UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: December 5, 2014 

OFFICE OF 

CIJEM ICAL SAFETY ANI> 

I)OLLl iTION PREVENTION 

SUBJECT: Fluazifop-P-butyl. Human Health Risk Assessment Scoping Document in 

Support of Registration Review 

PC Code: 122809 

Decision No.: 492472 

Petition No.: Not Applicable 

Risk Assessment Type: Single Chemical 

TXR No.: Not Applicable 

MRIO No.: None 

DP Barcode: D42ll07 

Registration No.: Not Applicable 

Regulatory Action: Registration Review Scoping 

Case No.: 2285 

CAS No.: 79241-46-6 

40 CFR: §1 80.411 

FROM: Alexandra LaMay, Risk Assessor (/ cit-~ ltVVJ,/ 

William Donovan, PhD., Chemist : (1'· {' ~ 

THRU: 

TO: 

Steve Dapson, PhD., Toxicologist ;~ V~ ~ 

Risk Assessment Branches V and VII ' · 

Health Effects Division (7509P) 

Office of Pesticide Programs 

Seyed Tadayon, Chemist 

Michael Metzger, Branch Chief 

Risk Assessment Branches V and 

Health Effects Division (7509P) 

Office of Pesticide Programs 

Matthew Manupella 

r 

Pesticide Re-evaluation Division (7508P) 

Office of Pesticide Programs 

Attached is the Health Effects Division's (HED) human health scoping document for fluazifop-P 

butyl to support the registration review process. 

Page 1 of27 
Executive Summary 

The Health Effects Division (HED) has evaluated the status of the human health risk assessment 

for fluazifop-P-butyl to determine the scope of work necessary to support registration review. 

The most recent human health risk assessment (D385 178, P. Savoia, 1/4/11 ) was considered as 

part of this seeping exercise. As noted in the previous assessment, 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. 

Fluazifop-P-butyl and fluazifop-butyl have low acute toxicity by the oral, dermal and inhalation 

routes, are mildly irritating to the eye and skin, and are not skin sensitizers. Subchronic and 

chronic toxicity studies with fluazifop-P-butyl or fluazifop-butyl show that the rat is more 

sensitive to toxic effects than the dog, rabbit or hamster, possibly due to longer retention time of 

the major metabolite (fluazifop acid) in the rat. 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. A subchronic inhalation study and a 90-day dermal 

toxicity study were identified as data gaps. 

The residue chemistry database for fluazifop-P-butyl is complete with the exception of a field 

rotational crop study. The confined rotational crop study showed that metabolite TFP is taken up 

by rotational crops. Thus, a field rotational crop study is required to determine if rotational crop 

tolerances are needed. 

Codex has not established fluazifop-P-butyl Maximum Residue Limits (MRLs) inion any 

commodity. Mexico generally adopts US tolerances and/or Codex MRLs for export purposes. 

Most of the Canadian MRLs are harmonized with the US tolerru:tces. However, higher residues 

in U.S. trials preclude harmonization for the following commodities: dry bean, cotton, and 

soybean. Evaluation of an amended use petition for sweet potato, currently in progress, may 

result in harmonization of the U.S tolerance and the Canadian MRL for this commodity. For 

grape, an increase in the US tolerance from 0.01 to 0.03 ppm would achieve harmonization and 

is recommended during registration review. HED is not currently involved in any joint 

international review projects that involve the active ingredient, fluazifop-P-butyl. 

Currently there are no acute or chronic dietary (food and drinking water) risk estimates which are 

of concern for fluazifop-P-butyl and its metabolites. However, updated dietary exposure 

assessments may be necessary under registration review if there are significant changes to the 

estimated drinking water concentrations (EDWCs) that will be updated by EFED, or if there are 

changes to the points of departure (PoDs) or uncertainty factors/safety factors (UFs/SFs). 

In residential settings, fluazifop-P-butyl is used on turf and ornamentals. Residential adult 

handler scenarios were previously assessed and are not of concern; combined dermal and 

inhalation MOEs range from 240 to 4300. Residential post-application exposure scenarios 

include dermal and non-dietary ingestion (hand-to-mouth, object-to-mouth, ingestion) exposure 

to children on treated lawns, dermal exposure to youths on treated golf courses, and dermal 

exposure to adults on treated lawns and on treated golf courses. All residential post-application 

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Page 3 of 27

MOEs were not of concern (MOEs > 100) for all populations. TTR data are required for 

fluazifop-P-butyl. An updated residential assessment may be required under registration review

to incorporate updated exposure assessment methodology for residential exposure scenarios.

Residential bystander exposures resulting from off-site transport (i.e., spray drift or 

volatilization) may occur as a result of occupational applications of fluazifop-P-butyl. The

potential for bystander exposure of fluazifop-P-butyl will be assessed during registration review.

In the most recent risk assessment, HED provided aggregate exposure and risk estimates for 

dietary and residential exposures. The exposure scenarios aggregated are: average dietary with 

short-term dermal and incidental oral exposure in infants and children; and average dietary with 

short-term dermal and inhalation exposure of adults. The combined MOE’s for the scenarios 

examined were below HED’s level of concern (i.e. MOE > 100). Aggregate exposures of 

fluazifop-P-butyl may be revised during registration review to consider new dietary and 

residential exposures estimates. 

Based on the previous occupational exposure assessment, all of the handler (dermal and 

inhalation) exposure risk estimates were not of concern with some level of PPE (i.e., engineering 

controls for mixer/loaders). There are no post-application worker exposure risk estimates of 

concern. DFR data are available for fluazifop-P-butyl; TTR data are required. The Worker 

Protection Standard (WPS) restricted entry interval (REI) for fluazifop-P-butyl is 12 hours. An

updated occupational exposure and risk assessment is likely required during registration review

to include all registered uses as well as to include any changes to policy or toxicological points 

of departure.

Introduction

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 currently registered for food/feed use on a variety 

of crops, as well as registered for use on lawns/turf, ornamentals, non-bearing trees and non-crop 

areas. Fluazifop-P-butyl is typically applied as a broadcast, banded, directed or spot treatment 

with handheld, ground, or aerial equipment. Applications are made as pre-plant, at-plant, postemergence applications.

HED has evaluated the most recent human health risk assessment for fluazifop-P-butyl to 

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

HED has also considered updates to its toxicity, exposure and usage databases, and the latest 

Agency science policy and risk assessment methodologies. 

The chemical structure, nomenclature, and the physical/chemical properties of fluazifop-P-butyl are 

presented in Attachment 1.

Hazard Identification/Toxicology
Page 4 of 27

A subchronic inhalation study and a 90-day dermal toxicity study were identified as data gaps in 

the 2011 risk assessment for fluazifop-P-butyl. These studies are still required. Therefore, the 

toxicology database for fluazifop-P-butyl and fluazifop-butyl is incomplete. 

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. 

Fluazifop-P-butyl herbicidal specificity is by inhibiting acetyl CoA carboxylase (a key enzyme in 

plant fatty acid synthesis and required for maintaining membranes in functioning condition). 

Fluazifop-P-butyl is not an eye or skin irritant in acute or 21-day dermal studies, and is not a skin 

sensitizer. The liver and kidney are the 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. There was no evidence of 

carcinogenicity in the rat with fluazifop-butyl or in the hamster for fluazifop-P-butyl. The 

hamster, instead of the mouse, was selected for the second carcinogenicity study because liver 

peroxisome proliferation more closely resembled what was found for human liver cells. There 

were no mutagenicity concerns for fluazifop-butyl or fluazifop-P-butyl. 

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. In contrast, there was no appropriate 

endpoint which correlated to a single dose identifiable for the general U.S. population. The 

short-term incidental oral endpoint was 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 

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

decreased testes, and epididymal weights in males along with decreased uterine and pituitary 

weights in females. In regard to the short-term dermal and inhalation endpoints used in this 

assessment, the developmental toxicity studies performed on rats were used as the basis for 

endpoint selection. These studies exhibited decreased fetal weights, as well as hydroureter and 

delayed ossification effects. Because oral NOAELs were selected for dermal and inhalation 

endpoints, dermal absorption factors, calculated from a dermal absorption and pharmacokinetic 

study in humans, of 2% for high exposures and 9% for low exposures were used for oral-dermal 

route-to route extrapolation, and inhalation hazard is assumed to be equivalent to oral hazard.

 

The toxicity database includes multiple developmental toxicity studies in rats and rabbits on 

fluazifop-butyl and/or fluazifop-P-butyl and a two-generation reproduction study in rats with 

fluazifop-butyl. There was no evidence of increased susceptibity following in utero exposure in 

rabbits or following pre and post-natal exposure in the reproduction study with rats. In the 

developmental toxicity study with rats, while there was quantitative evidence of increased 

susceptibility, 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
Page 5 of 27

The chronic dietary (food and drinking water) exposure assessments and residential exposure 

risk assessments are based on conservative models and/or reliable data and therefore, the agency 

is confident that it will not underestimate risk from exposure to these compounds. 

The FQPA Safety Factor was reduced to 1X since the toxicology and exposure databases are 

completed and there is no residual uncertainty for pre and or post-natal toxicity.

The ACN and SCN studies along with an immunotoxicity study are presently under review. 

See Attachment 2 for Toxicity Profile Tables and Attachment 3 for Toxicity Doses and 

Endpoints Selection Table.

Conclusions: The toxicology database is complete with the exception of the subchronic 

inhalation study and a 90-day dermal toxicity study, which are required.

Dietary Exposure

The residue chemistry database for fluazifop-P-butyl is complete with the exception of a field 

rotational crop study. The residues of concern for tolerance expression and risk assessment for 

fluazifop-P-butyl in plants, livestock and water were determined by the HED Metabolism 

Assessment Review Committee (MARC) (See Attachment 5).

No decision was reached regarding the residue of concern in rotational crops due to the lack of 

rotational crop studies at the time of the 2004 MARC meeting. A confined rotational crop 

(CRC) study was recently submitted and reviewed (D374519, D. Soderberg, 8/19/2010). This 

study showed that detectable levels of 5-trifluoromethyl-2-pyridone (TFP) were taken up by 

rotational crops. Because TFP was identified as a residue of concern in plants for risk 

assessment purposes based on the results of the CRC study, a field rotational crop study is now 

needed. 

A number of residue chemistry data deficiencies were identified in the fluazifop-P-butyl TRED 

(D319907, S.L. Kinard, 8/17/2005) and in more recent new use petitions. Syngenta has 

addressed these deficiencies with several data submissions that were evaluated by HED in 

abbreviated chemistry reviews (see References). Review of residue chemistry data submitted to 

address conditions of registration or DCI requests was recently completed (D415419, W. 

Donovan, 18-JUN-2014). This review indicated the need for an increased tolerance level for 

soybean seed and decreased tolerance levels for processed citrus commodities. While sweet 

potato already is a registered crop, the registrant submitted a label amendment request to reduce 

the PHI from 55 days to 14 days, and provided new sweet potato residue data. Adequate 

analytical methods are available for data collection and tolerance enforcement. Other than the 

field rotational crop study, no other residue chemistry data deficiencies have been identified for 

fluazifop-P-butyl. 

The most recent acute and chronic dietary (food) exposure assessments were conducted in support 

of a January 2011 fluazifop-P-butyl new use risk assessment (D379452, S. Tadayon, 08/09/2010). 
Page 6 of 27

The Dietary Exposure Evaluation Model (DEEM) analysis was performed using tolerance level 

residues and assuming 100% crop treated. The acute and chronic dietary (food) risk estimates were 

not of concern. The only population subgroup requiring acute dietary exposure assessment, 

Females 13-49 years old, occupied 13% aPAD at the 95th percentile of exposure. The most highly 

exposed population subgroup for chronic exposures was Children 1-2 years old, which occupied 

40% of the cPAD.

EFED (Environmental Fate and Effects Division) provided peak and average estimated drinking 

water concentrations (EDWCs); these EDWCs were incorporated directly into the DEEM 

analysis (D379452, S. Tadayon, 08/09/2010). EFED may update the drinking water assessment 

under registration review; if estimated EDWCs increase substantially, then a new dietary 

exposure assessment for food and water may be needed.

Conclusions: A field accumulation in rotational crops study is required in registration review. 

A new dietary assessment may be required if 1) there are any significant changes to toxicological 

PODs or uncertainty factors, or 2) EFED recommends higher EDWCs than the current values. 

Residential (Non-Occupational) Exposure

There are currently registered residential uses for fluazifop-P-butyl; it is registered for use on turf 

and ornamentals. There is a potential for non-occupational exposure to adults applying the 

chemical and to adults and children entering treated areas. 

Residential Handler Exposure

Exposure to residential handlers is possible during the residential use of fluazifop-P-butyl. All 

residential handler scenarios were previously assessed (D316891, 8/29/05 and D316892, 

4/22/05). The results indicate that all of the residential handler risks are not of concern [i.e.,

MOEs are all greater than the LOC of 100]. Combined dermal and inhalation MOEs range from 

240 to 4300 for residential handlers.

Since the previous assessment, the Health Effects Division’s 2012 Standard Operating 

Procedures for Residential Pesticide Exposure Assessment has updated exposure assessment 

methodology for residential exposure scenarios. An updated residential handler assessment will 

likely be needed under registration review as a result of these revisions.

Residential Post-application Exposure

Fluazifop-P-butyl can be used in many areas that can be frequented by the general population 

including residential areas (e.g., home lawns). As a result, adults and children can be exposed by 

entering these areas if they have been previously treated.

The residential post-application exposure scenarios include dermal and non-dietary ingestion 

(hand-to-mouth, object-to-mouth, ingestion) exposure to children on treated lawns, dermal 
Page 7 of 27

exposure to youths on treated golf courses, and dermal exposure to adults on treated lawns and 

on treated golf courses. 

The fluazifop-P-butyl postapplication MOE values were calculated for adults after applications 

to golf courses and lawns. All MOEs are >100 on the day of application; MOEs range from 380 

for dermal exposure via high contact activities on lawns to 26,000 for dermal exposure while 

mowing turf. The postapplication MOE values were calculated for youth following golf course 

applications of fluazifop-P-butyl; MOEs for youths were >100. Exposure to children was

calculated for postapplication risks following the application of fluazifop-P-butyl to lawns. All 

MOEs are greater than HED’s LOC of 100 on day 0; MOEs range from 260 for dermal exposure 

during high contact activities on turf to 26,000,000 for oral exposure via incidental soil ingestion.

Since the previous assessment, the Health Effects Division’s 2012 Standard Operating 

Procedures for Residential Pesticide Exposure Assessment has updated exposure assessment 

methodology for residential exposure scenarios, including adult and children exposure to treated 

turf. An updated residential postapplication assessment may be needed under registration review 

as a result of these revisions.

In accordance with 40CFR158, 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 data1, 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 40CFR TTR data to facilitate any necessary 

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

of turf transferable pesticide residues.

Residential Bystander Exposures

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

volatilization) may occur as a result of agricultural applications of fluazifop-P-butyl. 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. In terms of volatilization, the agency has developed a 

Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 

 

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

Studies. 10/23/2014,, Exposure Science Advisory Council 
Page 8 of 27

(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.

Conclusions: TTR data are required for fluazifop-P-butyl. An updated residential handler and 

postapplication assessment are likely needed under registration review to include updated 

exposure assessment methodology for residential exposure scenarios. The potential for spray 

drift will be assessed during registration review. Also, the volatilization screening analysis will 

be used during registration review to determine if data or further analysis are required for 

fluazifop-P-butyl.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate 

pesticide exposures and risks from three major sources: food, drinking water, and residential 

exposures. The acute and chronic aggregate risk assessments included food and drinking water. 

The short-term aggregate risk assessment included food, drinking water, and residential 

exposures. No intermediate-term aggregate risk assessment was conducted since all 

residential/recreational exposures are anticipated to be short-term in duration.

Acute and Chronic

The 2011 acute and chronic aggregate risk assessments included exposure to fluazifop-P-butyl

residues in food and water. Acute and chronic dietary risk estimates for food and drinking water 

exposure are below HED’s level of concern (<100% of the aPAD and cPAD).

Short-term

In 2011, a short-term aggregate risk assessment was completed for fluazifop-P-butyl. For adults, 

the short-term aggregate assessment combined the average food and drinking water exposures 

with handler (dermal and inhalation) and postapplication exposures on treated turf (dermal). For 

children, the short-term aggregate assessment combined the average food and drinking water 

exposures with postapplication dermal and incidental oral (hand-to-mouth, object-to-mouth, soil 

ingestion) from contact with treated turf. The assessments resulted in risk estimates that are 

below the HED’s level of concern (MOE < 100). The short-term aggregate MOE for adults was 

150 and for children was 250.

Conclusions: During registration review, updated aggregate assessments will likely be 

conducted as required to include any significant change that might occur for toxicological PODs, 

FQPA and other uncertainty factors, dietary exposure estimates, or residential exposure 

estimates. 

Occupational Exposure

Several occupational exposure scenarios were previously assessed (D385178, 1/4/11, P. Savoia; 

D347515, 9/18/08, P. Savoia). The uses assessed include dry beans, peanuts, soybeans, bananas, 
Page 9 of 27

citrus, grapes, sugar beets, and imported potatoes. Although the occupational assessments 

described did not include all registered crops, the major crop groups were assessed and generally 

cover the registered uses. 

Occupational handler and post-application scenarios were assessed as workers can become 

exposed to fluazifop-P-butyl at short- or intermediate-term durations through its use.

Occupational Handler Exposure

Occupational handler scenarios include exposure too fluazifop-P-butyl during mixing, loading, 

and application activities. Estimated risks for occupational handlers determined for short-

/intermediate-term exposures yielded total MOEs greater than 100, with some scenarios 

requiring additional personal protection above baseline (e.g., engineering controls for 

mixer/loaders). In reaching or exceeding the LOC of 100, the resulting MOEs indicate these risks 

are not of concern.

Recommended unit exposures for occupational handler assessments have generally been derived 

only from the Pesticide Handlers Exposure Database (PHED). However, recently both the 

Outdoor Residential Exposure Task Force (ORETF) and the Agricultural Handler Exposure Task 

Force (AHETF) have produced pesticide handler exposure monitoring data that the Agency is 

using in place of PHED (http://www.epa.gov/pesticides/science/handler-exposure-data.html). As 

more reliable data become available, the Agency will continue to replace existing data. 

Reviewers should incorporate new exposure monitoring data, as necessary, during registration 

review.

Conclusions: An updated occupational handler assessment is likely required under registration 

review to include all registered uses as well as to include any significant changes in exposure 

assessment methodology, toxicological PODs or uncertainty factors.

Occupational Post-application Exposure

Some uses are ground directed applications where no crop foliage is being treated. As a result, 

this post-application exposure and risk to occupational workers was not quantitatively assessed. 

However, certain applications made to crops where workers can come in contact with foliage 

were previously assessed; these risks are not of concern since the resulting MOEs were greater 

than or equal to 100.

DFR data are available on cotton (MRID 45243801, D279616). These data have been reviewed 

and found to be acceptable for risk assessment purposes. These data will be incorporated into an 

updated occupational post-application assessment during registration review as necessary.

Recommended transfer coefficients for occupational post-application assessments are derived 

from Agricultural Reentry Task Force (ARTF) exposure monitoring studies 

(http://www.epa.gov/pesticides/science/post-app-exposure-data.html). These transfer 

coefficients have been updated in 2012 based on a reanalysis and submission of new monitoring 
Page 10 of 27

data. Reviewers should incorporate new exposure monitoring data, as necessary, during 

registration review.

The Worker Protection Standard (WPS) Restricted Entry Interval (REI) for fluazifop-P-butyl is 

12 hours.

Conclusions: An updated occupational post-application assessment is likely required under 

registration review to include all registered uses as well as to include any significant changes in 

exposure assessment methodology, toxicological endpoints or points of departure, or uncertainty 

factors. 

Public Health and Pesticide Epidemiology Data

HED has evaluated the available incident data2and concludes that based on the low frequency 

and low severity of incident cases reported in both IDS and SENSOR-Pesticides, there does not 

appear to be a concern at this time that would warrant further investigation. The Agency will 

continue to monitor the incident information and if a concern is triggered, additional analysis 

will be included in the risk assessment.

Tolerance Assessment and International Harmonization

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”.

A summary of US tolerances for residues of fluazifop-P-butyl may be found in Attachment 4. 

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

commodity. Mexico generally adopts US tolerances and/or Codex MRLs for export purposes. 

Most of the Canadian MRLs are harmonized with the US tolerances. However, differences are 

noted for the following commodities: dry bean, cotton, grape, soybean, and sweet potato. For 

dry bean, cotton, and soybean, the US tolerances are higher than the corresponding Canadian 

MRLs based on residue levels found in the supporting field trial studies due to different use 

patterns and/or formulations. It will be determined during registration review if harmonization 

is possible.. Harmonization of the sweet potato MRL and tolerance may be possible as part of 

the sweet potato label amendment review currently in progress. For grape, an increase in the 

US tolerance from 0.01 to 0.03 ppm would achieve harmonization and is recommended during 

registration review.

 

2 Fluazifop-p-butyl: Tier I Review of Human Incidents. S. Recore, 8/5/14. D421768.
Page 11 of 27

International or Intergovernmental Work Sharing

HED is not currently involved in any joint international review projects that involve the active 

ingredient, fluazifop-P-butyl. Additionally, HED is unaware of any ongoing international 

assessments for fluazifop-P-butyl. 

Cumulative

Though OPP recognizes that there are compounds that have some structural similarity with 

fluazifop-P-butyl; specifically diclofop-methyl [DFM], fenoxaprop-ethyl [FPE], 

haloxyfopmethyl [HFM] and quizalofop-ethyl. After careful analysis, OPP has concluded that 

fluazifop-P-butyl, DFM, FPE, HFM and/or QFE do not have a common mechanism of toxicity 

by a common pathway within the framework of the Guidelines (FR 63 42031). When one 

progresses through the framework for the five pesticides, the five pesticides pass Step 1 and 2, 

but fail Step 3, the crucial step showing a common mechanism of toxicity by a common pathway 

(see Table 1 in RESPONSE TO PUBLIC COMMENTS. The Health Effects Division’s 

Response to Comments on EPA’s HED Chapter of the Fluazifop-P-butyl Tolerance 

Reregistration Eligibility Decision Document (12/10/04) and Related Documents. PC Code: 

122809. Case# 2285. DP Barcode D291902. Diana Locke. August 22, 2005). Therefore, risks for 

these five pesticides can not be cumulated. 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/.

Human Studies 

There are no fluazifop-specific human studies that require an ethics review at this time.

Data Requirements

The following data deficiencies were identified for fluazifop-P-butyl:

Toxicology: 

870.3250 90-Day Dermal Toxicity 

870.3465 90-Day/28-Day Inhalation Toxicity 

Residue Chemistry: 

860.1900 Field Accumulation in Rotational Crops

The confined rotational crop study showed that metabolite TFP is taken up by rotational crops. 

Thus, a field rotational crop study is required to determine if rotational crop tolerances are 

needed.

Occupational and Residential Exposure: 
Page 12 of 27

875.2100 Turf Transferable Residue Data

References

Table 1. Memoranda Relevant to Registration Review

Author Barcode Date Title

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

Condition of Registration.

P. Savoia D405418 12/19/2012 Fluazifop-P-Butyl. Coffee Processing Study Submitted in Response to the 

August 2005 Tolerance Reassessment Eligibility Document (TRED).

P. Savoia D377906 6/23/2011 Fluazifop-P-Butyl. Required Data Provided to Support the August 2005 

Tolerance Reassessment Eligibility Document. Summary of Analytical 

Chemistry and Residue Data.

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 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. Soderberg D374519 8/19/2010 Fluazifop-P-butyl. Syngenta’s Response to the Residue Data Requirements of 

Fluazifop-P-Butyl TRED and Fluazifop-P-Butyl Generic DCI.

S. Tadayon D379452 8/9/2010 Fluazifop-p- Butyl Acute and Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section 3 Registration Action to 

add uses on Banana, Plantains, Citrus, Grapes, Potato and Sugar beet.

S.L. Kinard D319907 8/17/2005 Fluazifop-P-butyl. REVISED TRED - Report on FQPA Tolerance 

Reassessment Progress and Interim Risk Management Decisions. Residue 

Chemistry Considerations. 

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. 

S. Recore and 

E. Evans

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

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 D347515 9/18/08 Fluazifop-P-Butyl. Amended Human Health Risk Assessment to Support Use on Dry 

Beans, Peanuts, and the Post-Bloom Application to Soybeans.

M. Collantes D316892 4/22/2005 Fluazifop-p-butyl: Revised Residential Exposure Assessment and Recommendations for 

the Tolerance Reassessment Eligibility Decision (TRED) Document

S. Recore D279616 6/10/2003 Fusilade® DX on Cotton: Dislodgeable Foliar Residue Study

Attachments

Attachment 1. Chemical Identity

Attachment 2. Toxicity Profile Tables

Attachment 3. Endpoint Tables
Page 13 of 27

Attachment 4. International Residue Limits Table

Attachment 5. Residues of Concern Table.
Page 14 of 27

Attachment 1. Fluazifop-P-butyl Chemical Identity 

Table A1.1. Fluazifop-P-butyl Nomenclature.

Compound

N

F3C

O

O

H

CH3

O

O

C4H9(n)

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)

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

Table A.1.2. Physicochemical Properties of Fluazifop-P-butyl.

Parameter Value Reference

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
Page 15 of 27

Attachment 2. Toxicity Profile Tables

Table A2.1a. Fluazifop-butyl Acute Toxicity Profile

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

870.1100 Acute oral – rat

(PP009; 97.2%)

00162439

(1983)

LD50 = 1940 mg/kg 

(males) ± 1193-2758 

mg/kg

LD50 = 2653 mg/kg 

(females) ± 1764-3625 

mg/kg

III

870.1200 Acute dermal - rabbit

(PP009; 97.2%)

00162439

(1983)

LD50 > 2mL/kg (males 

and females) or 

approximately 2000 

mg/kg

III

870.1300 Acute inhalation - rat

(PP009; 97%) 79/ISK034/387

46082901, 

same as 

41563701

(1979)

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

(PP009; 93.3%) 79/ILK9/068

00088855 

(1979)

Non-irritating IV

870.2500 Acute dermal irritation – rabbit 

(PP009; 93.3%) 79ILK8/056

00088853 

(1979)

Mild erythema at 72 

hours

IV

870.2600 Skin sensitization – guinea pig 

(PP009; 99.6%) 80/ILK026/349

00088854 

(1980)

Not a dermal 

sensitizer

Table A2.1b. Fluazifop-P-butyl Acute Toxicity Profile

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

870.1100 Acute oral – rat

(PP005; 93.7% & 86.3% )

00162440

(1984)

LD50 = 3680 mg/kg for 

males 

LD50 = 2451 mg/kg for 

female 

III

870.1200 Acute dermal - rabbit

(PP005; 93.7% & 86.3%)

00162440

(1984)

LD50 > 2000 mg/kg or 

>1.73 mL/kg

III

870.1300 Acute inhalation - rat

(PP005; 24.6%) CTL/P/3331a

41917904

(1991)

LC50 > 1.7 mg/L III

870.2400 Acute eye irritation - rabbit

(PP005; 86.3%) CTL/P/856

00162441

(1983)

Mild irritation, cleared 

within 3 days

IV

870.2500 Acute dermal irritation – rabbit 

(PP005; 86.3%) CTL/P/856

00162441

(1983)

Slight irritation, 

cleared within 72 

hours

IV

870.2600 Skin sensitization – guinea pig 

(PP005; 99.6%) 80/ILK026/349

00162441

(1983)

Not a dermal 

sensitizer

a This study was conducted with a mixture of 24.6% fluazifop-p-butyl and 7.0% fenoxyprop-p-ethyl, however, the 

concentration fluazifop-p-butyl in the inhalation chamber was determined to be 1.7 mg/L. PPOO9 was used to 

indicate the technical grade of fluazifop-butyl. PPOO5 was used to indicate the technical grade of fluazifop-P-butyl.
Page 16 of 27

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

Profile

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 (mouse)

No study available

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.

870.3465 90-Day inhalation 

toxicity (species)

Data Waiver will be presented to HASPOC.

870.3700 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.
Page 17 of 27

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

Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700 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.

870.3700 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.

870.3700 Prenatal 

developmental 

toxicity in Wistar 

rats with FPB

46082903 (1989)

Acceptable/guideline

0, 2, 5 or 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.

870.3700 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

870.3700 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

870.3700 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.
Page 18 of 27

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

Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

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.

870.4100 Chronic toxicity -

rat

870.4300 satisfies the requirement

870.4100 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 =M/F 12.5/12.1 mg/kg/day LOAEL = 

47.5/45.5 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

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 = M/F 0.51/5.2 mg/kg/day LOAEL = 

M/F 4.15/16.0 mg/kg/day based on increased 

mortality & nephropathy exacerbated by 

respiratory stress, and in females possible 

increased basal and/or follicular/luteal cysts. 

No evidence of carcinogenicity 

Gene 

Mutation

870.5100

Ames/

Salmonella 

typhimurium, 

reverse mutation 

with FB (96.8% 

a.i., batch/lot# P25

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.
Page 19 of 27

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

Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

Gene 

Mutation

870.5100

Ames/

Salmonella 

typhimurium,

reverse mutation 

with FPB (93.6% 

a.i., batch/lot# P8)

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., 

batch/lot # 

ADGM/1021/79) 

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.

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 to 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.

Test was negative with and without S9 

activation up to and including excessive 

precipitation.

In vitro 

chromosomal 

aberrations in 

human blood 

lymphocytes

870.5375

Mammalian cell 

cytogenetic assays 

(chromosome 

aberration) with 

FPB

(R-enantiomer, 

93.8% a.i.; CTL 

ref. # 

Y02746/001/008) 

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.

There was no evidence of chromosome 

aberration induced over background in the 

presence or absence of S9-activation at toxic 

doses.
Page 20 of 27

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

Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

In vivo rat 

mammalian 

cytogenetics; 

bone marrow 

chromosomal 

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.

There was 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.

There was 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.

Mouse 

Dominant 

lethal test 

870.5450

DNA damage in 

Bacillus subtilis

Other Effects 

870.5900

sister 

chromatid 

exchange 

assay

Dominant lethal 

assay

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

batch/lot # 310M)] 

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 or 15000 or 

15000 mg/kg

Fluazifop-butyl exposed hens showed no 

evidence of delayed neurotoxicity.

870.6200 Acute 

neurotoxicity 

screening battery -

rat

49188708 Under review
Page 21 of 27

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

Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.6200 Subchronic 

neurotoxicity 

screening battery -

rat

49188705 Under review

870.6300 Developmental 

neurotoxicity

Not required

870.7485 Metabolism and 

pharmaco-kinetics 

in (rats) with FB

00093822 through 

00093828 (1981) 

Acceptable/guideline 1 

mg/kg and 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.

870.7600 Dermal penetration MRID# 46082918 a human study/NG satisfies 

guideline 870.7600.

870.7800 Immunotoxicity 49188706 Under review
Page 22 of 27

Attachment 3. Fluazifop-P-butyl Endpoints and Doses for Risk Assessment

Table A3.1. Summary of Toxicological Doses and Endpoints for Fluazifop-P-butyl for Use in Dietary and 

Non-Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A 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 = 

0.50 

mg/kg/day

Developmental Toxicity in rats

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 

= 0.008

mg/kg/day

cPAD = 

0.0074 

mg/kg/day

Two-Generation Reproduction in rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased spleen, 

testes & epididymal weights in males and 

uterine & pituitary weights in females

Incidental 

Oral ShortTerm (1-30 

days)

NOAEL= 

100 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental Toxicity Study in rats

LOAEL = 300 mg/kg/day based on 

maternal body weight 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

Two-Generation Reproduction in rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased spleen, 

testes & epididymal weights in males and 

uterine & pituitary weights in females

Dermal 

Short-Term 

(1-30 days)a

(Females 13-

49)

NOAEL= 

2.0 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental Toxicity Study in rats

LOAEL = 5.0 mg/kg/day based on fetal 

weight, hydroureter and delayed 

ossification

Dermal 

Short-Term 

(1-30 days)a

(General 

Population 

including 

Infants & 

children)

NOAEL= 

100 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental Toxicity Study in rats

LOAEL = 300 mg/kg/day based on 

maternal body weight decrements during 

GD 7-16.
Page 23 of 27

Table A3.1. Summary of Toxicological Doses and Endpoints for Fluazifop-P-butyl for Use in Dietary and 

Non-Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

IntermediateTerm (1-6 

months)a

NOAEL=

0.74 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Two-Generation Reproduction in rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased spleen, 

testes & epididymal weights in males and 

uterine & pituitary weights in females

Inhalation 

Short- Term 

(1-30 days)b

(Females 13-

49)

NOAEL=

2.0 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental Toxicity Study in rats

LOAEL = 5.0 mg/kg/day based on fetal 

weight, hydroureter and delayed 

ossification

Inhalation 

Short- Term 

(1-30 days)b

General 

Population 

including 

Infants & 

children)

NOAEL=

100 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Developmental Toxicity Study in rats

LOAEL = 300 mg/kg/day based on 

maternal body weight decrements during 

GD 7-16.

Inhalation 

IntermediateTerm (1-6 

months)b

NOAEL= 

0.74 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Two-Generation Reproduction in rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased spleen, 

testes & epididymal weights in males and 

uterine & pituitary weights in females

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be carcinogenic to humans.”

a Use either 9% (low exposure scenario) or 2% (high exposure scenario) for route-to-route extrapolations

b Absorption via the inhalation route is presumed to be equivalent to oral absorption.

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. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. 
Page 24 of 27

Table A3.2. Summary of Toxicological Doses and Endpoints for Fluazifop-P-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

UFA=10x

UFH=10x

Occupational LOC 

for MOE = 100

Developmental Toxicity Study in rats

LOAEL = 5.0 mg/kg/day based on fetal 

weight, hydroureter and delayed 

ossification

Dermal 

IntermediateTerm (1-6 

months)

NOAEL=

0.74 

mg/kg/day

UFA=10x

UFH=10x

Occupational LOC 

for MOE = 100

Two-Generation Reproduction in 

rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased 

spleen, testes & epididymal weights in 

males and uterine & pituitary weights 

in females

Inhalation 

Short-Term (1-

30 days)

NOAEL=

2.0 

mg/kg/day

UFA=10x

UFH=10x

Occupational LOC 

for MOE = 100

Developmental Toxicity Study in rats

LOAEL = 5.0 mg/kg/day based on fetal 

weight, hydroureter and delayed 

ossification

Inhalation 

Intermediateterm (1-6 

months)

NOAEL=

0.74 

mg/kg/day

UFA=10x

UFH=10x

Occupational LOC 

for MOE = 100

Two-Generation Reproduction in 

rats

LOAEL = 5.8 mg/kg/day in males and 

7.1 in females based on decreased 

spleen, testes & epididymal weights in 

males and uterine & pituitary weights 

in females

Cancer (oral, 

dermal, 

inhalation)

Classification: “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.
Page 25 of 27

Attachment 4. Fluazifop-P-butyl International Residue Limits Table

Table A4. Summary of US and International Tolerances and Maximum Residue Limits : Fluazifop-P-butyl 

(PC Code 122809) 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.411:

Plants and livestock: sum of fluazifop-Pbutyl, butyl(R)-2-[4-[[5-(trifluoromethyl)-2-

pyridinyl]oxy]phenoxy]propanoate, and the 

free and conjugated forms of the resolved 

isomer of fluazifop, (R)-2-[4-[[5-

(trifluoromethyl)-2-

pyridinyl]oxy]phenoxy]propanoic acid, 

calculated as the stoichiometric equivalent of 

fluazifop

butyl (RS)-2-[4-[[5-(trifluoromethyl-2-

pyridinyl]oxy]

phenoxy]propanoate (calculated as acid)

None

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

US Canada Mexico2 Codex

Banana 0.01

Beans, dry, seed 50 0.15 Dry (adzuki beans, beans, blackeyed 

peas, broad beans, catjang seeds, chickpeas, 

cowpea seeds, guar seeds, kidney beans, 

lablab beans, lima beans, moth beans, mung 

beans, navy beans, pink beans, pinto beans, 

rice beans, southern peas, tepary beans, urd 

beans, grain lupin

1 dry soybeans 

Beet, sugar, dried pulp 1.0

Beet, sugar, molasses 3.5

Beet, sugar, roots 0.25

Carrot, roots 2.0 2

Cattle, fat 0.05 0.05

Cattle, meat 0.05 0.05

Cattle, meat byproducts 0.05 0.05

Citrus, dried pulp 0.40

Citrus, juice 0.06

Citrus, oil 30.0

Cotton, gin byproducts 1.5

Cotton, refined oil 1.3 0.2 

Cotton, undelinted seed 1.0 0.1

Egg 0.05 0.05

Endive 6.0

Fruit, citrus, group 10 0.03

Fruit, stone 0.05 0.05 apricots, fresh prune plums, nectarines, 

peaches, plumcots, plums, sweet cherries, 

tart cherries

Goat, fat 0.05 0.05

Goat, meat 0.05 0.05

Goat, meat byproducts 0.05 0.05

Grape 0.01 0.03

Hog, fat 0.05 0.05

Hog, meat 0.05 0.05
Page 26 of 27

1 No US registration 

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

(c) Tolerances with regional registrations. Tolerances with regional registrations are established for residues of the 

herbicide fluazifop-P-butyl, including its metabolites and degradates, in or on the following commodities in the table. 

Compliance with the tolerance levels specified in the table below is to be determined by measuring only the sum of 

fluazifop-P-butyl, butyl(R)-2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoate, and the free and conjugated 

forms of the resolved isomer of fluazifop, (R)-2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoic acid, 

calculated as the stoichiometric equivalent of fluazifop, in or on the commodity.

Commodity Parts per million Canada

Asparagus 3.0 3

Coffee, bean 0.1 0.1 green coffee beans

Pepper, tabasco 1.0

Rhubarb 0.5 0.5

Hog, meat byproducts 0.05 0.05

Horse, fat 0.05 0.05

Horse, meat 0.05 0.05

Horse, meat byproducts 0.05 0.05

Milk 0.05 0.05

Nut, macadamia 0.10 0.1

Onion, bulb 0.50 0.5

Peanut 1.5 1.5

Peanut, meal 2.2

Pecans 0.05 0.05

Poultry, fat 0.05 0.05

Poultry, meat 0.05 0.05

Poultry, meat byproducts 0.05 0.05

Potato1 1.0 1

Potato, chips1 2.0 2

Potato, granules/flakes1 4.0 4

Sheep, fat 0.05 0.05

Sheep, meat 0.05 0.05

Sheep, meat byproducts 0.05 0.05

Soybean, seed 2.5 1 dry soybeans

Sweet potato, roots 0.05 0.5

MRLs with NO US Equivalent

Blueberries 0.1

Flaxseeds 0.2

Mustard 0.3

Non-bell peppers 1

Solin 0.2

Strawberries 1

Completed: M. Negussie; 07/22/14
Page 27 of 27

Attachment 5. Fluazifop-P-butyl Residues of Concern.

Table A5. Fluazifop-P-Butyl Residues of Concern in Plants, Livestock, Rotational Crops and Water.

Residues of Concern

Matrix For Tolerance Expression For 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)

Rotational Crops No decision1 No decision2

Water NA Parent and fluazifop acid

1 Parent and fluazifop acid (free and conjugated).

2 Parent and fluazifop acid (free and conjugated), and 5-trifluoromethyl-2-pyridone.