postapplication cancer and non-cancer dermal assessments were conducted for those activities assumed 

most likely to occur when minimal foliage is present.

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

exposure assessment has not been performed for isoxaflutole. 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 FIFRA 

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 postapplication 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 isoxaflutole.

Non-cancer: For the non-cancer dermal risk from use on soybeans, no chemical-specific data 

were available with which to estimate dermal post-application exposure of agricultural workers 

to dislodgeable residues of isoxaflutole. Therefore, post-application worker exposure was 

estimated using a default HED procedure that assumes 20% of the application rate is available as 

dislodgeable foliar residue (DFR) on the day of treatment and that there is 10% dissipation each 

day following application. The calculated residues were then used with default transfer 

coefficients taken from the HED Science Advisory Council for Exposure (ExpoSAC) Policy 

003.1, which lists a number of possible post-application agricultural activities relative to some of 

the subject crops, to estimate potential pesticide exposure to agricultural workers. HED has 

determined that short- and intermediate-term risk estimates are not of concern (i.e., MOEs ≥300) 

on the day of treatment (i.e., Day 0) for all post-application exposure activities associated with 

the soybean use (see Table A4.4 in the attachments).

Cancer: Occupational post-application dermal exposure scenarios for the soybean use were 

assessed for individuals employed by multiple establishments (i.e., commercial or migratory 

farmworkers) and were assumed to be exposed 30 days per year. DFRs were estimated using the 

method described above (assuming 20% of the active ingredient is available initially and 
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dissipation of 10% per day thereafter). HED used the average residue over 30 days to estimate 

cancer risk. Estimated cancer risks are below 10-6(see Table A4.5 in the attachments).

Conclusions

There is sufficient information available to assess occupational exposure to isoxaflutole. All of 

the occupational exposure scenarios for the registered uses of isoxaflutole have been assessed 

adequately, except for the occupational handler cancer risks from the DF formulation registered 

on corn. This assessment has been conducted in the past, but needs to be updated using current 

HED assumptions. In addition, based on the Agency's current practices, a quantitative 

occupational post-application inhalation exposure assessment has not been performed for 

isoxaflutole; however, if new policies or procedures are put into place, the Agency may revisit 

the need for a quantitative occupational post-application inhalation exposure assessment. 

Public Health and Pesticide Epidemiology Data

For this evaluation, the OPP Incident Data System (IDS) was utilized for pesticide incident data 

on the active ingredient isoxaflutole. The purpose of the database search is to identify potential 

patterns on the frequency and severity of the health effects attributed to isoxaflutole exposure. 

The IDS includes reports of alleged human health incidents from various sources, including 

mandatory FIFRA Section 6 (a) (2) reports from registrants, other federal and state health and 

environmental agencies, and individual consumers. Since 1992, OPP has compiled these reports 

in IDS. IDS contain reports from across the U.S. and most incidents have all relevant product 

information recorded. Reports submitted to the IDS represent anecdotal reports or allegations 

only, unless otherwise stated in the report. The Agricultural Health Study (AHS) is a highquality, prospective epidemiology study evaluating the link between pesticide use and various 

health outcomes including cancer. The AHS includes private and commercial pesticide 

applicators and their spouses. If there are AHS findings relevant to a particular pesticide going 

through registration review, then the Agency will ensure they are considered in the problem 

formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk 

assessment phase of the process. The AHS includes information on use of 50 different pesticide 

active ingredients commonly used in agriculture.

IDS records incidents resulting in higher severity outcomes in more detail, in a module called the 

Main IDS module. This system stores incident data for death, major and moderate incidents, and 

it includes more details about the location, date, and nature of the incident. Main IDS incidents 

involving only one pesticide are considered to provide more certain information about the 

potential effects of exposure from the pesticide, and therefore, if present, these incidents are 

listed in a table at the end of this report. Additionally, since higher-severity incidents are 

generally of greater concern, incidents involving death and major outcomes would also include a 

narrative summary. The less severe human incidents (minor, unknown, or no effects outcomes) 

are reported by registrants as counts called aggregate summaries and are recorded in separate 

module called Aggregate IDS. In Aggregate IDS, from January 1, 2002 to May 27, 2010, there 

are three cases reported for isoxaflutole. Because it falls within the categories reported as counts

(which includes minor, unknown, or no effects), there is no unique report that provides details 

about the incident and single chemical incidents are not distinguished from multiple chemical 

incidents; however, a high frequency of incidents indicates there is a high potential for exposure 

and vice versa. For isoxaflutole, there appears to be a low potential for exposure. For the Main 

IDS, from January 1, 2002 to November 30, 2010, there are no cases reported that involve the 

active ingredient isoxaflutole. 
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Isoxaflutole is included in AHS, but it is part of phase III and those data have not been published 

yet.

Based on the lack of incident cases reported to IDS, 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 risk 

assessment.

Tolerance Assessment and International Harmonization

U.S. permanent tolerances (listed in 40 CFR 180.537) and MRLs are summarized in Attachment 

6. There are no established Mexican or Codex MRLs for residues of isoxaflutole. Therefore, 

issues of compatibility with respect to U.S. tolerances and Codex MRLs do not exist. However, 

as the Canadian tolerance for corn grain contains an additional metabolite (2-metylsulfonyl-4-

trifluorometyl benzoic acid), harmonization is not possible at this time. In addition, Canadian 

MRLs are established for livestock commodities.

Environmental Justice

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

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.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who may be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

Human Studies

Past isoxaflutole risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and inhalation 

exposure. Many such studies, involving exposure to many different pesticides, comprise 

generic pesticide exposure databases such as PHED, the Outdoor Residential Exposure Task 

Force (ORETF) Database, and the Agricultural Reentry Task Force (ARTF) Database. EPA 

has reviewed all the studies supporting these multi-pesticide generic exposure databases, and 

has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is 

no regulatory barrier to continued reliance on these studies.
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Data Requirements

Toxicology:

The toxicity endpoint/dose selection along with the FQPA SF will need to be reevaluated according to current policy.

Residue Chemistry:

Successful PMV of the proposed plant enforcement method.

The tolerance expression for isoxaflutole residues needs to be updated to reflect current 

Agency policy: “Tolerances are established for residues of the herbicide isoxaflutole, 

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 the sum of isoxaflutole ((5-cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-

(trifluoromethyl)phenyl]methanone) and its metabolite 1-(2-methylsulfonyl-4-

trifluoromethylphenyl)-2-cyano-3-cyclopropylpropan-1,3-dione, calculated as the 

stoichiometric equivalent of isoxaflutole, in or on the following commodities:”

Dietary Exposure:

A new dietary risk assessment incorporating updated EDWCs may be required.

Occupational Exposure:

A revised occupational exposure assessment. 

References

Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

G. Kramer, et al. 370958 09-MAR-2010

Isoxaflutole. Crop-Destruct Experimental Use Permit 

(EUP) for Use on Soybeans. Human-Health Risk 

Assessment.

G. Kramer 373360 26-FEB-2010

Isoxaflutole. Crop-Destruct Experimental Use Permit 

(EUP) for Use on Soybeans. Acute and Chronic Dietary 

Exposure and Risk Assessments.

W. Shaughnessy 370959 29-JAN-2010 Experimental Use Permit Drinking Water Assessment of 

Isoxaflutole for Use on Soybeans.

G. Kramer 354799 01-AUG-2008 Isoxaflutole in/on Corn. Request for Petition Method 

Validation (PMV).

G. Kramer 349689 22-JUL-2008

Isoxaflutole. Petition to Remove the Benzoic Acid 

Metabolite (RPA 203328) From the Tolerance Expression. 

Summary of Analytical Chemistry and Residue Data.

R. Daiss 354076 10-JUL-2008 Isoxaflutole. Report of the Residues of Concern 

Knowledgebase Subcommittee (ROCKS).

G. Kramer 340598 11-APR-2008

Isoxaflutole. Application for Registration of Two New 

Products for Use on Corn: SC 465 Herbicide and SC 480 

Herbicide. Summary of Analytical Chemistry and Residue 

Data.

A. Nowotarski 373091 09-MAR-2010 Isoxaflutole: Occupational and Residential Exposure/Risk 

Assessment for Proposed Experimental Use on Soybeans.

T. Keigwin 238845 21-OCT-97 Occupational Exposure Assessment for the Use of 

Isoxaflutole (Balance) on Corn.

T. Keigwin 241075 26-NOV-97 Correction to Occupational Exposure Assessment for the 

Use of Isoxaflutole (Balance) on Corn.
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Table 1. Memoranda Relevant to Registration Review.

Author Barcode Date Title

B. Madden 243997 27-JUL-98 Isoxaflutole – 123000: Revised Health Effects Division 

Risk Characterization Document for the First Food Use of 

Isoxaflutole in/on Corn (6F4664).

Attachments:

Attachment 1: Chemical Identity Table.

Attachment 2: Isoxaflutole Endpoint Selection Tables.

Attachment 3: Exposure Potential for Adult and Child Aggregate Risk Estimates.

Attachment 4: Occupational Use Patterns/Exposure Scenarios for Isoxaflutole.

Attachment 5: Isoxaflutole International Residue Limit Status Sheet. 

cc: J. Tyler (RAB1), G. Kramer (RAB1), C. Rodriguez (RAB1)

RDI: RAB1 (3/9/11), J. Fowle (3/16/11)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Attachment 1: Chemical Identity Table.

Isoxaflutole Nomenclature.

Chemical structure of parent

F

F

F

S

O O

CH3

O

O

N

Common name Isoxaflutole

Company experimental name RPA 201772; AE B197278

IUPAC name 5-cyclopropyl-4-(2-mesyl-4-trifluoromethylbenzoyl)isoxazole

CAS name (5-cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-

(trifluoromethyl)phenyl]methanone

CAS registry number 141112-29-0

End-use product (EP) BALANCE®PRO, EPA Reg. No. 264-600

Chemical structure of 

regulated metabolite

Common name Isoxaflutole diketonitrile; RPA 202248

Chemical name 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propane1,3-dione

Chemical structure of 

metabolite included in risk 

assessment for livestock 

commodities

Common name RPA 205834

Chemical structure of 

metabolite included in risk 

assessment for livestock 

commodities

Common name RPA 207048

F

F

F

S

O O

CH3

O O

CN

S

O O

CH3

F

F

F

O O

H2N

S

O O

CH3

F

F

F

O O

HO
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Attachment 2: Isoxaflutole Endpoint Selection Tables.

Table A2.1. Summary of Toxicological Doses and Endpoints for Isoxaflutole in the 2010 Dietary HumanHealth Risk Assessment.

Exposure Scenario

Point of 

Departure

Uncertainty 

Factors

LOC for Risk 

Assessment Study and Toxicological Effects

Acute Dietary -

females 13-49 years 

old

LOAEL = 5 

mg/kg/day

UFA = 10X

UFH = 10X

UFFQPA = 3X

(includes 

UFL)

aRfD = aPAD = 

0.02 mg/kg

Prenatal developmental toxicity 

(rabbit).

Offspring LOAEL = 5 mg/kg/day 

based on increased incidence of 

fetuses with 27th pre-sacral 

vertebrae.

Acute Dietary -

general population, 

including infants and 

children

NOAEL = 125 

mg/kg

UFA = 10X

UFH = 10X

UFFQPA = 1X

aRfD = aPAD = 

1.25 mg/kg

Acute neurotoxicity (rat).

LOAEL = 500 mg/kg based on 

significant decreases in hind limb 

grip strength and landing foot 

splay on day 15.

Chronic Dietary

NOAEL = 2

mg/kg/day

UFA = 10X

UFH = 10X

UFFQPA = 1X

cRfD = cPAD = 

0.02 mg/kg/day

Combined chronic 

toxicity/carcinogenicity (rat).

LOAEL = 20 mg/kg/day based on 

liver, thyroid, ocular, and nervous 

system toxicity (M) and liver 

toxicity (F).

Cancer

Q1* (mg/kg/day)-1of 1.14 x 10-2from the male CD-1 mouse liver for the linear low-dose 

extrapolation based on statistically significant increases in liver tumors in both sexes of 

mice and rats.

Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential variation in 

sensitivity among members of the human population (intraspecies), UFL = extrapolation due to the use of a LOAEL in the 

absence of a NOAEL, UFFQPA = FQPA Safety Factor, NOAEL = no-observed adverse-effect level, LOAEL = lowest-observed 

adverse-effect level, RfD = reference dose (a = acute, c = chronic).

Table A2.2. Summary of Toxicological Doses and Endpoints for Isoxaflutole in the 2010 Occupational 

Human-Health Risk Assessment.

Exposure Scenario

Point of 

Departure

Uncertainty 

Factors

RfD, LOC for 

Risk Assessment Study and Toxicological Effects

Dermal

Short- and 

Intermediate- Term 

(1-30 days and 1-6 

months)

LOAEL = 5 

mg/kg/day

Dermalabsorption 

factor = 3.5%

UFA = 10X

UFH = 10X

UFL = 3X

Occupational 

LOC for MOE 

<300

Prenatal developmental toxicity 

(rabbit).

Offspring LOAEL = 5 mg/kg/day 

based on increased incidence of 

fetuses with 27th pre-sacral 

vertebrae.

Inhalation

Short- and 

Intermediate- Term 

(1-30 days and 1-6 

months)

LOAEL = 5 

mg/kg/day

100% 

inhalation 

assumed

UFA = 10X

UFH = 10X

UFL = 3X

Occupational 

LOC for MOE 

<300

Prenatal developmental toxicity 

(rabbit).

Offspring LOAEL = 5 mg/kg/day 

based on increased incidence of 

fetuses with 27th pre-sacral 

vertebrae.

Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential variation in 

sensitivity among members of the human population (intraspecies), UFL = extrapolation due to the use of a LOAEL in the 

absence of a NOAEL, UFFQPA = FQPA Safety Factor, NOAEL = no-observed adverse-effect level, LOAEL = lowest-observed 

adverse-effect level, LOC = level of concern, MOE = margin of exposure.
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Attachment 3: Exposure Potential for Adult and Child Aggregate Risk Estimates.

(From D370958, G. Kramer, et. al; 09-MAR-2010)

Summary of Dietary (Food and Drinking Water) Exposure and Risk for Isoxaflutole.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.000442 <1 0.000077 3.8 0.000077 9 x 10-7

All Infants (<1 year old) 0.001555 1.2 0.000181 9.1

N/A N/A

Children 1-2 years old 0.000736 <1 0.000132 6.6

Children 3-5 years old 0.000680 <1 0.000142 7.1

Children 6-12 years old 0.000475 <1 0.000105 5.3

Youth 13-19 years old 0.000375 <1 0.000082 4.1

Adults 20-49 years old 0.000391 <1 0.000067 3.4

Adults 50+ years old 0.000342 <1 0.000055 2.7

Females 13-49 years old 0.000392 2.3 0.000067 3.4

*The values for the highest risk population for each type of risk assessment are bolded.
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Attachment 4: Occupational Use Patterns/Exposure Scenarios for Isoxaflutole.

Table A4.1. Summary of Occupational Uses for Isoxaflutole.

Use Sites Product 

Type(s)1

Application 

Equipment Application Type Timing

Maximum Single 

Application Rate (lb 

ai/A)

REI

Section 3 Registrations

Field Corn

EC ground

burndown, soil band, 

soil broadcast, soil 

treatment

pre-plant, preemergence

0.094 12 hours

DF/WDG ground

burndown, soil band, 

soil broadcast, soil 

incorporated, soil 

treatment

pre-plant, preemergence

0.14 12 hours

Section 5 Registration

Isoxaflutole-tolerant 

Soybeans SC ground Groundboom

pre-plant, preemergence, 

early postemergent

0.094 12 hours

1. DF = dry flowable, WDG = water dispersible granules, EC = emulsifiable concentrate, SC = soluble concentrate.

Table A4.2. Summary of Representative Occupational Handler Non-Cancer Exposure Scenarios and Risks for Isoxaflutole1.

Exposure Scenario Assessed DP#

App. 

Rate

(lb ai/A)

Daily 

Amount 

Treated

Unit Exposure

(mg/lb ai)

Short- and IntermediateTerm MOE

Inhalation Dermal Inhalation Dermal

Field Corn

Mixer/Loader Open pour – water 

dispersible granule 

D238846 0.2

farmer 

105

PCO2200

0.00077 SLNG 

0.0633

farmer 4500

PCO 2500

Applicator Applicator –

groundboom – open cab 0.00074 SLNG 0.014 farmer 12000PCO 6100

Mixer/Loader

/Applicator

Open pour – DF/WDG -

groundboom – open cab 0.015 0.077 farmer 3300

Isoxaflutole-Tolerant Soybeans

Mixer/Loader Open pour – liquid –

groundboom D373091 0.094 200

0.0012

SLNG 2.9

SLWG 

0.023

13,000

SLNG 130

SLWG 

20,000

Applicator Applicator –

groundboom – open cab 0.00074 SLNG 0.014 22,000 33,000

1. SLNG = Dermal Single Layer Work Clothing No Gloves; SLWG = Dermal Single Layer Work Clothing With Gloves.

2. PCO = Pesticide Control Officer.
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Table A4.3. Summary of Representative Occupational Handler Cancer Exposure Scenarios and Risks for Isoxaflutole.

Exposure Scenario Assessed DP#

App. 

Rate

(lb ai/A)

Daily 

Amount 

Treated

Dose1

(mg/kg/day)

Combined 

ADD2

(mg/kg/day)

LADD3

(mg/kg/day)

Cancer

Risk4

Inhalation Dermal

Field Corn

Mixer/Loader Open pour – water 

dispersible granule 

D238846 0.2 farmer 105

PCO2200

- -

farmer 1.1E03

PCO

2.0E-03

farmer

3.1E-06

PCO

1.8E-05

farmer 

3.5E-08

PCO

2.0E-07

Applicator

Applicator –

groundboom – open 

cab

- -

farmer 4.3E04

PCO

8.2E-04

farmer

1.3E-06

PCO

7.2E-06

farmer 

1.5E-08

PCO

8.2E-08

Mixer/Loader/

Applicator

Open pour –

DF/WDG -

groundboom – open 

cab

- -

farmer 1.5E03farmer

4.4E-06

farmer 

5.0E-08

Isoxaflutole-Tolerant Soybeans

Mixer/Loader Open pour – liquid 

– groundboom

D373091 0.094 200

0.0003223

SLNG 

0.02726

SLWG 

0.0002162

SLNG 0.028

SLWG 

0.00054

SLNG

1.1E-03

SLWG

2.2E-05

SLNG 

1.3E-05

SLWG 

2.5E-07

Applicator

Applicator –

groundboom – open 

cab

0.0001987 SLNG 

0.0001316 0.00033 1.4E-05 1.5E-07

1. Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/acre) x Area Treated (acres/day) x %Absorption (3.5% dermal and 100% inhalation) / Body 

weight (60 kg in corn assessment and 70 kg in soybean assessment).

2. Combined ADD (mg/kg/day) = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day).

3. Corn assessment: [PHED Unit Exposure (μg/lb ai handled) x % absorption x application rate (lb ai/acre) x 

acres treated/day x 1 mg/1000 μg 70-kg body weight*] x # of days to treat average field x number applications/year x # of farms treated by commercial handler 

365 days/year x 35/70**. Soybean assessment: Commercial Applicator LADD (mg/kg/day) = ADD x [(30 days/yr)/ (365 days/yr)] x (35 yrs/70yrs).

4 Commercial Applicator Cancer Risk = Commercial LADD x Q1* [1.14 x 10-2(mg/kg/day)-1].

Table A4.4. Summary of Occupational Post-application Non-Cancer Exposure Scenarios and Risk for Isoxaflutole.

Soybeans

Exposure 

Scenario 

Assessed

DP #

Application

Rate

(lb ai/A)

DFR1

Transfer 

Coefficient 

(cm2/hr)

Daily Dose2

(mg/kg/day)

MOE3

ST IT

Field/row crop, 

low/medium Scouting D373091 0.094 0.21 100 0.0001 51,000

The information in the table is based on proprietary and non-proprietary data.

1. DFR (μg/cm2) = Application rate (lb ai/A) x (1 - daily dissipation rate)tx CF (4.54E+8 μg/lb) x CF (2.47E-8 A/cm2) x 20% DFR after initial treatment.

2. Daily Dose = [DFR (ug/cm2) x TC (cm2/hr) x 0.001 mg/μg x Dermal Absorption (3.5%) x 8 hrs/day] ÷ Body Weight (60 kg).

3. LOAEL/Daily Dose (LOAEL = 5.0 mg/kg/day); ST = Short-Term, IT = Intermediate-Term.

Table A4.5. Summary of Occupational Post-application Cancer Exposure Scenarios and Risk for Isoxaflutole.

Soybeans

Exposure 

Scenario 

Assessed

DP # DAT1 DFR2

(ug/cm2)

Transfer 

Coefficient3

(cm2/hr)

Daily Dose4

(mg/kg/day) LADD5 Cancer Risk6

Field/row crop, 

low/medium Scouting D373091 1-30 0.21 100 0.000028 1.2E-06 1.31E-08

1. DAT = 30 day residue average.

2. DFR value used is based on HED standard assumption of 20% of the active ingredient available initially and dissipation of 10% per day thereafter. 

3. Transfer coefficients selected in accordance with ExpoSAC Policy 3.1 (August 2000).

4. Daily Dose (mg/kg/day) = DFR (μg/cm2) x 0.001 mg/ug x TC (cm2/hr) x DA (3.5%) x ET (8 hr/day)/70 kg.

5. LADD (mg/kg/day) = DD x [(30 days/yr)/ (365 days/yr)] x (35 yrs/70yrs).

6. Cancer Risk = LADD x Q1* [1.14 x 10-2(mg/kg/day)-1].
Isoxaflutole Registration Review Human-Health Assessment Scoping Document

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Attachment 5: Isoxaflutole International Residue Limit Status Sheet.

Isoxaflutole (123000; 1/11/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

U.S. Canada Mexico2 Codex

40 CFR 180.537:

Plant: isoxaflutole, 5-cyclopropyl4-(2-methylsulfonyl-4-

trifluoromethylbenzoyl) isoxazole 

and its metabolite 1-(2-

methylsulfonyl-4-

trifluoromethylphenyl)-2-cyano-3-

cyclopropyl propan-1,3-dione 

(RPA 202248), calculated as the 

parent compound.

Livestock: None

Plant: (5-cyclopropyl-4-isoxazoly)[2-

(methylsulfonyl)-4-

(trifluoromethyl)phenyl]methanone, including 

the metabolites 1-(2-methylsulfonyl-4-

trifluorometylphenyl)-2-cyano-3-

cyclopropylpropane and 2-metyhlsulfonyl-4-

trifluorometyl benzoic acid, as parent equivalent.

Livestock/Dairy Commodities: (5-cyclopropyl4-isoxazoly)[2-(methylsulfonyl)-4-

(trifluoromethyl)phenyl]methanone, including 

the metabolite 1-(2-methylsulfonyl-4-

trifluoromethylphenyl)-2-cyano-3-

cyclopropylpropane, as parent equivalent.

None

Commodity1 Tolerance (ppm)/Maximum Residue Limit (mg/kg)

U.S. Canada Mexico2 Codex

Corn, field, forage 0.04

Corn, field, grain 0.02 0.02 Field corn

Corn, field, stover 0.02

MRLs with no U.S. equivalent

Eggs 0.01

Liver of cattle 0.5

Liver of poultry 0.3

Meat byproducts of cattle 0.1

Meat byproducts of hogs 0.1

Meat byproducts of horses 0.1

Meat byproducts of poultry 0.1

Meat byproducts of sheep 0.1

Meat of cattle 0.2

Meat of hogs 0.2

Meat of horses 0.2

Meat of poultry 0.2

Meat of sheep 0.2

Milk 0.02

Completed: M. Negussie; 1/11/2010

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.