Fluazifop-P-butyl Human Health Risk Assessment DP No. 0 420423 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 2 1-JUL-20 15 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Fluazifop-P-Butyl. Human-Health Risk Assessment for Sweet Potato Label 

Amendment and Resulting Tolerance Increase. 

PC Code: 122809 

Decision No.: 489431 

Petition No.: 4F8262 

DP Barcodc: D420423 

Registration No.: 100-1001, 100-1070 

Regulatory Action: Label Amendment 

Risk Assessment Type: Single chemical Case No.: NA 

aggregate 

TXR No.: NA CAS No.: 7924 1-46-6 

MRID No.: NA 40 CFR: §180.41 1 

FROM: 

THROUGH: 

TO: 

Ronnie 

WilliamH.Donovan

J. Bever Jr., Toxicolo

, Chemis

g

t 

ist 

LJ~ ~ 1 ~ · 'f}-&v-eA/'TI · 

Alexandra Gavelek, Biologist ~ I - , , '-t,t G CL/ 

Risk Assessment Branch V & VII 

f lealth Effects Division (7509P) 

Michael S. Metzger, Branch Chief ~I nJ). Risk Assessment Branch V & VII ~ Health Effects Division (7509P) 

Banza Djapao, Environmental Protection Specialist 

Fungicide Herbicide Branch 

Registration Division 

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Fl uazi fop-P-butyl Human Health Risk Assessment DP No. D420423 

Table of Contents 

1.0 Executive Sun1n1ary .. ....................... ............. ...................................... .............. ... ....... ......... 4 

2.0 1-IED Recomrnendations .......... .... ... ..... .... ................ ............ .... ....... .... ... ... .................. ......... 6 

2.1 Data Deficiencies ..................................................... .... .... ..................... ..................... ...... 6 

2.2 Tolerance Considerations ............................. .... .... .... .... ....................................... ... .......... 6 

2.2.1 Enforcement Analytical Method ......................................... ..................... .................... 6 

2.2.2 Recommended Tolerances ............................................................................................ 6 

2.2.3 Revisions to Petitioned-For Tolerances ........................................................................ 7 

2.2.4 International H.armonization ..... .... ................. .... .... ................................................. ...... 7 

2.3 Label Recon1mendations .......... .... ......................... .... .... ... ................................... .... ......... 7 

3.0 Introduction .......................................................................... ....... ..................... ... ................. 7 

3. I Chemical Identity ..... .... ............... .... ........ ..... .... .... .... .... ... .... ....... ... .... ............................... 7 

3.2 Physical/Chemical Characteristics ............................................. ... ........... ... .... ... .............. 8 

3.3 Pesticide Use Pattern ....... .... ............................................ ................................................. 8 

3.4 Anticipated Exposure Pathways ....................................................................................... 8 

3.5 Consideration of Environmental Justice .......................................................................... 9 

4.0 Hazard Characterization and Dose-Response Assessment .................................................. 9 

4.1 Summary of Toxicological Effects .... ................. .... .... ..................................................... 9 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) .............................. ......... 1 1 

4.2.1 Completeness of the Toxicology Database .... ........ .... .... ....... ... .... ....... ... .... ................ 12 

4.2.2 Evidence of Neurotoxicity ..... .... .... .... .... ......... ...................... .... .......... .... ... ................. 12 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ............. 12 

4.2.4 Residual Uncertainty in the Exposure Database .... ..................................................... 14 

4.3 Toxicity Endpoint and Point of Departure Selections .................................................... 14 

5.0 Dietary Exposure and Risk Assessment ............................................................................ 18 

5.1 Residues of Concern Summary and Rationale ............................................................... 18 

5.2 Food Residue Profile ........ ........ ........ ................................................................... ....... .... 18 

5.3 Water Residue Profile ... ... .... .... ............ ............ .... ............ ... ....................................... .... 18 

5.4 Dietary Risk Assessment .. ................................ ....................... ... .... ................................ 19 

5.4.1 Description of Residue Data Used in Dietary Assessment.. ............................... ........ 19 

5.4.2 Percent Crop Treated Used in Dietary Assessment.. .................................................. 19 

5.4.3 Acute Dietary Risk Assessment ............................................................................ ..... 19 

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 20 

5.4.5 Cancer Dietary Risk Assessment.. .............................................................................. 20 

5.4.6 Summary Table ........................................................................................................... 20 

6.0 Residential (Non-Occupational) Exposure/Risk Characteri zation .............. .... .............. .... 20 

6.1 Residential Handler Exposure ........................................................................................ 21 

6.2 Residential Post-application Exposure/Risk Estimates ... ... .... ........................ ........... ... .. 23 

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 23 

6.4 Spray Drift .................................................. ................. ....... .... ....... ... .... ....... ................... 24 

6.5 Residential Bystander Post-Application Inhalation Exposure ....................................... 24 

7.0 Aggregate Exposure/Risk Characterization ....................................................................... 25 

7. l Acute Aggregate Risk .................................................................................................... 25 

7.2 Short-Term Aggregate Risk ................................ ................................................... ........ 25 

7.3 Intermediate-Term Aggregate Risk ................................................................................ 26 

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Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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7.4 Chronic Aggregate Risk................................................................................................. 26

8.0 Cumulative Exposure/Risk Characterization..................................................................... 26

9.0 Occupational Exposure/Risk Characterization .................................................................. 26

10.0 References.......................................................................................................................... 27

Appendix A. Toxicology Profile and Executive Summaries....................................................... 28

A.1 Toxicology Data Requirements...................................................................................... 28

A.2 Toxicity Profiles............................................................................................................. 29

Appendix B. Physical/Chemical Properties................................................................................. 37

Appendix C. Review of Human Research ................................................................................... 38
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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1.0 Executive Summary

Fluazifop-P-butyl [(R)-2-(4-((5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoic acid, butyl 

ester] is a selective herbicide registered for use to provide postemergence control of perennial 

and annual grass weeds. Fluazifop-P-butyl is the R enantiomer of fluazifop-butyl [(R,S)-2-(4-

((5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoic acid, butyl ester]. Fluazifop-butyl (PC 

Code 122805) registrations have been cancelled and only fluazifop-P-butyl registrations are 

currently supported. Fluazifop-P-butyl is currently registered for food/feed use on many 

agricultural crops. Fluazifop-P-butyl products are typically applied as postemergence foliar or 

soil applications using ground or aerial equipment.

In the current petition (PP# 4F8262), Syngenta has requested a label amendment to reduce the 

sweet potato preharvest interval (PHI) from 55 to 14 days, and requested an increase in the sweet 

potato root tolerance from 0.05 to 1.5 ppm. 

The toxicology database for fluazifop-P-butyl consists of studies conducted using fluazifop-butyl 

(racemic mixture) and its enriched R-isomer, fluazifop-P-butyl. Comparison studies have shown 

similar toxicities from both compounds. The toxicity database for fluazifop-P-butyl is complete 

and adequate for characterization of potential developmental, reproductive, carcinogenetic, 

mutagenic, immunotoxic, and neurotoxic effects. The liver and kidney are the target organs, and 

the toxicity is expressed as liver toxicity in the presence of peroxisome proliferation and 

exacerbation of age-related kidney toxicity. 

An acute dietary endpoint for the general U.S. population, including infants and children, was 

not identified. An acute dietary endpoint for females 13-49 years of age was selected from a 

developmental toxicity study in rats based on diaphragmatic hernia (NOAEL=50 mg/kg/day). 

The short-term incidental oral endpoint was selected from the developmental toxicity studies in 

rats and is based on maternal body weight gain decrement (NOAEL=100 mg/kg/day). The 

chronic dietary (all populations), intermediate-term dermal and inhalation, and intermediate term 

incidental oral endpoints were selected from the two-generation reproduction study in rats based 

on decreased spleen, testes and epididymal weights in males, and decreased uterine and pituitary 

weights in females (NOAEL = 0.74 mg/kg/day). The short-term dermal for adults and inhalation 

endpoints used in the assessment were selected from the developmental toxicity studies in rats 

based on decreased fetal weights, hydroureter, and delayed ossification (NOAEL = 2 

mg/kg/day). The short-term dermal endpoint for children used in the assessment was selected 

from the developmental toxicity studies in rats based on maternal body weight gain decrement 

(NOAEL=100 mg/kg/day). Because oral NOAELs were selected for dermal and inhalation 

endpoints, dermal absorption factors were used for oral-dermal route-to-route extrapolation, and

inhalation toxicity was assumed to be equivalent to oral toxicity. Fluazifop-P-butyl is classified 

as “not likely to be carcinogenic to humans”, and no mutagenic potential was observed in 

adequate in vivo and in vitro studies with fluazifop-P-butyl.

HED recommends that the required 10X FQPA Safety Factor be reduced to 1X, because no 

increase in offspring sensitivity over parent was seen in the developmental or reproduction 

studies, no evidence of neurotoxicity was observed, and the exposure assessments are unlikely to 

underestimate exposure.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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The fluazifop-P-butyl residue chemistry database supports the present petition, as adequate field 

trial data reflecting the amended use pattern for sweet potato were submitted. Using the 

Organization for Economic Cooperation and Development (OECD) Maximum Residue Limit 

(MRL) calculation procedures with residues reflecting the proposed shorter PHI of 14 days, the 

recommended tolerance level for sweet potato roots is 1.5 ppm. 

Acute and chronic risk assessments were conducted for dietary exposure (food and water),

including all registered crops and the new residue data for sweet potatoes. The acute dietary 

analysis was unrefined (i.e., 100% crop treated and tolerance level residues). The resulting acute 

dietary exposure estimate for females 13-49 years old, the only relevant population subgroup, 

was 14% aPAD. The chronic dietary analyses were partially refined making use of average 

residues from the supervised field trials, percent crop treated estimates and empirical processing 

factors, where available. The resulting chronic exposure estimates were less than HED’s level of 

concern (≤100% chronic PAD) for general U.S. population (17% cPAD) and all population subgroups. The most highly exposed population subgroup was Children 1-2 years old with an 

estimated risk of 64% cPAD. 

Existing residential uses of fluazifop-P-butyl were reassessed to reflect the updates in HED’s 

2012 Residential SOPs1along with policy changes for body weight assumptions. All residential 

handler margins of exposure (MOEs) are greater than the level of concern (LOC) and are not of 

concern. Further, all residential post-application MOEs are greater than the LOC and not of 

concern. An updated occupational assessment is not required for the current label amendment.

An updated short-term aggregate (food, drinking water and residential exposures) risk 

assessment gave risk estimates below HED’s LOC for children and adults. Based on current and 

proposed uses of fluazifop-P-butyl, neither intermediate- nor long-term aggregate exposures are 

expected.

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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf).

This risk assessment relies, in part, on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical (Appendix C). These studies are subject 

to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with 

applicable ethics requirements. 

2.0 HED Recommendations

HED has no objections to the proposed sweet potato label amendment specifying a PHI of 14 

days and the resulting tolerance increase to 1.5 ppm for sweet potato roots.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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2.1 Data Deficiencies

Turf Transferable Residue (TTR): In accordance with 40 CFR 158, turf transferable residue 

(TTR) data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational 

areas) or residential turf uses that could result in post-application exposure to turf. TTR data are 

required for fluazifop-P-butyl based on HED’s guidance on requiring/waiving TTR/DFR data2, 

as described below.

Since the estimated residential turf postapplication exposure for residential turf using default 

TTR values for fluazifop-P-butyl is not minimal in comparison to the level of concern (i.e., the 

calculated MOE is not greater than 10 times higher than the level of concern, MOE < 1000 

compared to the LOC of 100), future refinements of this postapplication exposure for fluazifopP-butyl may be necessary due to increased use of fluazifop-P-butyl or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40 CFR TTR data to facilitate any necessary 

exposure assessment refinements and to further EPA’s general understanding of the availability 

of turf transferable pesticide residues.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methodology (High Performance Liquid Chromatography/Ultra-Violet 

Spectrometry (HPLC/UV)) is available to enforce the tolerance expression. The method is 

available in Pesticide Analytical Methods (PAM), Volume II: Method I for animal tissues and 

milk and Method II for crops. The stated detection limits are 0.02-0.05 ppm for crops, 0.01 ppm 

for milk, and 0.02 ppm for animal tissues. Improved enforcement methods based on liquid 

chromatography and tandem mass spectroscopy, LC/MS/MS, are available as Method 

GRM044.01A and Method GRM044.02A. Both of these methods have been validated at 0.01 

ppm on a wide variety of crop matrices. 

2.2.2 Recommended Tolerances

Tolerances are currently established under 40 CFR §180.411 for residues of fluazifop-P-butyl

in/on many commodities. HED recommends that the residue definition for the fluazifop-Pbutyl tolerance expression be revised to read as follows:

“Tolerances are established for residues of the herbicide fluazifop-P-butyl, butyl (2R)-2-

[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoate, including its metabolites 

and degradates, in or on the commodities listed below. Compliance with the tolerance 

levels specified below is to be determined by measuring only those fluazifop-P-butyl 

residues convertible to fluazifop, 2-[4-[[5-(trifluoromethyl)-2-

pyridinyl]oxy]phenoxy]propanoic acid, expressed as fluazifop, in or on the commodity”.

 

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

Studies. 10/23/2014, Exposure Science Advisory Council 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Table 2.2.3. Tolerance Summary for Fluazifop-P-Butyl.

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Sweet potato, roots 1.5 1.5

2.2.3 Revisions to Petitioned-For Tolerances

None.

2.2.4 International Harmonization

Codex has not established fluazifop-P-butyl Maximum Residue Limits (MRLs) in/on any 

commodity. Most of the Canadian MRLs are harmonized with the U.S. tolerances. However, 

the Canadian MRL for sweet potato is 0.5 ppm, while the recommended U.S. tolerance is 1.5 

ppm. Harmonization of the U.S. tolerance with the Canadian MRL is not possible since the 

results of field trials reflecting a 14-day PHI show that residue levels in sweet potato roots may 

exceed 0.5 ppm.

2.3 Label Recommendations

None.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Fluazifop-P-butyl Nomenclature.

Compound

N

F3C

O

O

H

CH3

O

O

C4H9(n)

Empirical Formula C19H20F3NO4

Common name Fluazifop-P-butyl

Company experimental name Not available.

IUPAC name Butyl (2R)-2-(4-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoate

CAS name (R)- 2-(4-((5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoic acid, butyl ester

CAS registry number 79241-46-6

End-use product (EP) Fusilade® DX Herbicide (2 lb ai/gal EC; EPA Reg. No. 100-1070)

Chemical Class Phenoxy
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Table 3.1. Fluazifop-P-butyl Nomenclature.

Compound

N

F3C

O

O

H

O

OH

CH3

Common name Fluazifop-P (free acid)

Company experimental name R151672

Chemical name (R)-2-(4-[5-(trifluoromethyl-2-pyridinyl)oxy]phenoxy)propionic acid

3.2 Physical/Chemical Characteristics

The physical/chemical properties of fluazifop-P-butyl are summarized in Appendix B. The 

compound is not particularly volatile (vapor pressure = 3 x 10-8kPa), and the log KOW (4.5) 

suggests a potential to partition into fatty tissues or bioaccumulate. 

3.3 Pesticide Use Pattern

The label directions are clear and complete. Table 3.3 provides a summary of the proposed use 

directions on sweet potato, which include a reduced PHI of 14 days as compared to the 55 day 

PHI on the existing label. The submitted field trials reflect the maximum application rates and 

follow the proposed label directions. 

Table 3.3. Summary of Directions for Use of Fluazifop-P-Butyl.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

RTI 

(days)

PHI 

(days)

Use Directions and 

Limitations

Sweet Potato

Foliar broadcast Fusilade DX

[100-1070] 0.1875 4 0.75 14 14 Use crop oil concentrate or non-ionic surfactant

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the label 

amendment request to reduce the PHI for use of fluazifop-P-butyl on sweet potatoes. Humans 

may be exposed to fluazifop-P-butyl residues in food and drinking water, since fluazifop-P-butyl

may be applied directly to growing crops and application may result in fluazifop-P-butyl

reaching surface and ground water sources of drinking water. There are residential uses of 

fluazifop-P-butyl, so an assessment of exposure in residential settings is provided. In an 

occupational setting, applicators may be exposed while handling the pesticide prior to 

application, as well as during application. There is a potential for post-application exposure for 

workers re-entering treated fields. 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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This risk assessment considers all of the aforementioned exposure pathways based on the 

amended and existing uses of fluazifop-P-butyl, 

3.5 Consideration of 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://epa.gov/compliance/ej/resources/policy/exec_order_12898.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 

National Health and Nutrition Survey/What We Eat in America (NHANES/WWEIA) 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 based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas postapplication 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.

4.0 Hazard Characterization and Dose-Response Assessment

The 2005 risk assessment contained a thorough description of the toxicology profile for 

fluazifop-P-butyl (Locke, 2005, D316891). The database is adequate for FQPA assessment, 

endpoint selection, and dose-response evaluation for fluazifop-P-butyl and the fluazifop mixed 

isomers. The acute neurotoxicity, subchronic neurotoxicity, and immunotoxicity studies have 

been screened, and effects observed in these studies are not expected to result in risk concerns. 

Consequently, the conclusions for the hazard characterization from the 2005 risk assessment are 

unchanged. A full update of the hazard characterization will be conducted in support of petition 

for new crop uses.

4.1 Summary of Toxicological Effects

Fluazifop-butyl is an herbicide with mixed isomeric [RS] content, while fluazifop-P-butyl is the 

purified [R] enantiomer and is the only herbicide currently registered. Fluazifop-P-butyl acts in 

plants by inhibiting acetyl CoA carboxylase, a key enzyme in plant fatty acid synthesis and 

required for maintaining membranes in functioning condition. Peroxisome proliferation was 

shown in rat and mouse, and to a lesser extent in the hamster, in vivo, and human liver cells, in 

vitro.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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The toxicological database on fluazifop-butyl is complete with sufficient data available showing 

equivalence of fluazifop-butyl (FB, PC code 122805) with fluazifop-P-butyl (FPB, PC code 

122809) in animal toxicity. The toxicity database is adequate to carry out FQPA assessment, 

endpoint selection, and dose-response evaluation for both chemicals.

Metabolism studies have been conducted in the rat with fluazifop-butyl, and absorption, 

excretion, and confirmatory metabolism studies in the dog with fluazifop-butyl, and hamster with 

fluazifop-P-butyl. Comparative metabolism studies in the rat show that both fluazifop-P-butyl 

and fluazifop-butyl mixed isomers are rapidly hydrolyzed to fluazifop acid and the [S] 

enantiomer is rapidly converted to the [R] enantiomer in the blood, yielding similar toxicities

in vivo. A 50:50 mixture of the two isomers quickly converts to 97% R-isomer in vivo. 

Oral dog and female rat studies show similar results, while male rats show greater toxicity. 

Fluazifop-butyl is rapidly absorbed through the gut after oral dosing, and the ester linkage is 

hydrolyzed to produce the fluazifop acid in the blood. No parent fluazifop-ester was detected in 

plasma at any time. Male rats show similar fluazifop acid excretion to the female, but excretion 

is slower, because fluazifop is excreted in the bile and results in a higher percentage in the feces. 

The greater toxicity in male rats may be due to the longer retention time.

In a metabolism study (MRID 00131464), fluazifop-butyl (99.6% a.i.) was administered to 3 

male humans in a single dose in corn oil on a sugar cube at a dose level of 0.07 mg/kg. The 

results from the study were consistent with the studies in rats and dogs. That fluazifop-butyl is 

rapidly absorbed, hydrolyzed to the free acid and excreted mostly in the urine as the free acid, 

with minor amounts of conjugates of the free acid (conjugates unidentified in humans). The onehalf life in the men studied was closer to that found in female rats, which lacked the delayed 

excretion characteristic of male rats, possibly being due to biliary recycling in male rats. If the 

toxicity of fluazifop-butyl is related to delayed excretion time seen in male rats, then the rapid 

excretion in men in the current study may suggest that the toxicity in men is more closely related 

to the dog and female rats where the excretion time is also short. The ethics of this human study 

was cleared in the memo “Ethics Review of Fluazifop-Butyl Absorption, Distribution and 

Metabolism Study” (Sherman, 2010).

The liver and kidney are its target organs, expressed for the most part as liver toxicity in the 

presence of peroxisome proliferation and exacerbation of age-related kidney toxicity. These data 

are reasonably consistent among the rat with fluazifop-butyl and fluazifop-P-butyl, dog with 

fluazifop-butyl, and hamster with fluazifop-P-butyl. Fluazifop-P-butyl shows similar toxicity by 

both the inhalation and oral routes.

Although the liver and kidney were the organs most consistently affected, other findings were 

used as endpoints for selection of the points of departure. A rat developmental study exhibiting 

diaphragmatic hernia effects was used as the basis to select the acute dietary endpoint for 

females 13-49 years of age, while neurotoxic effects were used for an endpoint for the general 

U.S. population, including infants and children. The short-term incidental oral and children’s 

dermal endpoints were selected based upon a maternal body weight gain decrement exhibited in 

the developmental toxicity studies performed on rats. The chronic dietary (all populations), 

intermediate-term dermal and inhalation, as well as the intermediate-term incidental oral 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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endpoints, were selected from the 2-generation reproduction study in rats. This study was 

significant in exhibiting decreased testes and epididymal weights in males, along with decreased 

uterine and pituitary weights in females. In regard to the short-term dermal endpoint for adults 

and inhalation endpoints used in this assessment, the developmental toxicity studies performed 

on rats were used as the basis for endpoint selection. These studies were notable in exhibiting 

decreased fetal weights, as well as hydroureter and delayed ossification effects. An additional 

endpoint was chosen that was specific for short-term dermal exposure to children, as a 

developmental effect is generally protective of pregnant women and fetuses. In this case, the 

maternal toxicity (body weight gain decrement) was chosen to be protective of children. In 

summarizing the available toxicity data on fluazifop-P-butyl, the established toxicity endpoints 

for risk assessment are presented in Section 4.3, and the toxicity profile tables are provided in 

Appendix A.

Indications of possible neurotoxicity were observed in the acute neurotoxicity study, including 

clinical signs indicative of toxicity (reduced activity, decreased rearing, hunched posture and/or 

piloerection), decreased body temperature, and decreased motor activity (total distance and 

number of rearings). No signs of neurotoxicity were observed in the subchronic neurotoxicity 

test at doses up to 70 mg/kg/day in males and 328 mg/kg/day in females. There was no observed

immunotoxicity resulting from fluazifop-P-butyl exposure in the submitted study. There was no 

carcinogenicity observed in acceptable studies in the rat with fluazifop-butyl or in the hamster 

for fluazifop-P-butyl. The hamster was selected for cancer study, because liver peroxisome 

proliferation more closely resembled what was found for human liver cells. There was no 

mutagenicity observed for fluazifop-butyl or fluazifop-P-butyl. 

In a dermal absorption and pharmacokinetic study in humans (MRID 46082918, ethics of study 

cleared - see Lowe, 2006), most of the applied dose appeared to be in the stratum corneum and 

easily removed (the unrecovered test material was speculated to be in the outer layers of the 

skin). Peak plasma levels were shown to occur 24 to 31 hours after application in these men. 

The one half-life for excretion was about 18 hours. In the 2005 risk assessment, HED (Locke, 

2005, D316891) modified the study author’s percentage absorption estimates by scaling the 

amount of recovered material to 100%, yielding absorption factors of 9% and 2% at the 2 mg 

dose and 200 mg dose, respectively.

Fluazifop-P-butyl has low volatility, is not an eye or skin irritant in acute or 21-day dermal 

studies, and is not a skin sensitizer. Only low acute toxicity was observed: toxicity category IV 

for eye and dermal irritation and toxicity category III for acute oral, dermal, and inhalation 

toxicity.

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

No increased offspring sensitivity over parent was seen in the rabbit pre-natal developmental 

studies or the rat post-natal reproduction study, and no evidence of neurotoxicity was observed. 

Although malformed fetuses were seen at high dose levels in the absence of maternal toxicity in 

the rat developmental toxicity studies, the definitive developmental endpoints in five 

developmental studies were selected based on delayed ossification and fetal weight decrement at 

much lower doses (100-fold lower). 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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There is an adequate toxicity database for fluazifop-P-butyl and exposure data are complete. 

There are no residual uncertainties pertaining to pre- and post-natal toxicity, and no 

developmental neurotoxicity or immunotoxicity was observed. The dietary (food and drinking 

water) exposure assessments are conservative. The dietary and residential assessments are based 

on reliable data and will not underestimate exposure/risk. Based on these data and conclusions, 

the FQPA Safety Factor can be reduced to 1X. 

Although EPA has required additional data on transferable residues from treated turf for 

fluazifop-P-butyl, EPA is confident that it has not underestimated turf exposure, due to the 

conservativeness of the default turf transfer value and conservative assumptions in the short-term 

turf assessment procedures (e.g., assuming residues do not degrade over the thirty day 

assessment period and assuming high-end activities on turf for every day of the assessment 

period). The additional data on transferable turf residues have been required in case refinement 

of exposure assessments is needed in the future and to further EPA’s general understanding of 

the availability of turf transferable pesticide residues.

4.2.1 Completeness of the Toxicology Database

The toxicology database for fluazifop-butyl and fluazifop-P-butyl is currently considered 

complete. The selected points of departure are protective for any immunotoxic or neurotoxic 

effect. Acceptable developmental toxicity studies in rats and rabbits on fluazifop-butyl and 

fluazifop-P-butyl are available, in addition to an acceptable 2-generation reproduction study in 

rats. Studies on fluazifop-butyl may be used to support fluazifop-P-butyl, due to equivalency in 

toxicity. A comprehensive overview of the fluazifop-butyl/fluazifop-P-butyl toxicology database 

is provided in Appendix A.

4.2.2 Evidence of Neurotoxicity

The assessment team concluded that there was not a concern for neurotoxicity resulting from 

exposure to fluazifop-P-butyl at relevant exposure levels. There was no evidence of clinical 

signs indicative of neurotoxicity or neuropathology in the available studies (excluding the 500 

mg/kg gavage dose in the acute neurotoxicity study). Marginal increases in brain weights at 

termination were seen in a subchronic toxicity study in rats and a carcinogenicity study in 

hamsters, but only at high doses. A developmental neurotoxicity study is not required at this 

time.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

While there was quantitative evidence of increased susceptibility in the fetuses of rats exposed 

in utero to fluazifop-butyl and fluazifop-P-butyl, the degree of concern is low based on the 

following considerations: the endpoint of concern (delayed ossifications) is considered to be a 

developmental delay as opposed to a malformation or variation, which is considered to be more 

serious in nature; there were considerable variations in the incidences among the five studies; the 

NOAELs/LOAELs for this effect were well-defined and consistent across these studies; and a 

developmental endpoint of concern (diaphragmatic hernia) is used for assessing acute dietary 

risk. Also, in a two-generation reproduction toxicity study in rats, there was no evidence 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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(quantitative or qualitative) of increased susceptibility following in utero exposures to rabbits or 

following pre-and/or postnatal toxicity. Therefore, there is no residual uncertainty for pre and/or 

postnatal toxicity.

As there is limited indication of developmental neurotoxicity resulting from exposure to 

fluazifop-P-butyl with the current data sets, there is no need for a developmental neurotoxicity

study. There were no developmental or central nervous system malformations seen in any of the 

developmental toxicity studies with rats or rabbits and no evidence of neurotoxicity or 

neuropathology in adult animals in the available studies. The toxicological significance of the 

marginal increases in brain weights at high doses is unknown in the absence of corroborative 

histopathological lesions. The assessment team concluded that there is not a concern for 

developmental neurotoxicity resulting from exposure to fluazifop-butyl or fluazifop-P-butyl. 

The database included 7 developmental toxicity studies: 2 with fluazifop-butyl in SpragueDawley rats, 3 with fluazifop-P-butyl in Wistar rats, 1 with fluazifop-butyl in New Zealand 

rabbits, and 1 with fluazifop-P-butyl in New Zealand rabbits. The toxicology database is 

adequate for hazard characterization and endpoint selection. Therefore, no database uncertainty 

factors are needed for any database deficiencies. These studies are summarized below:

The NOAEL/LOAEL in the five rat developmental toxicity studies was determined by a weight 

of evidence criteria mainly around consistency of delayed ossification, delayed development of 

the urinary tract, and diaphragmatic hernias. Although, delayed ossification was seen in some 

studies at lower doses, they were inconsistent (i.e., low incidence of delayed ossification in 

controls compared to historical controls, large variation in historical controls, the delayed 

ossification was not clearly dose-related, and litter incidence was not statistically significant). 

The LOAEL is 5.0 mg/kg/day based on decreased fetal weight and increased incidence of 

hydroureter in fetuses and litters, and delayed ossification in a 160 litter/group developmental 

toxicity study (MRID 00088858). This LOAEL is also supported by a dose-related increased 

fetal incidence in partially ossified sternebrae and sternebrae bipartite, 5th (MRIDs 46082913

and 46082903), and statistically significant increased incidence of fetuses and litters with 

interparietals, occipitals, and parietals partially ossified, calcaneum not ossified, and increased 

manus and pes scores at 5.0 mg/kg/day (MRIDs 46082903 and 46158401). The NOAEL of 1.0 

mg/kg/day in the 160 litter per group study was not selected, and a NOAEL of 2.0 mg/kg/day 

from the Wistar rat studies was selected. Since apparent effects noted at 0.05 and 1.0 mg/kg/day 

were either not dose-related, concurrent controls were low, the effects were lower than the 

historical control range, or were not statistically significant in litters, and 2 developmental 

studies that included a 2 mg/kg/day dose group failed to elicit a dose-dependent response, a 

NOAEL of 2.0 mg/kg/day was selected.

The overall rat studies showed a NOAEL/LOAEL of 2.0/5.0 mg/kg/day. The NOAEL/ LOAEL 

was chosen from among MRIDs 0008858, 46082903, 46082913, and 46518401. For a single 

dose effect, the NOAEL/LOAELs are 50/200 mg/kg/day based on the diaphragmatic hernia 

malformations.
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The maternal toxicity NOAEL/LOAEL of 100/300 mg/kg/day was based on a combination of 

factors. There was a clear effect on maternal body weight gain decrement at 300 mg/kg/day in 

the Wistar rat studies and a clear NOAEL at 100 mg/kg/day in the Wistar rat studies. Although, 

the maternal weight decrement in the Sprague Dawley rat was shown to be due to gravid uterine 

weight decrement, it was not completely clear that maternal toxicity was not expressed at 200 

mg/kg/day. Therefore, the maternal NOAEL was chosen among the three Wistar rat 

developmental toxicity studies to remove this ambiguity in maternal toxicity. 

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary and non-dietary 

exposure estimates were based on several conservative assumptions, HED is confident that the 

exposure estimates are not underestimated.

Although EPA has required additional data on transferable residues from treated turf for 

fluazifop-P-butyl, EPA is confident that it has not underestimated turf exposure, due to the 

conservativeness of the default turf transfer value and conservative assumptions in the short-term 

turf assessment procedures (e.g., assuming residues do not degrade over the thirty day 

assessment period and assuming high-end activities on turf for every day of the assessment 

period). The additional data on transferable turf residues have been required in case refinement 

of exposure assessments is needed in the future and to further EPA’s general understanding of 

the availability of turf transferable pesticide residues.

The acute and chronic dietary assessments are conservative evaluations. The acute assessment 

utilized tolerance level residues for all crops. In addition, default processing factors were 

assumed for all commodities. One hundred percent crop treated was assumed for all 

commodities. A partially refined analysis was performed for the chronic assessment, using 

percent crop treated, average field trial residue levels and empirical or default processing factors, 

as appropriate. Both the acute and chronic food plus water analyses were performed with the 

DEEM-FCIDTM model, which assumes that all drinking water will contain fluazifop-P-butyl at 

the highest estimated drinking water concentration (EDWC) levels modeled by EFED for ground 

water or surface water. For these reasons, it can be concluded that the dietary analysis does not 

underestimate risk from exposure to fluazifop-P-butyl.

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment and/or cancer classification. 

The current toxicity endpoints and points of departure for various exposure scenarios are 

presented in Tables 4.3.1 and 4.3.2 below. 
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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Fluazifop-Butyl 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, 

Including 

Infants and 

Children)

- - - An appropriate endpoint attributable to a 

single dose was not identified in the 

available studies including the 

developmental toxicity studies.

Acute Dietary 

(Females 13-

49 years of 

age)

NOAEL= 

50 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Acute RfD = 

aPAD = 0.50

mg/kg 

00008857, 92067047, 00088858, 

92067048, 92967020, Rat developmental

Developmental LOAEL = 200 

mg/kg/day based on diaphragmatic 

hernia

Chronic 

Dietary (All 

Populations)

NOAEL= 

0.74 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Chronic RfD 

= cPAD = 

0.0074

mg/kg/day 

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Incidental 

Oral ShortTerm (1-30 

days)

NOAEL= 

100 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

46158401, Rat developmental

LOAEL = 300 mg/kg/day based on 

maternal body weight gain decrement 

during GD 7-16

Incidental 

Oral 

IntermediateTerm (1-6 

months)

NOAEL= 

0.74 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Dermal ShortTerm (1-30 

days; 

children)

NOAEL= 

100 

mg/kg/day

DAF=9%

(low 

exposure) 

or 2% 

(highexposure)

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

46158401, Rat developmental

LOAEL = 300 mg/kg/day based on 

maternal body weight gain decrement 

during GD 7-16
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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Fluazifop-Butyl 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

Dermal ShortTerm (1-30 

days; adults)

NOAEL= 

2.0 

mg/kg/day

DAF=9%

(low 

exposure) 

or 2% 

(highexposure)

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

00088858, 92067048, 92967020, Rat 

developmental

Developmental LOAEL = 5.0 mg/kg/day 

based on fetal weight decrement, 

hydroureter, and delayed ossification

Dermal 

Intermediateand LongTerm (1-6 

months and 

>6 months)

NOAEL= 

0.74 

mg/kg/day

DAF=9%

(low 

exposure) 

or 2% 

(highexposure)

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Inhalation 

Short-Term 

(1-30 days)

NOAEL= 

2.0 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

00088858, 92067048, 92967020, Rat 

developmental

Developmental LOAEL = 5.0 mg/kg/day 

based on fetal weight decrement, 

hydroureter, and delayed ossification

Inhalation 

Intermediateand LongTerm (1-6 

months and 

>6 months)

NOAEL= 

0.74 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=1x

Residential 

LOC for 

MOE = 100

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Cancer (oral, 

dermal, 

inhalation)

Not likely to be carcinogenic to humans

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. 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). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c 

= chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. 

DAF = dermal absorption factor.
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Table 4.3.2. Summary of Toxicological Doses and Endpoints for Fluazifop-Butyl 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

Dermal ShortTerm (1-30 

days)

NOAEL= 

2.0 

mg/kg/day

DAF=9%

(low 

exposure) 

or 2% 

(highexposure)

UFA=10x

UFH=10x

Occupational 

LOC for MOE = 

100

00088858, 92067048, 92967020, Rat 

developmental

Developmental LOAEL = 5.0 mg/kg/day 

based on fetal weight decrement, 

hydroureter, and delayed ossification

Dermal 

Intermediateand LongTerm (1-6 

months and >6 

months)

NOAEL= 

0.74 

mg/kg/day

DAF=9%

(low 

exposure) 

or 2% 

(highexposure)

UFA=10x

UFH=10x

Occupational 

LOC for MOE = 

100

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Inhalation 

Short-Term 

(1-30 days)

NOAEL= 

2.0 

mg/kg/day

UFA=10x

UFH=10x

Occupational 

LOC for MOE = 

100

00088858, 92067048, 92967020, Rat 

developmental

Developmental LOAEL = 5.0 mg/kg/day 

based on fetal weight decrement, 

hydroureter, and delayed ossification

Inhalation 

Intermediateand LongTerm (1-6 

months and >6 

months)

NOAEL= 

0.74 

mg/kg/day

UFA=10x

UFH=10x

Occupational 

LOC for MOE = 

100

00088859, 92067050, Rat reproduction

LOAEL = 5.8 mg/kg/day based on 

decreased testes and epididymal weights

Cancer (oral, 

dermal, 

inhalation)

Not likely to be carcinogenic to humans

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. 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). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
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5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized 

in Table 5.1. The parent and fluazifop acid (free and conjugated) were identified as the residues 

of concern for the tolerance expression for plant and livestock commodities. The metabolites 5-

trifluoromethyl-2-pyridone, and 2-(4-hydroxyphenoxy)propionic acid (free and conjugated) were 

also identified as residues of concern to include in the dietary risk assessment for plants. These

metabolites were assumed to have equal toxicity to the parent compound. Parent and fluazifop 

acid were the major degradates in the environmental fate studies and were included in the 

drinking water assessment. Further information on the metabolism and degradation may be 

found in the Metabolism Assessment Review Committee memo for fluazifop-P-butyl (TXR No. 

0052680, S. Kinard et al., 17-MAR-2004).

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Tolerance 

Expression

Residues included in Risk 

Assessment

Plants Parent and fluazifop acid (free 

and conjugated)

Parent and fluazifop acid (free and 

conjugated), 5-trifluoromethyl-2-

pyridone, and 2-(4-

hydroxyphenoxy)propionic acid 

(free and conjugated)

Livestock Parent and fluazifop acid (free 

and conjugated)

Parent and fluazifop acid (free and 

conjugated)

Drinking Water NA Parent and fluazifop acid

5.2 Food Residue Profile

Crop field trial studies are available to support the label amendment request for sweet potato. 

Thus, eight sweet potato field trials were conducted with the proper geographical distribution in 

the United States following the label amendment use pattern. Residues ranged from 0.11 – 0.85 

ppm, with half of the trials above 0.5 ppm, the current Canadian MRL for sweet potato. 

Analysis of this residue data set using the OECD MRL calculation procedures results in a 

recommended level of 1.5 ppm. Samples were stored frozen for a maximum period of 794 days. 

In a concurrent storage stability study, fluazifop-P-butyl residues were demonstrated to be stable 

in frozen sweet potato samples for at least 922 days. There are no processed commodities or 

livestock feedstuffs associated with sweet potatoes. No rotational crop issues have been 

identified for fluazifop-P-butyl. 

5.3 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) (W. Shaughnessy, D371093, 05/25/2010). 

Estimated drinking water concentrations (EDWCs) in ground water were modeled using Tier I 

SCIGROW (version 2.3) and surface water EDWCs were modeled using Tier II PRZM 

(Pesticide Root Zone Model) and EXAMS (Exposure Analysis Modeling System). The highest 
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EDWCs from the ground and surface water modeling were used in the dietary assessment and 

are summarized in Table 5.3.

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations 

for Fluazifop-P-Butyl.

Scenario Surface Water Conc., ppb a Ground Water Conc., ppb b

Acute 33.4 1.56

Chronic 6.6 1.56

a From the Tier II PRZM-EXAMS - Index Reservoir model. Acute EDWC based on banana use pattern; chronic 

EDWC based on grape use pattern. 

b From the SCI-GROW model.

W. J. Shaughnessy, D371093, 05/25/2010.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The unrefined acute dietary assessment was based on 100% crop treated assumptions and 

tolerance-level residues, adjusted as appropriate using factors from the metabolism studies, to 

account for residues of concern not measured by the analytical method. Water residues were 

also included using point estimates.

The partially refined chronic dietary exposure analysis was based on mean residue levels from 

crop field trials with a ratio adjustment for additional metabolites of concern, average percent 

crop treated estimates, and experimentally determined processing factors (where available; 

otherwise default processing factors were used). 

5.4.2 Percent Crop Treated Used in Dietary Assessment

For the acute dietary analysis, 100% crop treated was assumed for all crops.

The following average percent crop treated estimates (Memo, J. Alsadek, 27-MAR-2015) were 

used in the chronic dietary risk assessments for the following crops that are currently registered 

for fluazifop-P-butyl: apricots, 2.5%; asparagus, 2.5%; carrots, 15%; cherries, 1%; cotton, 1%; 

dry beans/peas. 1%; garlic, 10%; grapefruit, 15%; grapes, 2.5%; nectarines, 1%; onions, 10%; 

oranges, 2.5%; peaches, 2.5%; peanuts, 1%; pecans, 1%; peppers, 2.5%; plums, 2.5%; potatoes, 

1%, prunes, 2.5%; soybeans, 2.5%; and sugar beets, 1%. 100% crop treated was assumed for 

sweet potatoes and all other registered crops not listed above. 

5.4.3 Acute Dietary Risk Assessment

The food plus drinking water results of the acute dietary exposure and risk analysis at the 95th

percentile of exposure are reported in Table 5.4.6, below. The unrefined acute dietary risk 

estimate is below the Agency’s level of concern (<100% aPAD) for the only relevant population 

subgroup, females 13-49 years of age (14% aPAD), at the 95th exposure percentile. 
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5.4.4 Chronic Dietary Risk Assessment

The food plus drinking water results of the chronic dietary exposure and risk analysis are 

reported in Table 5.4.6, below. The analysis indicates that for all supported commodities and 

proposed uses, the chronic dietary risk estimates are below the Agency’s level of concern 

(<100% cPAD) for the U.S. population (17% cPAD) and all population subgroups. The most 

highly exposed population subgroup in the chronic dietary exposure analysis is Children 1-2 

years of age (64% cPAD). 

5.4.5 Cancer Dietary Risk Assessment

As fluazifop-P-butyl has been classified as “Not likely to be carcinogenic to humans”, a cancer 

dietary risk assessment is not required.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for FluazifopP-Butyl.

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

NA NA

0.001244 17

NA NA

All Infants (<1 year old) 0.001577 21

Children 1-2 years old* 0.004756 64

Children 3-5 years old 0.003705 50

Children 6-12 years old 0.001819 25

Youth 13-19 years old 0.001104 15

Adults 20-49 years old 0.000897 12

Adults 50-99 years old 0.000916 12

Females 13-49 years old* 0.067665 14 0.000893 12

*The subpopulations with the highest risk estimates.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs3

along with policy changes for body weight assumptions. The revision of residential exposures 

will impact the human health aggregate risk assessment for fluazifop-P-butyl.

Registered non-agricultural use sites of fluazifop-P-butyl include: non-agricultural outdoor 

buildings, building foundations, curbs, driveways, fencerows, non-agricultural areas (wildlife 

refuge), non-crop areas, ornamentals (lawns, flowering shrubs, flowering plants, gardens, ground 

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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covers, plants, trees, turf, and woody shrubs), patios, pathways, rights-of-way, sidewalks, and 

storage yards. 

6.1 Residential Handler Exposure

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

The combined (dermal and inhalation) residential handler exposure estimates ranged from 230 to 

530; a 9% dermal absorption factor was used to assess dermal residential handler exposures 

because these are considered low exposure activities.
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Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Fluazifop-P-butyl.

Exposure Scenario Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount Handled 

Daily2

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 MOE7

Mixer/Loader/Applicator

Handwand 100 63 0.018 0.01 lb ai/gallon 5 gallons 0.0041 490 0.000013 150,000 490

Hose end sprayer 100 58 0.0014 0.01 lb ai/gallon 11 gallons 0.0083 240 0.0000022 900,000 240

Hose end sprayer 100 13.4 0.022 0.9 lb ai/acre 0.5 acres 0.0079 250 0.00014 14,000 250

Backpack 100 130 0.14 0.01 lb ai/gallon 5 gallons 0.0085 240 0.0001 20,000 230

Sprinkler Can 100 58 0.0014 0.01 lb ai/gallon 5 gallons 0.0038 530 0.000001 2,000,000 530

RTU hose end sprayer 100 6.26 0.034 0.9 lb ai/acre 0.5 acres 0.0037 540 0.0002 9,000 510

RTU hose end sprayer 100 6.26 0.034 0.04 lb ai/gallon 11 gallons 0.0036 560 0.0002 9,200 530

1 Based on registered labels.

2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) × Dermal Absorption Factor 

(%) ÷ Body Weight (kg).

4 Dermal MOE = Dermal NOAEL (2 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ Body Weight (kg).

6 Inhalation MOE = Inhalation NOAEL (2 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

7 Total MOE = NOAEL (2 mg/kg/day) ÷ (Dermal Dose + Inhalation Dose).
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6.2 Residential Post-application Exposure/Risk Estimates

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with fluazifop-P-butyl. 

Consistent with the previous assessment (D316891, D. Locke et al., 29-AUG-2005), two 

separate dermal absorption values are used: 9% is used for assessing dermal exposures while 

golfing or mowing a lawn, since these are representative of low exposure activities, whereas 2% 

is used for assessing dermal exposures from high contact lawn activities, since these are 

representative of high exposure activities. 

Chemical-specific dislodgeable foliar residue (DFR) data are available and were used for the 

residential postapplication exposure assessment for gardens. Since TTR data are not available 

for fluazifop-P-butyl, default TTR values were used for the residential postapplication exposure 

assessment for turf. Given the conservatisms associated with default TTR values and the 

potential compounding nature of conservatisms in the turf assessment, EPA is able to rely upon 

the calculated exposure estimates with confidence that exposure is not being underestimated. All 

residential post-application MOEs are greater than the LOC and are therefore not of concern

(Table 6.2.1). 

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates

Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for FluazifopP-butyl.

Lifestage

Post-application Exposure 

Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3 Combined 

MOE

Use Site Route of 

Exposure

Adult

Turf – High 

Contact

Dermal

0.9 lb ai/acre

0.0078 260 NA

Child (1 to < 2 years)

Dermal 0.0134 7,500 3,700

HtM 0.0137 7,300

OtM 0.00042 240,000 NA

Adult Mowing Dermal 0.9 lb ai/acre 0.00072 2,800 NA

Youth (11 – 16 years) Dermal 0.00071 140,000 NA

Adult

Golfing

Dermal

0.4 lb ai/acre

0.0012 1,600 NA

Youth (11 – 16 years) Dermal 0.0012 81,000 NA

Child (6 to <11 years) Dermal 0.0014 69,000 NA

Adult

Garden

Dermal 

0.4 lb ai/acre

0.0084 240 NA

Child (6 to <11 years) Dermal 0.005 20,000 NA

1 Based on registered labels.

2 Dose (mg/kg/day) equations provided in 2012 Residential SOPs. 

3 MOE = POD (2 mg/kg/day for adults, 100 mg/kg/day for children) ÷ Dose (mg/kg/day).

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3.1 reflects the residential risk estimates via dermal, inhalation, and oral routes that 

should be considered for use in the aggregate assessment for fluazifop-P-butyl. For adults, no 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

Page 24 of 38

incidental oral exposure is expected; for children, incidental oral exposure is possible from handto-mouth or object-to-mouth exposure from turf activities. 

 

Table 6.3.1. Recommendations for the Residential Exposures for the Fluazifop-P-Butyl Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation Oral Dermal Inhalation Oral

Adult Handler 0.0085 0.0001 N/A 240 20,000 N/A

Child Turf 0.0134 N/A 0.0137 7,500 N/A 7,300

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. 

2 MOE = the MOEs associated with the highest residential doses. 

6.4 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for fluazifop-P-butyl. The agency has been working with the Spray Drift 

Task Force (a task force composed of various registrants which was developed as a result of a 

Data Call-In issued by EPA), 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). 4 The agency has also developed a policy 

on how to appropriately consider spray drift as a potential source of exposure in risk assessments 

for pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide 

during the Registration Review process which ensures that all uses for that pesticide will be 

considered concurrently. The approach is outlined in the revised (2012) Standard Operating 

Procedures For Residential Risk Assessment (SOPs) - Residential Exposure Assessment 

Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This document

outlines the quantification of indirect non-occupational exposure to drift. 

6.5 Residential Bystander Post-Application Inhalation Exposure

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

individuals nearby pesticide applications. 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, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux 

studies, route-specific inhalation toxicological studies) or further analysis is required for

fluazifop-P-butyl.

 

4 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute Aggregate Risk

Acute aggregate risks are identical to the acute dietary risks previously discussed, see section 

5.4.4. 

7.2 Short-Term Aggregate Risk

Short-term aggregate risk assessments consider exposures that may occur between 1 and 30 days. 

To aggregate across routes of exposure, toxicity endpoints must be similar. The short-term 

dermal and inhalation endpoints are the same for adults; thus, these routes of exposure can be

aggregated. The short-term incidental oral and dermal endpoints are the same for children; thus 

these routes of exposure can be aggregated. For children, the aggregate assessment consists of 

average food and drinking water exposures plus incidental oral exposures and dermal exposure. 

For adults, the aggregate assessment consists of average food and drinking water exposures and 

dermal and inhalation exposure. The results from this assessment are presented below in Table 

7.2, and indicate that short-term aggregate risks are not of concern for fluazifop-P-butyl, since all 

short-term aggregate MOEs exceed the LOC of 100.

Table 7.2 Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure3

mg/kg/day

Residential 

Exposure 

mg/kg/day4

Total 

Exposure 

mg/kg/day5

Aggregate 

MOE (food, 

water, and 

residential)6

Adult 2 100 0.02 0.001104 0.0086 0.009704 210

Child 100 100 1 0.004756 0.0271 0.031856 3,100

1 LOC = 100 (10X interspecies uncertainty factor, 10X intraspecies uncertainty factor, 1X FQPA safety 

factor)

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Average Food and Water Exposure from Table 5.4.6 (chronic dietary)

4Residential Exposure = [Oral & dermal exposure (children)] (Table 6.3.1) 

5 Total Exposure = Avg Food & Water Exposure + Residential Exposure

6 Aggregate MOE = [NOAEL/ (Avg Food & Water Exposure + Residential Exposure)]
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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7.3 Intermediate-Term Aggregate Risk

All residential exposures are anticipated to be short-term in duration; thus, an intermediate-term 

aggregate risk assessment is not required.

7.4 Chronic Aggregate Risk

Chronic aggregate risks are identical to the chronic dietary risks previously discussed, see section 

5.4.4. No long-term residential exposures are anticipated for fluazifop-P-butyl.

8.0 Cumulative Exposure/Risk Characterization

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 fluazifop-P-butyl and any other substances and fluazifop-P-butyl does not appear to produce a 

toxic metabolite produced by other substances. For the purposes of this tolerance action, 

therefore, EPA has not assumed that fluazifop-P-butyl has a common mechanism of toxicity with 

other substances. For information regarding EPA’s efforts to determine which 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/.

9.0 Occupational Exposure/Risk Characterization

An updated occupational assessment is not required for this action.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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10.0 References

Table 10.0. Memoranda Relevant to Fluazifop-P-Butyl. 

Author Barcode Date Title

W. Donovan D426930 5/13/2015 Fluazifop-P-Butyl: Residue Chemistry Review for Sweet Potato Label 

Amendment and Resulting Tolerance Increase. Abbreviated Review.

W. Donovan D426145 3/31/2015 Fluazifop-P-Butyl: Acute and Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessments for the Sweet Potato Label 

Amendment and Resulting Increase in Tolerance Level.

J. Alsadek -- 3/27/2015 Usage Report in Support of Fluzifop (122809)

A. LaMay,

S. Dapson, and

W. Donovan

D421107 12/5/2014 Fluazifop-P-butyl. Human Health Risk Assessment Scoping Document in 

Support of Registration Review

S. Recore and 

E. Evans

D421768 8/5/14 Fluazifop-butyl and Fluazifop-p-butyl: Tier I Review of Human Incidents

W. Donovan D415419 6/18/2014 Fluazifop-P-Butyl: Review of Residue Chemistry Data Submitted as a 

Condition of Registration.

P. Savoia D385205 1/4/2011 Fluazifop-P-Butyl. Amended Section 3 Registration Request to Add New Uses 

on Bananas, Citrus, Grapes, and Sugar Beets. Summary of Analytical 

Chemistry and Residue Data.

P. Savoia D385178 1/4/2011 Revised Fluazifop-P-Butyl. Amended Human Health Risk Assessment to Support Use 

on Bananas, Citrus, Grapes, Sugar Beets, and the Establishment of a Tolerance on 

Imported Potatoes.

P. Savoia D372408 8/31/2010 Fluazifop-P-Butyl. Request for the Registration of a Reduced Pre-Harvest 

Interval for Application of the Venture L End-Use Product on Imported 

Potatoes. Summary of Analytical Chemistry and Residue Data.

D. Locke D316891 8/29/2005 Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment 

Eligibility Document (TRED). PC Code: 122809, Case # 2285, DP Barcode: 

D316891

S.L. Kinard, 

D. Anderson, 

and W.P. 

Eckel

TXR No. 

0052680

3/17/2004 Fluazifop-P-butyl. Report of the Metabolism Assessment Review Committee. 
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food-use for fluazifop-P-butyl are in Table 1. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 28-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

no

yes

yes

yes

yes

yes

870.3700a Developmental Toxicity (rodent) ..................................

870.3700b Developmental Toxicity (nonrodent) ............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

yes

yes

yes

yes

yes a

yes

yes b

yes

870.5100 Mutagenicity—Bacterial reverse mutation assay ....................

870.5300 Mutagenicity—In vitro mammalian cell gene mutation test.......

870.5375 Mutagenicity—In vitro mammalian chromosome aberration test

870.5395 Mutagenicity—Mammalian erythrocyte micronucleus test........

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

yes

yes

no

yes

yes

yes 

yes 

yes 

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

yes

yes 

a The combined chronic toxicity/carcinogenicity study in rats (OCSPP 870.4300) satisfies these requirements.

b An oncogenicity study in hamster satisfies the requirement for an oncogenicity study in a second species.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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A.2 Toxicity Profiles

Table A.2.1.a Acute Toxicity Profile – Fluazifop-Butyl a

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral - Rat 00162439 LD50 = 1940 

mg/kg (♂) ± 

1193-2758 mg/kg

LD50 = 2653 

mg/kg (♀) ± 

1764-3625 mg/kg

III

870.1200 Acute dermal - Rat 00162439 LD50 > 2 mL/kg 

(♂♀) or 

approximately 

2000 mg/kg

III

870.1300 Acute inhalation - Rat 46082901, 

same as 

41563701

LC50 > 2.3 mg/L 

for 43% with a 

particle size <5 

μm

LC50 >4.37 mg/L 

for 83% with a 

particle size <10 

μm

III

870.2400 Acute eye irritation - Rabbit 00088855 Non-irritating IV

870.2500 Acute dermal irritation - Rabbit 00088853 Mild erythema at 

72 hours

IV

870.2600 Skin sensitization - Guinea Pig 00088854 Not a dermal 

sensitizer

-

a Purity of 93.3-99.6% a.i.

Table A.2.1.b Acute Toxicity Profile – Fluazifop-P-Butyl a

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral - Rat 00162440 LD50 = 3680 

mg/kg for males 

LD50 = 2451 

mg/kg for females

III

870.1200 Acute dermal - Rat 00162440 LD50 > 2000 

mg/kg or >1.73 

mL/kg

III

870.1300 Acute inhalation - Rat 41917904 LC50 > 1.7 mg/L III

870.2400 Acute eye irritation - Rabbit 00162441 Mild irritation, 

cleared within 3 

days

IV

870.2500 Acute dermal irritation - Rabbit 00162441 Slight irritation,

cleared within 72 

hours

IV
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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870.2600 Skin sensitization - Guinea Pig 00162441 Not a dermal 

sensitizer

-

a Purity of 86.3-99.6% a.i., except acute inhalation. This study was conducted with a mixture of 24.6% fluazifop-pbutyl and 7.0% fenoxyprop-p-ethyl, however, the concentration fluazifop-p-butyl in the inhalation chamber was 

determined to be 1.7 mg/L. 

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100 90-Day oral 

toxicity (rat) with 

FB

00093820 (1980)

Acceptable, guideline

0, 10, 100, 2000 ppm

M: 0, 0.7, 7.1, 144.5

mg/kg/day

F; 0, 0.8, 8.0, 161.9

mg/kg/day

NOAEL= 0.7 mg/kg/day

LOAEL=7.1 mg/kg/day based on liver and 

kidney histopathology.

870.3100 90-Day oral 

toxicity (rat) with 

FPB

46158402 (1985)

Acceptable, guideline

0, 10, 100, 2000 ppm

F: 0, 0.5, 5, 100

mg/kg/day

NOAEL= 0.5 mg/kg/day

LOAEL=5 mg/kg/day based on decreased 

spleen weight and decreased hematological 

parameters in males. Dose related testicular 

weight decrement and cholesterol depression.

870.3100 90-Day oral 

toxicity (hamster) 

with FPB

46082902 (2001)

Acceptable, guideline

Males: 0, 19.5, 78.3 or 

291.9 mg/kg/day

Females: 0, 19.9, 79.0 or 

319.6 mg/kg/day

NOAEL = M/F: 78.3/79.0 mg/kg/day

LOAEL = M/F: 291.9/319.6 mg/kg/day based 

on decreased body weight/body weight gain 

and food efficiency in males and evidence of 

liver toxicity; centrilobular eosinophilia/loss of 

glycogen in males and females.

870.3150 90-Day oral

toxicity (dog) with 

FB

00093821 (1980)

Acceptable, guideline

0, 5, 25, 125/250

mg/kg/day

NOAEL = 25 mg/kg/day

LOAEL = 125/250 mg/kg/day based on 

multiple pathologies in 3 dogs (2 males and 1 

female) killed at 1 month dosed at 250 

mg/kg/day. Also seen were body weight loss 

gut lesions, severe eye lesions and 

hepatotoxicity. In remaining surviving dogs 

dosed at 125 mg/kg/day, mild to equivocal liver 

lesions were seen.

870.3200 21/28-Day dermal 

toxicity (rabbit) 

with FB

00093819 (1980)

Acceptable, guideline

0, 100, 500, 2000

mg/kg/day

NOAEL = 100 mg/kg/day

LOAEL = 500 mg/kg/day based on death in 1 

male and at 2000 mg/kg/day, death 4 males and 

5 females, possibly due to kidney failure.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3700a Prenatal 

developmental 

toxicity in 

Sprague Dawley 

rats with FB

00008857, 92067047

(1981)

Acceptable, guideline

0, 10, 50, 200 mg/kg/day

Maternal NOAEL = 200 mg/kg/day; LOAEL 

= None based on maternal weight decrement 

due to

gravid uterine weight decrement.

Developmental NOAEL=none; LOAEL=10 

mg/kg/day based on delayed ossification. At

200 mg/kg/day - diaphragmatic hernia.

870.3700a Prenatal 

developmental 

toxicity in 

Sprague Dawley 

rats with FB

00088858, 92067048,

92967020 (1981)

Acceptable, guideline

0, 1.0, 5.0, 10, 200

mg/kg/day

Maternal NOAEL=200 mg/kg/day; 

LOAEL=None based on maternal weight 

decrement partially explained by gravid urine 

weight decrement.

Developmental NOAEL=1 mg/kg/day; 

LOAEL=5 mg/kg/day based on fetal weight 

decrement and increased incidence of small 

fetuses and delayed ossification. At 200 

mg/kg/day - increased inc. of diaphragmatic 

hernia.

870.3700a Prenatal 

developmental 

toxicity in Wistar 

rats with FPB

46158401 (1991)

Acceptable, guideline

0, 0.5, 1.0, 20, 300

mg/kg/day

Maternal NOAEL=20 mg/kg/day; 

LOAEL=300 mg/kg/day based on body weight 

gain decrement.

Developmental NOAEL=1.0 mg/kg/day; 

LOAEL=20 mg/kg/day based on delayed 

ossification in skull bones, cervical arches and 

centrum in fetuses and litters and delayed 

ossification in the manus and pes.

870.3700a Prenatal 

developmental 

toxicity in Wistar 

rats with FPB

46082903 (1989)

Acceptable, guideline

0, 2, 5, 100 mg/kg/day

Maternal NOAEL=100 mg/kg/day; LOAEL= 

None based no maternal toxicity.

Developmental NOAEL=2.0 mg/kg/day; 

LOAEL=5.0 mg/kg/day based on based on 

dose related delayed ossification in skull bones 

[occipital and parietal] in fetuses and litters.

870.3700a Prenatal 

developmental 

toxicity in Wistar 

rats with FPB

46082013 (1990)

Acceptable, guideline

0, 2.0, 5.0, 100 mg/kg/day

Maternal NOAEL=100 mg/kg/day; LOAEL= 

None based on no toxic effects

Developmental NOAEL=2.0 mg/kg/day; 

LOAEL=5.0 mg/kg/day based on delayed 

ossification in skull bones, sternebrae bipartite, 

sternebrae and calcenum unossified in fetuses 

and litters

870.3700b Prenatal 

developmental 

toxicity in NZW 

rabbits with FB

00088856, 92067049,

92067021 (1981)

Acceptable, guideline

0, 10, 30, 90 mg/kg/day

Maternal NOAEL=30 mg/kg/day; LOAEL=90 

mg/kg/day based on abortions.

Developmental NOAEL=30 mg/kg/day; 

LOAEL=90 mg/kg/day based on nominal 

increases in delayed ossification, total litter 

loss, abortions, small fetuses, cloudy eyes all 

above mean or range of historical controls
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3700b Prenatal 

developmental 

toxicity in NZW 

rabbits with FPB

46082904 (1993)

Acceptable, guideline

0, 2, 10, 50 mg/kg/day

Maternal NOAEL=10 mg/kg/day; LOAEL=50 

mg/kg/day based death, abortions and body 

weight loss

Developmental NOAEL=10 mg/kg/day; 

LOAEL=50 mg/kg/day based on increased 

incidence of 13th rib and delayed ossification in 

sternebrae 2.

870.3800 Reproduction and 

fertility effects in 

rats with FB

00088859, 92067050

(1981)

Acceptable, guideline

0, 10, 80, 250 ppm

M/F: 0/0, 0.74/0.88,

5.8/7.1, 21.7/17.5

mg/kg/day

Parental/Systemic NOAEL = M/F 0.74/7.1 

mg/kg/day; LOAEL = M/F 5.8/ 21.7 mg/kg/day 

based on decreased spleen wt. in males & 

increased absolute & relative liver & kidney 

wts. & geriatric nephropathy in females.

Offspring NOAEL = 7.1 mg/kg/day; LOAEL 

= 21.7 mg/kg/day based on pup viability in f1 

and f2 pups during lactational day 1, 4, 11, 18 

& 25 and decreased f2 pup weight on 

lactational day 25.

Reproductive NOAEL = M/F - 0.74/0.88 

mg/kg/day; LOAEL = M/F - 5.8/7.1 mg/kg/day 

based on decreased abs. & rel testes & 

epididymal weight and in females decreased 

pituitary & uterine weights.

870.4100a Chronic toxicity

(rat)

Not submitted. See 

870.4300.

-

870.4100b Chronic toxicity -

dog with FB

00131462, 00131463,

92067018 (1982)

Acceptable, guideline

0, 5, 25, 125 mg/kg/day

NOAEL = 5 mg/kg/day; LOAEL = 25 

mg/kg/day based on marginally increased 

incidence adrenal fatty vacuolation & increased 

incidence of thymic involution and at 125 

mg/kg/day death of 4/6 males and 2/6 females, 

eye, gastrointestinal tract lesions, adrenal and 

bone marrow pathology & thymic involution

870.4200 Carcinogenicity

in hamsters with 

FPB

4534501, 46082905 

(2001) Acceptable, 

guideline

0, 0, 200, 750, 3000 ppm

M: 0, 0, 12.5, 47.4, 193.6 

mg/kg/day 

F: 0, 0, 12.1, 45.5, 181.4 

mg/kg/day

NOAEL = 12.1 mg/kg/day 

LOAEL = 45.5 mg/kg/day based on based on 

increased incidence of males with reduced 

sperm, testicular degeneration, eye cataract 

changes, liver inflammation and gall stones and 

in females, increased incidence of ovarian 

stroma cell/sex chord hyperplasia

No evidence of carcinogenicity
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.4300 Combined 

Chronic/

Carcinogenicity

in rat with FB

41563703 (1985) 

Acceptable, guideline

0, 2, 10, 80, 250 ppm 

M: 0, 0.10, 0.51, 4.15, 

12.3 mg/kg/day 

F: 0, 0.13, 0.65, 5.2, 16.0 

mg/kg/day

NOAEL = 0.51 mg/kg/day 

LOAEL = 4.15 mg/kg/day based on increased 

mortality and nephropathy exacerbated by 

respiratory stress 

No evidence of carcinogenicity 

Gene 

Mutation

870.5100

Ames/

Salmonella 

typhimurium, 

reverse mutation 

with FB (96.8% 

a.i.)

00162443, 92067023

Acceptable

Histidine deficient strains 

TA98, TA100, TA1535, 

TA1537, TA1538 of 

S. typhimurium were 

exposed in the presence 

and absence of 

mammalian metabolic 

activation by plate 

incorporation

Negative with and without S9 up to the limit 

dose of 5000 μg/plate.

Gene 

Mutation

870.5100

Ames/

Salmonella 

typhimurium,

reverse mutation 

with FPB (93.6% 

a.i.)

00162442, 92067013

Acceptable

Histidine deficient strains 

TA98, TA100, TA1535, 

TA1537, TA1538 of 

S. typhimurium were 

exposed in the presence 

and absence of 

mammalian metabolic 

activation by plate 

incorporation

Negative with and without S9 up to the limit 

dose of 5000 μg/plate (insoluble at 5000 

μg/plate).

Mammalian 

cell gene 

mutation 

assay 

870.5300

Mouse lymphoma 

cell test with FPB 

(99.6% a.i.) at 

concentrations of 

0, 0.25, 2.5, 25, 

250 or 2500 

μg/mL

00116678

Acceptable 

Heterozygous TK+/- P 

388 mouse lymphoma 

cells cultured in vitro 

were exposed in the 

presence and absence of 

mammalian metabolic 

activation, S9, for 30 

minutes.

Negative with and without S9 up to cytotoxic 

doses.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

Mouse 

lymphoma 

L5178Y 

TK+ test

870.5300

Mammalian cell 

gene mutation 

assay with FPB at 

0, 100, 200, 500, 

700, 1000 or 1500 

μg/mL and 0, 100, 

200, 500, 700 or 

1000 μg/mL

46082906

Acceptable

Mouse lymphoma 

L5178Y TK+ cells 

in vitro were exposed 4 hr 

with and without S9 

activation. In second 

assay the cells were 

exposed with and without 

S9 activation.

Negative with and without S9 activation up to 

and including excessive precipitation.

In vitro

chromosoma

l aberrations 

in human 

blood 

lymphocytes

870.5375

Mammalian cell 

cytogenetic assays 

(chromosome 

aberration) with 

FPB

(R-enantiomer, 

93.8% a.i.) in 

dimethyl sulfoxide 

at concentrations 

of 0, 1, 10, 100, 

500, or 1000 

μg/mL

41555202 (1985) 

Lymphocyte cultures 

prepared from human 

peripheral blood were 

exposed for 4 hours both 

in the presence and 

absence of S9-activation. 

Cells were harvested at 27 

hours after initiation of 

treatment.

Negative with no evidence of chromosome 

aberration induced over background in the 

presence or absence of S9-activation at toxic 

doses.

In vivo rat 

mammalian 

cytogenetics; 

bone 

marrow 

chromosoma

l aberrations

870.5385

Bone marrow 

chromosome 

aberration assays 

with FB (94.5% 

a.i.; Lot/Batch #: 

CTL Compound 

code: 

Y00083/001/006), 

in corn oil at 

doses of 0, 21.0, 

67.2, or 210.0 

mg/kg.

00088861 (1980)

Acceptable

10 male CD rats/dose 

were treated via oral 

gavage (10 mL/kg) either 

once (acute) or daily for 5 

consecutive days (subacute). Bone marrow cells 

were harvested at 6 or 24 

hours after treatment in 

the acute study, and at 6 

hours after treatment in 

the sub-acute study.

Negative with no evidence of chromosome 

aberration induced over background at toxic 

doses.

In vivo 

mouse 

micronucleus test 

870.5395

in vivo 

mammalian cell 

mouse 

micronucleus 

assay with FB or 

FPB at doses of 

250 or 400 mg/kg

00016244, 92068014 

(1983)

C57BL/6J mice - bone 

marrow removed after 24, 

48 or 72 hours to 

determine the frequency 

of MPCEP. FB and FPB 

were tested up to 80% and 

50% of the LD50 in mice.

Negative with no adequate evidence of a 

positive response of increased micronuclei over 

background with either fluazifop-butyl [FB] or 

fluazifop-P-butyl [FPB] at toxic doses.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

Page 35 of 38

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

Other 

Effects 

870.5900

sister 

chromatid 

exchange 

assay

Dominant lethal 

assay

[PP009, fluazifopbutyl (97.0% a.i.,)

at dose levels of 0, 

28.7, 91.8 or 287 

mg/kg/day in corn 

oil (10 mL /kg)

00088862 (1980)

Unacceptable 

25 CD-1 male mice/group 

treated for 5 days for the 

first mating. Based on the 

results of the first mating, 

subsequent matings were 

based on 15 of the 25 

dosed males. These 15 

males were mated with 30 

females in 8 sets and the 

females examined for 

dominant lethal effects 

(resorptions) at day 15 of 

pregnancy.

Top dose not sufficiently toxic. The 

investigators reported that fluazifop-butyl does 

not cause dominant lethal effects in CD-1 mice 

up to and including 287 mg/kg/day for 5 days. 

No toxicity demonstrated.

870.6100 Acute 

neurotoxicity in 

hens with FB

00093818 (1981) 

Acceptable, guideline

0, 3750, 7500, 15000

mg/kg

Fluazifop-butyl exposed hens showed no 

evidence of delayed neurotoxicity.

870.6200 Acute 

neurotoxicity 

screening battery -

rat

49188708 (2013)

Acceptable, guideline

0, 500, 1000, 2000 mg/kg

NOAEL was not observed

LOAEL = 500 mg/kg based on clinical signs 

indicative of toxicity (reduced activity, 

decreased rearing, hunched posture and/or 

piloerection), decreased body temperature, and 

decreased motor activity (total distance and 

number of rearings) in both sexes

870.6200 Subchronic 

neurotoxicity 

screening battery -

rat

49188705 (2013)

Acceptable, guideline

♂: 0, 100, 250, 1000 ppm 

♂: 0, 6.7, 16.8, 69.5 

mg/kg/day

♀: 0, 100, 250, or 4000 

ppm 

♀: 0, 7.9, 20.2, or 328.1 

mg/kg/day

NOAEL = 69.5 mg/kg/day

LOAEL was not observed in either sex

870.7485 Metabolism and 

pharmacokinetics 

in (rats) with FB

00093822 through 

00093828 (1981) 

Acceptable, guideline

1, 1000 mg/kg

Fluazifop-butyl is rapidly hydrolyzed to 

fluazifop acid by blood enzymes and excreted 

as the acid and its conjugates in the urine of 

males and females. Due to biliary excretion 

parent compound, fluazifop acid and its 

conjugates are excreted in the feces of males at 

much higher proportions than in feces of the 

female. Excretion was complete in 7 days, with 

the exception of small amounts in the fat in 

some rats.
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

Page 36 of 38

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Fluazifop-butyl [FB] and 

Fluazifop-P-butyl [FPB]

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.7600 Dermal 

penetration 

(human)

MRID 46082918 a human study/NG satisfies 

guideline 870.7600.

870.7800 Immunotoxicity 

(rat)

49188706 (2013)

Acceptable, guideline

♀: 0, 100, 500, 2000 ppm

♀: 0, 9, 44, 173

mg/kg/day

Systemic and immunotoxic NOAEL = 173 

mg/kg/day, the highest dose tested

Systemic and immunotoxic LOAEL were not 

observed
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

Page 37 of 38

Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Fluazifop-P-butyl.

Parameter Value Reference

Molecular Weight 383.37

Melting point/range Decomposes at 210 oC

164 oC at 0.02 mm Hg

2002 Farm Chemicals Handbook

RCB No. 1674, 2/3/87, L. Cheng

pH Not dispersible in water RCB No. 1674, 2/3/87, L. Cheng

Density 1.22 g/cc (PAI) and 1.20 g/cc (T) at 

20 oC

RCB No. 809, 6/3/86, L. Cheng

Water solubility 1 mg/L RCB No. 1674, 2/3/87, L. Cheng

Solvent solubility Soluble in most organic solvents

>500 g/L in acetone, dichloromethane, 

ethyl acetate, hexane, methanol, 

toluene, and xylene

2002 Farm Chemicals Handbook

RCB No. 1674, 2/3/87, L. Cheng

Vapor pressure 3 x 10-8 KPa at 20 oC RCB No. 809, 6/3/86, L. Cheng

Dissociation constant, pKa -3.1 (by calculation) RCB No. 809, 6/3/86, L. Cheng

Octanol/water partition coefficient, Log(KOW) 4.5 at 20 oC RCB No. 809, 6/3/86, L. Cheng
Fluazifop-P-butyl Human Health Risk Assessment DP No. D420423

Page 38 of 38

Appendix C. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Residential SOPs, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received 

that review, and (3) are compliant with applicable ethics requirements. For certain studies, the 

ethics review may have included review by the Human Studies Review Board. Descriptions of 

data sources, as well as guidance on their use, can be found at the Agency website5. 

In a metabolism study (MRID 00131464), fluazifop-butyl (99.6% a.i.) was administered to 3 

male humans in a single dose in corn oil on a sugar cube at a dose level of 0.07 mg/kg. The 

ethics of this human study was cleared in the memo “Ethics Review of Fluazifop-Butyl 

Absorption, Distribution and Metabolism Study” Sherman, 2010.

Human research was conducted as part of a dermal absorption study for fluazifop-P-butyl 

(MRID 46082918). The ethics of this study was cleared in the memo “Initial Ethics Review of a 

Human Study of Dermal Absorption and Pharmacokinetics of Fluazifop-Butyl” Lowe MF, 

Carley JM, June 10, 2006.

 

5 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html