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6.2 Postapplication Exposure ............................................................................................ 21

6.3 Combined Exposure..................................................................................................... 22

6.4 Residential Bystander Postapplication Inhalation Exposure................................... 23

6.5 Spray Drift.................................................................................................................... 23

7.0 Aggregate Exposure/Risk Characterization.................................................................. 24

7.1 Acute Aggregate Risk................................................................................................... 24

7.2 Short-Term Aggregate Risk ........................................................................................ 24

7.3 Chronic Aggregate Risk .............................................................................................. 25

8.0 Cumulative Exposure/Risk Characterization ............................................................... 25

9.0 Occupational Exposure/Risk Characterization ............................................................ 25

9.1 Short-/Intermediate-Term Handler Risk................................................................... 26

9.2 Short and Intermediate -Term Postapplication Risk ............................................... 27

9.2.1 Dermal Postapplication Risk ................................................................................... 27

9.2.2 Inhalation Postapplication Risk .............................................................................. 27

Appendix A. Toxicology Profile and Executive Summaries .................................................. 29

A.1 Toxicology Data Available for Fluroxypyr........................................................................ 29

A.2 Toxicity Profiles............................................................................................................ 30

Appendix B. Review of Human Research............................................................................... 35
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1.0 Executive Summary

HED has conducted a human health risk assessment for the herbicide, fluroxypyr for the purpose 

of establishing tolerances for a proposed new use on rice as requested by Dow Agrosciences 

LLC. 

The proposed use directions specify that fluroxypyr is to be applied by broadcast ground and 

aerial application to the rice field at a maximum single application rate of 0.24 lb ae/A (0.34 lbs 

ai/A). Two applications per season are permitted with a 60-day preharvest interval (PHI). 

The kidney is the target organ for fluroxypyr (and fluroxypyr MHE) following oral exposure to 

rats, mice, and dogs. There was no evidence of increased susceptibility following in utero 

exposure to the acid and the ester in rats and rabbits, or following pre and/or postnatal exposure 

to the acid form in rats. Neither developmental toxicity nor reproductive toxicity was observed in 

rats. In rabbits, developmental toxicity was not observed following exposure to fluroxypyr, but 

abortions were observed in rabbits following exposure to fluroxypyr MHE at the limit dose. 

There was no evidence of neurotoxicity or neuropathology in any study. There were no 

treatment-related effects in an immunotoxicity study in rats. Fluroxypyr is classified “not likely

to be carcinogenic to humans” and there is no concern for its mutagenicity potential. 

Endpoints for risk assessment were based on kidney effects. Doses selected for risk assessment 

purposes are summarized below. The FQPA safety factor was reduced to 1X since the toxicity 

database was considered complete, there were no residual uncertainties for pre-and/or post natal 

toxicity, no evidence of neurotoxicity or neuropathology was found, and the estimated exposures 

were not likely to underestimate risk.

An acute dietary risk assessment was not required as there were no effects seen in the database 

which could be attributable to exposure to a single dose of fluroxypyr. Chronic dietary exposure 

and risk assessments were conducted assuming 100% crop treated and tolerance level residues 

for all existing and new uses of fluroxypyr. Modeled drinking water estimated environmental 

concentrations (EECs) were incorporated into the chronic dietary risk assessment. No chronic 

dietary risks of concern were identified for the U.S. population or any subgroup. The most 

highly exposed subpopulation was infants (< 1 year) with an estimated risk equivalent to 3.5% of 

the chronic population adjusted dose (cPAD). A quantitative dietary cancer risk assessment was 

not required.

There were no new residential uses requested in this petition. The existing residential uses have 

been assessed using the new residential SOP (01/01/2012) and all calculated residential MOEs 

were greater than the target of 100, and therefore, were not of concern to HED.

Human health aggregate risk assessments were conducted for the chronic aggregate exposure 

(food + drinking water) scenario, as well as the short-/intermediate-term aggregate exposure 

scenario. Short-, intermediate- and chronic aggregate risks were not of concern.
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Occupational handler and post application exposures and risks were evaluated for the proposed 

new use on rice. MOEs for all scenarios exceeded the target MOE of 100 and were not of 

concern. 

This risk assessment does not rely on any toxicity data from studies in which human subjects 

were intentionally exposed to a pesticide or other chemical. The ORE assessment used generic 

exposure data from exposure studies that have been subject to OPP ethics review and have been 

approved for use in human health risk assessments.

2.0 HED Recommendations

HED has no objection to establishment of the proposed tolerances shown below or to registration 

of the new use of fluroxypyr on rice.

2.1 Data Deficiencies/Conditions of Registration

There are no data gaps with respect to toxicology, residue chemistry, or occupational exposure 

for fluroxypyr.

2.2 Tolerance Considerations

Tolerances are established for the residues of the herbicide fluroxypyr, including its metabolites 

and degradates, under 40 CFR 180.535. Compliance with the established tolerance levels is 

determined by measuring only the sum of fluroxypyr 1-methylheptyl ester [1-methylheptyl ((4-

amino-3, 5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate] and its metabolite fluroxypyr [((4-amino3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid] calculated as the stoichiometric equivalent of 

fluroxypyr. The established tolerances for plant commodities range from 0.02 ppm (field corn 

grain, sweet corn K+CWHR, and sorghum grain) to 160 ppm (grass hay) [40 CFR 180.535(a)]. 

The established tolerances for livestock commodities range from 0.1 ppm (fat, meat, and meat 

byproducts) to 1.5 ppm (kidney). Time-limited tolerances for combined residues of fluroxypyr 

1-MHE and its metabolite fluroxypyr in/on field corn, sweet corn, onion, and sorghum 

commodities have been established in connection with use of fluroxypyr 1-MHE under Section 

18 emergency exemptions [40 CFR 180.535(b)]; time-limited tolerances have past due expiration 

dates (12/31/05 and 12/31/06), except for onion with an expiration date of 06/30/07.

2.2.1 Enforcement Analytical Method

Adequate GC/ECD (gas chromatography/electron capture detection) analytical methods are 

available to enforce the proposed plant tolerances. The available methods for plant commodities 

involve extraction of fluroxypyr residues with acetone, partitioning with hexane, purification 

using a Florisil column, and analysis of residues by GC/ECD.

2.2.2 International Harmonization

There are no Maximum Residue Limits (MRLs) established by Codex, Canada, or Mexico for 

any of the proposed commodities in the current registration action (Section 3). 
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2.2.3 Recommended Tolerances

Permanent tolerances are established under 40 CFR §180.535(a) for the combined residues of

fluroxypyr 1-MHE and its metabolite fluroxypyr on a number of plant and livestock 

commodities. Tolerances are already set on most of the representative crops listed for the cereal 

grains crop group 15 (sweet corn, field corn, sorghum & wheat), and the forage, fodder, and 

straw of cereal grains crop group 16 (corn & wheat) except for rice. To support this registration, 

Dow has submitted field trial data and a processing study for rice. For this petition request, Dow 

is proposing that permanent tolerances be established for the residues of fluroxypyr in/on the 

following rice commodities:

Rice ..........................................................................1.5 ppm

Rice, bran .................................................................3.0 ppm

2.3 Label Recommendations

No label revisions are needed and no recommendations are being made by HED.

2.3.1 Recommendations from Occupational Assessment

No label revisions are needed based on the occupational exposure risk assessments. 

2.3.2 Recommendations from Residential Assessment

No recommendations are needed based on HED’s residential exposure and risk assessment.

3.0 Introduction

Fluroxypyr is a member of the pyridinoxy acid class of herbicides. Other chemicals in this class 

include triclopyr, picloram, and clopyralid. Fluroxypyr induces auxin-type responses in 

susceptible annual and perennial broadleaf weeds. The pesticide active ingredient is fluroxypyr

methylheptyl ester (fluroxypyr MHE). The end-use products are emulsifiable concentrate 

formulations of fluroxypyr 1-methylheptyl ester (fluroxypyr 1-MHE), with a maximum single 

application rate of 0.24 lb acid equivalents (a.e.) or 0.34 lb ai/ per acre. 
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3.1 Chemical Identity

Table 3.1. Fluroxypyr 1-MHE Nomenclature.

Compound

Common name Fluroxypyr 1-methylheptyl ester

Company experimental name XRM-5316

IUPAC name 1-methylheptyl-4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetate

CAS name [(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid, 1-methylheptyl ester

CAS # 81406-37-3

End-use product/EP 1.5 lb ae/gal EC formulation (StaraneTM Herbicide; EPA Reg. No. 62719-286) 

Fluroxypyr, free acid

Common Name Fluroxypyr

CAS name [(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid

CAS # 69377-81-7

3.2 Physical/Chemical Characteristics

Table 3.2. Physicochemical Properties of the Fluroxypyr 1-MHE.

Parameter Value

Melting point/range 57.5°C 

pH 6.81 in solution containing 90.1 μg/L

Density 1.30 g/mL at 21°C

Water solubility ( 20 °C) 90.1 μg/L in purified water

294 μg/L in pH 5 buffer

136 μg/L in pH 7 buffer

57.2 g/L in pH 9 buffer

Solvent solubility (20 °C) 6.23 g/100 mL in n-heptane

>200 g/100 mL in xylene

377 g/100 mL in methanol

22.0 g/100 mL in n-octanol

>300 g/100 mL in acetone

Vapor pressure 2.0 x 10-5kPa at 25 °C

1.0 x 10-5kPa at 20 °C

Dissociation constant Not applicable

Octanol/water partition coefficient Log(KOW) 4.57 at pH 5

5.04 at pH 7

5.31 at pH 9

UV/visible absorption spectrum Not available

F N

Cl Cl

NH2

O O

CH3

CH3

F N

Cl Cl

NH2

O

OH

O
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3.3 Pesticide Use Pattern 

The herbicide fluroxypyr-1-methylheptyl ester is currently registered for use in or on field corn, 

sweet corn, sorghum, range and pasture grasses, turf, dry bulb onions, garlic, pome fruits and 

shallots. Current petition is to establish tolerances for fluroxypyr on rice and rice bran. The most 

recent risk assessment was performed for the proposed uses of fluroxypyr on pome fruits and 

shallots (Donna S. Davis, 2007; D344540). Fluroxypyr is registered for use on residential 

turfgrass and recreational sites, such as golf courses, parks, and sports fields. The summary of 

purposed use pattern is presented in Table 3.3.

Table 3.3 Summary of Purposed Use Patterns/Formulation Information

Crop Trade Name Number of Application 

per Season

Max Application 

lb ai/A. per 

Season

Max. Single 

Application lb ai/A

PHI

Rice Starane UltraTM Herbicide 2 0.57 0.34 60

3.4 Anticipated Exposure Pathways

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

proposed new use of the herbicide fluroxpypyr on rice. Fluroxpypyr is currently registered for 

use on field corn, and there are tolerances for residues in crop group 15 (cereal grains) and crop 

group 16 (forage, fodder and straw of cereal grains) and livestock commodities. Therefore, 

humans may be exposed to fluroxpypyr in food and drinking water, since the chemical may be 

applied directly to growing crops and may reach surface and ground water sources of drinking 

water. While the products containing fluroxpypyr do not appear to be intended for homeowner 

use, there is the potential for homeowners to purchase and apply the product to their own lawns, 

and the potential for this exposure has been considered in the risk assessment. In an 

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

application (i.e., mixing/loading), as well as during application. There is the potential for 

postapplication exposure to workers re-entering treated fields, but since there is no dermal 

endpoint (toxicity) associated with fluroxypyr, there are no human health concerns for risk by 

this route of exposure.

Risk assessments have been previously prepared for the existing use of fluroxypyr on residential 

turf (K. O’Rourke, D328799, 07/06/2006). This risk assessment considers all exposure pathways 

based on the existing and proposed new use of fluroxypyr.

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

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

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

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

and activities in and around the home that involve pesticide use in a residential setting. 
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Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

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

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

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

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

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

exposures 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 toxicology database is complete. The Fluroxypyr Risk Assessment Team has reviewed the 

toxicity database and concluded that the doses and endpoints previously selected for risk 

assessment purposes are consistent with current HED policy and are appropriate for the routes 

and durations of exposure anticipated from the existing and newly proposed uses of fluroxypyr. 

4.1 Toxicology Studies Available for Analysis

The toxicology database on fluroxypyr, which includes studies on both fluroxypyr and 

fluroxypyr methylheptyl ester) is sufficient for assessing the toxicity and characterizing the 

hazard of fluroxypyr. The toxicology studies for fluroxypyr and fluroxypyr methylheptyl ester 

are summarized in Table A.1 in Appendix A. The database includes the following studies. 

Acute/lethality studies (oral, dermal, inhalation, primary eye and dermal irritation, and 

dermal sensitization) –fluroxypyr and fluroxypyr MHE

Subchronic oral toxicity studies (rat, mouse, and dog) - fluroxypyr

Developmental (rat and rabbit) and reproductive (rat) toxicity (oral) studies –fluroxypyr 

and fluroxypyr MHE

Dermal (21-day) toxicity (rabbit) study - fluroxypyr MHE

Chronic oral toxicity studies (rat and dog) - fluroxypyr

Carcinogenicity (oral) studies [rat (chronic combined) and mouse] - fluroxypyr

Metabolism study (rat) - fluroxypyr MHE

Mutagenicity battery - fluroxypyr MHE

Immunotoxicity study (rat) - fluroxypyr

The studies available for consideration of fluroxypyr toxicity provide a comprehensive database, 

with routes of administration which are consistent with potential exposure scenarios. 
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4.2 Absorption, Distribution, Metabolism, and Elimination (ADME)

Radiolabeled fluroxypyr methylheptyl ester (MHE) was readily absorbed and rapidly eliminated 

following a single oral dose to male Fischer 344 rats. Approximately 90% of the administered 

dose was absorbed. Once absorbed, it was extensively metabolized (≈20 metabolites) and rapidly 

expired as 14CO2 or eliminated in the urine, primarily as metabolites. Peak plasma concentrations 

were attained by 7 hours, and the half-live for the elimination phase was ≈18 hours. 

Approximately 7% of the administered dose was found in the carcass and ≈0.14% was found in 

the blood. 

4.2.1 Dermal Absorption

No dermal absorption studies are available. A dermal absorption factor is not required since 

quantification of dermal risk is not required based on lack of toxicity observed in the dermal 

toxicity study, and the lack of pertinent effects in other toxicity studies not measured in the 

dermal toxicity study.

4.3 Toxicological Effects

The kidney is the target organ for fluroxypyr following oral exposure to rats, mice, and dogs. In 

the rat, increased kidney weight, nephrotoxicity, and death were observed in both sexes in the 

90-day feeding study, and increased kidney weight and chronic progressive 

glomerulonephropathy were observed in both sexes in the chronic study. Increased kidney 

weight was observed in maternal rats in the developmental toxicity study with fluroxypyr, and 

kidney effects (deaths due to renal failure; increased kidney weight, and microscopic kidney 

lesions) were observed in both sexes in the 2-generation reproduction study in rats. Although 

kidney toxicity (early signs of acute tubular nephrosis) was observed in dogs in the 28-day 

feeding study, no kidney effects or other treatment related toxicity were seen in the chronic 

feeding study in dogs at the same doses used in the 28-day study. Kidney lesions (increased 

incidences of renal papillary necrosis and regenerative nephrosis in females) were observed in 

mice following long-term exposure. 

There was no evidence of increased susceptibility (quantitative/qualitative) following in utero 

exposure to the acid and the ester in rats and rabbits, or following pre and/or postnatal exposure 

to the acid form in rats. Neither developmental toxicity nor reproductive toxicity was observed in 

rats. In rabbits, developmental toxicity was not observed following exposure to fluroxypyr at 

dose levels that resulted in maternal death. Abortions were observed in rabbits following 

exposure to fluroxypyr MHE at the limit dose. There was no evidence of neurotoxicity or 

neuropathology in any of the studies. An immunotoxicity study in rats found no indication of 

immunotoxicity. Fluroxypyr is classified “not likely to be carcinogenic to humans”, and there is 

no concern for its mutagenicity potential. 

Fluroxypyr has low acute toxicity by the oral and dermal routes of exposure and moderate acute 

toxicity by the inhalation route of exposure, based on lethality studies. Fluroxypyr (MHE) ester 

is less acutely toxic than the acid by the oral route of exposure. Neither chemical is irritating to 

the skin. Fluroxypyr MHE is not a dermal sensitizer; however, it is a mild eye irritant. The 
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acute toxicity profiles for fluroxypyr and fluroxypyr MHE technical are contained in Attachment 

1 of this risk assessment. 

The toxicity profile of fluroxypyr and fluroxypyr 1-MHE technical is shown in Attachment 2 of 

this risk assessment. 

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

HED recommends that the 10X FQPA Safety Factor (for the protection of infants and children) 

be reduced to 1X. An FQPA Safety Factor of 1X is appropriate for the following reasons:

The toxicity database is complete and adequate to assess safety for infants and children. There is 

no evidence of increased qualitative or quantitative susceptibility in the developmental rat and 

rabbit studies or in the rat 2-generation reproduction study. These studies have clearly defined 

NOAEL/LOAELs. Both the neurotoxicity screening battery and the developmental 

neurotoxicity study have been waived. The exposure assessment will not underestimate 

children’s exposure to fluroxypyr. Further details may be found in the following sections.

4.4.1 Completeness of the Toxicology Database

The toxicology database for fluroxypyr is complete.. Acceptable developmental toxicity studies 

in rats and rabbits are available for fluroxypyr and fluroxypyr MHE, in addition to an acceptable 

reproduction study for fluroxypyr in rats. The HED’s Hazard and Science Policy Council

(HASPOC) determined that the acute and subchronic neurotoxicity studies may be waived.

4.4.2 Evidence of Neurotoxicity

There is no evidence of neurotoxicity or neuropathology in the available studies. The salivation 

and ataxia seen in animals prior to death were considered to be agonal; the salivation in the rat 

studies occurred following gavage dosing and was attributed to localized irritation; the decreased 

brain weight in the 90-day rat study was not substantiated in other studies. There is not a concern 

for developmental neurotoxicity.

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

There is no evidence of increased qualitative or quantitative susceptibility following in utero 

exposure to the acid and the ester in rats and rabbits or following pre and/or postnatal exposure 

to the acid in rats. 

Fluroxypyr is neither a developmental nor a reproductive toxicant in rats. Fluroxypyr has been 

evaluated for potential developmental effects in the rat and rabbit (gavage administration). 

Maternal toxicity included death in rats and rabbits. There were no developmental effects in the 

rat, and while abortions were observed in the rabbit, they occurred only at the limit dose.

The Fluroxypyr Risk Assessment Team reviewed the toxicity database and HIARC 

recommendations for consistency with current policy and reaffirmed the previous assessment 
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that the FQPA SF could be reduced to 1X based on the following considerations:

The toxicological database is considered complete.

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

There was no evidence of neurotoxicity or neuropathology in the available studies and 

the neurotoxicity battery (acute and subchronic) and developmental neurotoxicity study 

requirements have been waived.

The chronic dietary food exposure assessment utilizes tolerance level residue estimates 

and assumes 100 % CT for all commodities. This assessment will not underestimate 

exposure/risk.

The dietary drinking water assessment utilizes water concentration values generated by 

model and associated modeling parameters which are designed to provide conservative, 

health protective, high-end estimates of water concentrations which will not be exceeded.

The previous residential exposure assessment was conducted using standard assumptions 

and is not likely to underestimate exposure.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the fluroxypyr database in regard to dietary (food and

drinking water), occupational, and residential exposures. The residue data used for dietary 

exposure assessment are described in Section 5.4.1 of this document. Further, occupational and 

residential exposure estimates are based on conservative, health-protective assumptions that also 

ensure exposures are not underestimated. 

4.5 Toxicity Endpoint and Point of Departure Selections

The available hazard database is adequate to characterize any potential for prenatal or postnatal 

risk for infants and children. 

4.5.1 Dose-Response Assessment

The studies used for selecting toxicity endpoints and points of departure (PoDs) for various

exposure scenarios are presented in Appendix A.A2. The exposure profile includes all routes 

and durations of exposure, but based on the proposed use patterns for fluroxypyr, the expected 

exposure profile will be for chronic dietary, inhalation and incidental oral exposures. 

While the description of the toxicity studies used for selecting toxicity endpoints and points of 

departure for various exposure scenarios is presented in Appendix A, the following outlines the 

dose-response assessment and a general description of the endpoint selection. A summary of the 

endpoint and point of departure selections for fluroxypyr is shown in Tables 4.5.4.1 and 4.5.4.2. 

Acute Dietary Endpoint: An acute endpoint was not identified. No adverse effects were 

identified following a single oral dose, and there are no developmental or neurotoxicity concerns 

noted in the database.
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Chronic Dietary Endpoint: The chronic endpoint was selected from the chronic/carcinogenicity 

study in rats (NOAEL= 100 mg/kg/day; LOAEL= 500 mg/kg/day), based on kidney effects that 

include increased kidney weights, alterations in clinical chemistry parameters indicative of 

impaired renal function, and an increase in the severity of chronic progressive 

glomerulonephropathy in both sexes. The NOAEL/LOAEL are supported by the kidney effects 

observed in male rats in the 2-generation reproduction study (increased kidney weights with 

corresponding gross and microscopic kidney findings, including papillary atrophy, edema, 

necrosis, hyperplasia of the pelvic epithelium, degeneration/regeneration of the tubular 

epithelium, tubule-interstitial nephritis, and dilatations of the tubules). Although a lower 

NOAEL (50 mg/kg/day) was observed in a 28-day oral toxicity study in dogs (acute tubular 

necrosis), the finding was not replicated in the chronic dog study at the same dose levels that 

were tested in the 28-day study, and no other toxicity was observed in the chronic dog study. 

Short- and Intermediate-Term Incidental Oral Endpoints: 

The incidental oral endpoint was selected from the chronic/carcinogenicity study in rats 

(NOAEL= 100 mg/kg/day; LOAEL= 500 mg/kg/day), based on kidney effects that include 

increased kidney weights, alterations in clinical chemistry parameters indicative of impaired 

renal function, and an increase in the severity of chronic progressive glomerulonephropathy in 

both sexes. This dose/endpoint would address the nephrotoxicity concern for these exposure 

periods since signs of nephrotoxicity were observed in both sexes of rats after 90 days of 

exposure. Although a lower NOAEL was observed in the 90-day rat study (80 mg/kg/day), the 

apparent difference in NOAELs is attributed to dose-spacing (LOAEL 750 mg/kg/day). The 28-

day dog study also was not selected due to the low confidence in this study (2 dogs/sex were 

tested; the results were not replicated in the 1-year dog study; and no other toxicity was observed 

in the chronic study). 

Short- and Intermediate-Term Dermal Endpoints: No dermal endpoint was selected because no 

dermal or systemic toxicity at the limit dose was observed in the dermal toxicity study in rabbits, 

and there was no concern for developmental toxicity in rats or rabbits. The developmental 

toxicity observed in the rabbit occurred at the limit dose. Also, there was no evidence of 

progression of nephrotoxicity in the rat since the NOAELs/LOAELs were comparable between 

the subchronic and chronic toxicity studies. 

Short- and Intermediate-Term Inhalation Endpoint: The most appropriate endpoint for nonoccupational and occupational inhalation exposure was determined to be from the chronic oral 

toxicity study in rats (NOAEL=100 mg/kg/day; LOAEL=500 mg/kg/day), based on kidney 

effects that include increased kidney weights, alterations in clinical chemistry parameters 

indicative of impaired renal function, and an increase in the severity of chronic progressive 

glomerulonephropathy in both sexes. Although a point of departure obtained from a study 

conducted via the most relevant route of exposure is preferred for risk assessment, there is no 

repeat exposure inhalation toxicity study on fluroxypyr. HED waived the requirement for the 28-

day inhalation toxicity study, based on a weight of evidence (WOE) approach (TXR No. 

0056397) that considered the entire available hazard and exposure information for fluroxypyr.
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The level of concern for the relevant non-occupational and occupational exposure scenarios is an 

MOE of less than 100, based on the standard uncertainty factors for intraspecies variation (10X) 

and interspecies extrapolation (10X). 

Long-Term Dermal and Inhalation Endpoints: No long-term exposure scenarios exist for 

fluroxypyr.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Dermal exposure was not quantitatively assessed due to a lack of toxicity via the dermal route. 

Since adults were assessed for potential inhalation exposure while applying fluroxypyr to lawns, 

this exposure should be combined with background levels in food and water to determine 

aggregate exposure. For children’s residential exposure, only oral postapplication exposure was 

assessed, and this exposure should be combined with exposure from food and drinking water to 

determine aggregate exposure. For occupational workers, only inhalation exposure and risk were 

assessed.

4.5.3 Cancer Classification and Risk Assessment Recommendation

Under the revised 2005 Agency cancer assessment guidelines, fluroxypyr is classified as “not 

likely to be a human carcinogen.” There were no treatment-related increases in the incidence of 

tumors in either the rat or mouse carcinogenicity studies, both of which were tested at adequate 

doses.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Tables 4.5.4.1 and 4.5.4.2 summarize the points of departure and toxicity endpoints used in the 

dietary/non-occupational and occupational human health risk assessments, respectively.
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Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Fluroxypyr for Use in 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

(All populations)

No adverse effects were identified following a single oral dose and there are no developmental 

concerns noted in the database.

Chronic Dietary

(All populations)

NOAEL= 100 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1x

chronic RfD = 

1 mg/kg/day

chronic PAD= 

1 mg/kg/day

Chronic/Carcinogenicity-Rat

LOAEL = 500 mg/kg/day, based on kidney 

effects (increased kidney weights, 

alterations in clinical chemistry parameters 

indicative of impaired renal functions, and 

increase in severity of chronic progressive 

glomerulonephropathy in both sexes).

Incidental Oral

(Short- and 

Intermediate 

Term)

NOAEL= 100 

mg/kg/day

UFA 10x

UFH 10x

FQPA SF = 1x

Residential 

LOC is for 

MOE below 

100 

Chronic/Carcinogenicity-Rat

LOAEL = 500 mg/kg/day, based on kidney 

effects (increased kidney weights, 

alterations in clinical chemistry parameters 

indicative of impaired renal functions, and 

increase in severity of chronic progressive 

glomerulonephropathy in both sexes).

Dermal 

(Short- and 

Intermediateterm)

Quantification not required since 21-Day dermal rabbit NOAEL = 1000 mg/kg/day, and there are 

no developmental toxicity concerns.

Dermal 

(Long-term)

Long-term dermal exposure is not expected based on the current use pattern.

Inhalation 

(All durations)

Oral study 

NOAEL= 100 

mg/kg/day 

(inhalation and 

oral toxicity 

assumed to be 

equivalent)

UFA 10x

UFH 10x

FQPA SF = 1x

Residential 

LOC is for 

MOE below 

100 

Chronic/Carcinogenicity-Rat

LOAEL = 500 mg/kg/day, based on kidney 

effects (increased kidney weights, 

alterations in clinical chemistry parameters 

indicative of impaired renal functions, and 

increase in severity of chronic progressive 

glomerulonephropathy in both sexes). 

Cancer (oral) Classified as a “Not Likely” human carcinogen.

UF = uncertainty factor, FQPA SF = Food Quality Protection Act safety factor, NOAEL = no observed adverse 

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

chronic), RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable
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Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Fluroxypyr for Use in 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

Inhalation 

(All durations)

Oral study 

NOAEL= 100 

mg/kg/day 

(inhalation and 

oral toxicity 

assumed to be 

equivalent)

UFA 10x

UFH 10x

FQPA SF = 1x

Occupational 

LOC is for 

MOE below 

100 

Chronic/Carcinogenicity-Rat

LOAEL = 500 mg/kg/day, based on kidney 

effects (increased kidney weights, 

alterations in clinical chemistry parameters 

indicative of impaired renal functions, and 

increase in severity of chronic progressive 

glomerulonephropathy in both sexes). 

Cancer (oral) Classified as a “Not Likely” human carcinogen.

UF = uncertainty factor, FQPA SF = Food Quality Protection Act safety factor, NOAEL = no observed adverse 

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

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

5.0 Dietary Exposure and Risk Assessment 

A chronic dietary exposure analysis was performed for the purposes of this human health risk 

assessment (Fluroxypyr Chronic Dietary (Food and Drinking Water)), (S. Tadayon, D405555, 

09/11/12). 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

There have been no new data submitted with respect to metabolism in plants and livestock. HED 

previously concluded that the nature of the residue is adequately understood based on studies in 

corn, in rotational crops and in livestock. The residue of concern includes the parent fluroxypyr 

1-MHE and its acid metabolite, fluroxypyr. 

5.1.2 Summary of Environmental Degradation

Degradation of fluroxypyr –MHE and fluroxypyr in environmental fate laboratory studies occurs 

through base-catalyzed hydrolysis and microbial-medicated metabolism under aerobic 

conditions. In sterilized buffered water, fluroxypyr –MHE hydrolyzed to the fluroxypyr acid 

with half lives of 3 and 454 days at PH 9 and 7, respectively. Hydrolysis of fluroxypyr-MHE 

was not observed in the acidic test system at PH 5. In the aerobic soil metabolism study, 

microbial degradation of fluroxypyr-MHE appears to follow a biphasic degradation pattern with 

an initial first order half life of 1-3 weeks in four soils. The rate of metabolism decreased 

significantly after 2 months. Fluroxypyr and fluroxypyr –MHE degrade rapidly in the aerobic 

aquatic environment (half life 14 days). Fluroxypyr and fluroxypyr-MHE do not degrade by 

photolysis in aqueous environments or in soil. Volatility is not a significant rout of dissipation.
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5.1.3 Comparison of Metabolic Pathways

The metabolism of fluroxypyr 1-MHE in plants is similar in wheat, onions, and broad-leaved 

weeds. Metabolism involves cleavage of the ester to the acid, followed by conjugation of the 

acid. Cleavage of the ether linkage to yield the pyridinol metabolite was insignificant. The 

primary route of uptake is through the plant cuticle, and other forms of uptake (i.e., via the roots) 

are less significant. The petitioner presented the metabolic summary for fluroxypyr MHE shown 

below and taken directly without alteration from MRID 47017103.

In addition to weed metabolites, rice roots may also be exposed to soil degradates of fluroxypyr. 

An aerobic soil metabolism study demonstrated that fluroxypyr 1-MHE is rapidly hydrolyzed to 

the acid, though not completely as some of the ester remained more than 5 months after 

application. Mineralization to CO2 was a significant route of degradation in the soil. Two soil 

metabolites were formed: pyridinol and methoxypyridine. The confined rotational crop studies 

(30-day PBI (plant back interval) with wheat, lettuce and turnips) demonstrated that the two soil 

metabolites were present at ≤0.01 ppm fluroxypyr acid equivalents in lettuce and turnip tops, and 

not present in wheat grain. Free or conjugated fluroxypyr acid was the most commonly observed 

residue and fluroxypyr 1-MHE was not detected at levels >0.01 ppm fluroxypyr acid equivalents.

5.1.4 Residues of Concern Summary and Rationale

The residues of concern for tolerance setting and risk assessment purposes in plants and livestock 

commodities are fluroxypyr 1-MHE and its metabolite fluroxypyr, free and conjugated, all 

expressed as fluroxypyr as shown in Table 5.1.4. The rationale for inclusion of these compounds 
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in the residue of concern is as follows. Fluroxypyr is the major residues in plants. In livestock, 

very low levels of residue transfer to tissues were seen, and fluroxypyr was the sole residue 

identified in livestock tissues. Further, the analytical enforcement method includes a hydrolysis 

step and detects the combined residues of parent and acid, expressed as fluroxypyr equivalents. 

Lastly, the parent and acid are considered to be of equal toxicity (DP #: D402134, Peter Savoia, 

09/11/2012). 

Table 5.1.4. Summary of Metabolites and Degradates to be included in the Risk Assessment 

and Tolerance Expression.

Matrix Residues Included In Risk 

Assessment

Residues Included In 

Tolerance Expression

Plants Primary Crops Fluroxypyr 1-MHE and 

Fluroxypyr, free and conjugates

Fluroxypyr 1-MHE and 

Fluroxypyr, free and 

conjugates

Rotational 

Crops

Livestoc

k

Ruminant Fluroxypyr 1-MHE and 

Fluroxypyr, free and conjugates

Fluroxypyr 1-MHE and 

Fluroxypyr, free and 

conjugates

Poultry & 

Eggs

Drinking Water Fluroxypyr 1-MHE, Fluroxypyr Not Applicable

5.2 Food Residue Profile

Currently the use of fluroxypyr is limited to application to cereal grains and a new use on rice is 

proposed in this action. Fluroxypyr is applied post-emergent and consequently, significant 

residues are seen in forages of grains and rice. The plant metabolism data indicate translocation 

of residues throughout the plant and field trial data support this, as low, but quantifiable residues 

are seen in cereal grains and rice. Transfer of residues to livestock through consumption of 

treated feed items may occur. Low levels are expected in meat, meat by products, and fat. The 

highest residues are expected in kidney.

5.3 Water Residue Profile

The proposed new use label for application to rice permits a single maximum application of 0.34 

lb ai per acre per year and allows for two applications with a maximum total of 0.568 lb ai per 

acre per year with a minimum retreatment interval (RTI) of ten days. The label also requires a 

pre-harvest interval (PHI) of 60 days of harvest. This assessment reflects a high-exposure 

scenario by assuming the maximum application amount of 0.568 lb ai/A (0.64 kg/ha) is used per 

year.

Tier 1 Rice Model (v1), When using the Tier 1 rice model, EFED assumes pesticide application 

to a static rice paddy with no inflow from rainfall or outflow from seepage, overflow or 

evaporation. The only process simulated by the model is partitioning of the applied chemical 

between the 10-centimeter deep water column and the 1-centimeter deep sediment layer of the 

paddy. The partitioning is based on the pesticide’s Kd. Degradation in the paddy is not calculated 

by the model so the pesticide is assumed to remain at the initial concentration in the water 
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indefinitely. Results of the tier 1 rice modeling are presented in Table 5.3. Acute and chronic 

values are equal because the model does not simulate degradation of the pesticide in the paddy.

Table5.3. Summary of Tier 1 Rice Model EDWC for Use on Rice

Assessment Type Acute EDWC Chronic EDWC

Tier 1 Rice Model (conc in paddy) 540 μg/L (ppb) 540 μg/L (ppb)

5.4 Dietary Risk Assessment

Memo, S.Tadayon, 09/11/2012, D405555

5.4.1 Description of Residue Data Used in Dietary Assessment

For this analysis existing and recommended tolerance levels were used, as well as 100% crop 

treated (CT) assumptions for all commodities. DEEM (Version 7.81) default processing factors 

were used for most processed commodities that do not have individual tolerances. The existing

tolerances for livestock commodities were considered adequate (DP #: D405555, S. Tadayon, 

09/11/2012.

Drinking water was incorporated directly into the dietary assessment using the maximum chronic 

concentration for surface water generated by the Rice Model (v1) at 540 ppb. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

The chronic dietary exposure assessments based on food and drinking water includes the 

assumption of 100% crop treated (PCT) for all existing and proposed uses. 

5.4.3 Acute Dietary Risk Assessment

There was no appropriate endpoint identified for assessing acute dietary exposure; therefore, no 

acute dietary risk assessment was performed.
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5.4.4 Chronic Dietary Risk Assessment

An unrefined chronic dietary analysis for fluroxypyr was conducted using tolerance level 

residues and 100% crop-treated (CT) for all existing and proposed crop uses. Fluroxypyr 

chronic dietary (food + drinking water) exposure estimates using the DEEM-FCIDTM software 

are below HED’s level of concern for the U.S. population and each of the population subgroups. 

Chronic dietary exposure was 1.5% of the cPAD for the general U.S. population. The chronic 

dietary exposure for the highest reported exposed population subgroup, all infants (<1 year old), 

was 3.5% of the cPAD. The results of the analysis indicate that chronic risk from the dietary 

(food + drinking water) exposure to fluroxypyr will not exceed HED’s level of concern for the 

general U.S. population, nor any other population subgroups.

The results of the chronic dietary exposure analysis are reported in the Summary Table 5.4.5.

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Fluroxypyr.

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

N/A N/A

0.01476 1.5

N/A N/A

All Infants (< 1 year old) 0.03514 3.5

Children 1-2 years old 0.03286 3.3

Children 3-5 years old 0.02411 2.4

Children 6-12 years old 0.01597 1.6

Youth 13-19 years old 0.01124 1.1

Adults 20-49 years old 0.01367 1.4

Adults 50+ years old 0.01312 1.3

Females 13-49 years old 0.01349 1.3

*Population subgroups with the highest exposure are shown in bold.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Memo, M.Lloyd, 09/11/2012, D402132

There are no proposed residential uses in this petition; however, there are existing residential turf 

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

SOPs along with policy changes for body weight assumptions. 
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A product containing fluroxypyr (i.e., VistaTM) is registered for application to residential 

turfgrass and recreational sites such as golf courses, parks, and sports fields. It may be applied to 

turf at rates ranging from 0.125 to 0.47 lbs ai/A, but may not exceed 0.47 lbs ai/A/yr. The label 

does not prohibit homeowners from mixing/loading/applying VistaTM. 

6.1 Residential Handler Exposure

The residential handler assessment only quantitated the inhalation exposure route because there 

were no toxicity findings for the dermal route of exposure up to the limit dose, and there are no 

developmental effects of concern. 

The maximum application rate is used for assessing risk estimates for all exposure scenarios

(Table 6.1). All risk estimates have MOEs significantly greater than 100 (ranging from 3,800 to 

1,500,000) and are not of concern. 

Table 6.1. Short-Term Residential Handler Exposure and Risk Estimates for Application of Fluroxypyr on Residential Turf.

Exposure Scenario Application 

Rate a

Area Treated 

Daily b

Baseline Inhalation 

Unit Exposure b

Baseline Dose d Baseline 

Inhalation MOE e

lb ai/A Acres/gallons mg/lb ai mg/kg/day

Manually-pressurized Handwand 0.47 5 0.018 0.0034 30,000

Hose-end Sprayer 0.47 0.5 0.022 0.000065 1,500,000

Backpack 0.47 5 0.14 0.026 3,800

a Application Rates based on maximum application rates of registered residential turf uses for fluroxypyr: Starane Ultra (EPA Reg. No. 6217-

577).

b Based on HED’s SOPs: Lawns/Turf (January 2012). 

c Baseline Inhalation: no respirator. 

d Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/gal) x area treated (Acres/day) x absorption factor (%) / body 

weight (80 kg). No inhalation absorption factor.

e MOE = NOAEL (ST Inhalation NOAEL = 100 mg/kg/day) / daily dose (mg/kg/day). Level of concern = 100.

6.2 Postapplication Exposure

Post-application exposure can result from a number of activities following pesticide applications 

on turf. Exposure may occur for people of all ages, adults, children 11 < 16 years old, children 6 

< 11 years old, and children 1 < 2 years old. These populations are considered the index 

lifestages for lawns and turf depending on the exposure scenario. Young children 1 to <2 years 

old may receive incidental oral post-application exposure to fluroxypyr from treated turf. The 

postapplication exposures for children playing on treated turf resulting in incidental oral 

exposure as a result of mouthing behaviors were assessed using the new residential lawn/turf 

SOP (1/1/2012).

Although adults and children performing physical activities on treated turf (e.g. golfing, 

mowing) may also receive dermal exposure to fluroxypyr residues, a quantitative risk assessment 

for the dermal route of exposure was not conducted for reasons previously described. In 

addition, a quantitative postapplication inhalation exposure assessment was not conducted

because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (9.27 x 

10-7 mm Hg) and the relatively low proposed use rate (0.47 lb ai/A). The low application rate and 

vapor pressure; the inhalation assessment for handlers is protective of potential postapplication 

exposure and risk.
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The MOEs for incidental oral scenarios are summarized in Tables 6.2. The MOEs ranged from 

14,000 to 6,500,000 for incidental oral ingestion. All assessed residential exposures and risk 

estimates resulted in MOEs of > 100; and therefore, are not of concern to HED. 

Table 6.2. Children’s Short-term Non-Dietary Ingestion Fluroxypyr Exposure and Risk Estimate

Lifestage Post-Application Exposure Scenario Dose MOEs mg/kg/day

Emulisiable Concentrate (EC) Liquid Formulation

GF-2764 (EPA Reg. No. 62719-577) 3 lb ae/gallon

max single application rate: 0.47 lb ae/A

Child 1 to < 2 year old

Hand to Mouth 0.0070 14,000

Object to Mouth 0.00022 460,000

Incidental Soil Ingestion 0.000015 6,500,000

Hand-to-Mouth Dose = hand residue loading (mg/cm2) x fraction of hand mouthed (0.127) x surface area of 1 hand (150 cm2) x 

exposure time (1.5 hrs/day) x # of replenishment intervals/hr (4 int/hr) x (1-((1-saliva extraction factor (0.5))^(Number of handto-mouth events per hour (13.9 events/hr)/# of replenishment intervals/hr)) / body weight (11 kg).

Object-to-Mouth Dose = object residue loading (μg/cm2) * unit conversion factor (0.001 mg/μg) * object surface area mouthed / 

event (10 cm2/event) * exposure time (1.5 hrs/day) * # replenishment intervals/hr (4 int/hr) * (1-((1- saliva extraction factor 

(0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) / # replenishment intervals/hr)) / body weight (11 kg).

Soil Ingestion = soil residue (μg/g) * ingestion rate (50 mg/day) * conversion factor (0.000001 g/μg) / body weight (11 kg).

6.3 Combined Exposure

HED combines risk values resulting from separate exposure scenarios when it is likely they can 

occur simultaneously based on the use pattern and the behavior associated with the exposed 

population. In evaluating combined residential uses of fluroxypyr, HED reviewed all residential 

sources of exposure which consisted of: 1) adult inhalation handler (lawns only) exposure, and 2) 

child postapplication oral exposure. 

Since a dermal endpoint was not selected for fluroxypyr, the only route of exposure for which 

risks were quantified for adults is through the inhalation route, and therefore, a combined 

residential exposure assessment is not applicable. 

For children, because of the high-end assumptions used in each incidental oral scenario (hand to 

mouth, object to mouth, and soil ingestion), the exposures from these scenarios are not 

combined; rather, the highest (typically hand to mouth exposure) is used to assess aggregate risk, 

as described below. Since dermal and inhalation risks were not quantified, no post-application 

children’s risks were combined.

Table 6.3 identifies the residential scenarios and MOEs for adults and children for use in 

performing an aggregate exposure assessment as part of the fluroxypyr human health risk 

assessment. There are no risks of concern.
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Table 6.3. Summary of Residential Exposure and Risk Estimates.

Scenario

Daily Dose 1

MOE 2

mg/kg/day

Adults 

Residential Handler Inhalation Exposure

(Backpack) 0.026 3,800

Children

Post-Application Incidental Oral Exposure: Hand-to-Mouth

(After Liquid Application to Turf) 0.0070 14,000

1 Daily Dose = See Table 6.1 for adult handler scenarios and Table 6.2 for post-application incidental oral 

scenarios.

2 MOE = NOAEL/Daily Dose (mg/kg/day). ST Inhalation = 100; ST Incidental Oral = 100 mg/kg/day. LOC = 100.

6.4 Residential Bystander Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for fluroxypyr at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (9.27 x 10-7 mm Hg) and the 

relatively low proposed use rate (0.47 lb ai/A). However, volatilization of pesticides may be a 

potential source of postapplication inhalation exposure to individuals nearby to 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 is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

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

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative postapplication inhalation exposure assessment 

for fluroxypyr. Although a quantitative residential postapplication inhalation exposure 

assessment was not performed, an inhalation exposure assessment was performed for residential 

handlers. This exposure scenario is representative of a worse case inhalation exposure and 

should be considered protective of other postapplication inhalation exposure scenarios.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents near spraying operations. This is 

particularly the case with aerial application, but, to a lesser extent, could also be a potential 

source of exposure from the ground application method employed for fluroxypyr. The Agency 

has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead 

Agencies for pesticide regulation and other parties to develop the best spray drift management 

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

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

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 
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After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario, for which no risks of 

concern were identified, is representative of a worse case inhalation (drift) exposure and may be 

considered protective of most outdoor agricultural and commercial post-application inhalation 

exposure scenarios.

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. In the case of fluroxypyr, acute and chronic aggregate risks result from 

exposure through food and water only. For short-term risks, residential handlers’ inhalation 

exposure and children’s incidental oral exposures were combined with background exposure 

from food and water. 

7.1 Acute Aggregate Risk

Acute aggregate risk is equivalent to acute dietary exposure and risk, which is not of concern. 

Refer to Section 5.4.3.

7.2 Short-Term Aggregate Risk

The residential handler exposure from applying fluroxypyr using a Backpack sprayer and

children’s postapplication oral exposure (Table 6.3) were combined with the chronic dietary 

exposure from the mostly highly exposed adult (General US population) and children’s (all 

infants <1 year old) subpopulations (Table 5.4.5), respectively, to determine aggregate exposure 

and risk as shown in Table 7.2. Despite the numerous conservative assumptions in developing 

these estimates, the MOEs are above the LOC of 100, and are not of concern.

Table 7.2. Short-Term Aggregate Risk Calculations for Fluroxypyr

Population NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult (Handler) 100 100 1 0.01473 0.026 0.04073 2500

Child

(Postapplication) 100 100 1 0.03514 0.0070 0.04210 2400
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1

The LOC is based on the standard inter- and intra- species uncertainty factors totaling 100. The FQPA Safety Factor has been 

reduced to 1X.

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

3 Residential Exposure (Adult Handler) = Inhalation Exposure (Table 6.1). Residential Exposure (Child Postapplication) = Handto-Mouth Exposure (Table 6.2).

4 Total Exposure = (Avg. Food & Water Exposure + Residential Exposure)

5 Aggregate MOE = [100/Total Exposure]

7.3 Chronic Aggregate Risk

Chronic aggregate risk is equivalent to chronic dietary exposure and risk, which is not of 

concern. Refer to Section 5.4.4.

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 fluroxypyr and any other substances and fluroxypyr does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this action, therefore, EPA has not 

assumed that fluroxypyr 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

Fluroxypyr may be applied to rice as a foliar spray via groundboom and aerial application. The 

proposed use pattern is summarized in Table 9.1. Handler exposure is expected to be short- or 

intermediate-term based on information provided on the proposed label. The personal protective 

equipment (PPE) label requirements include: long-sleeved shirt, long pants, and shoes plus 

socks. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following exposure scenarios:

Mixer/Loaders

1. Mixing/loading liquids to support groundboom applications, 

2. Mixing/loading liquids to support aerial applications,

Flaggers

3. Flagging to support aerial application,

Applicators

4. Applying sprays with groundboom equipment, and

5. Applying sprays with aerial equipment.
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9.1 Short-/Intermediate-Term Handler Risk

No chemical-specific handler exposure data were submitted in support of the proposed use, and 

therefore HED relied on the best available surrogate data to complete the occupational handler 

assessment. Sources of generic handler data, used as surrogate data in the absence of chemicalspecific data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the 

Agricultural Handler Exposure Task Force (AHETF) database, and the Outdoor Residential 

Exposure Task Force (ORETF) database. Some of these data are proprietary (e.g., AHETF data, 

MRID No. 44339801), and subject to the data protection provisions of FIFRA. The standard 

values recommended for use in predicting handler exposure that are used in this assessment, 

known as “unit exposures,” are outlined in the “Occupational Pesticide Handler Unit Exposure 

Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), 

which, along with additional information on HED policy on use of surrogate data, including 

descriptions of the various sources, can be found at 

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

The proposed product label involved in this assessment directs applicators and other handlers to 

wear long sleeved shirt and long pants, shoes plus socks, and chemical-resistant gloves. HED 

typically assesses handler exposure using “baseline” clothing assumptions, and if risks of 

concern are identified, the use of personal protective equipment (PPE) may be incorporated into 

the exposure assessment. In the case of fluroxypyr, there is no toxicity via the dermal route, and 

only inhalation exposures were assessed. No additional PPE (i.e., respirators) were needed to 

achieve MOEs above the LOC of 100.

Standard assumptions were used with respect to body weight for adult handlers (80 kg), the 

exposure duration (i.e., short- and intermediate-term), and the area treated for various types of 

application equipment and application sites. In conjunction with these standard values, HED 

used the maximum application rates from the proposed label directions. Each of the risks is 

presented as an MOE, or the ratio of the NOAEL to the calculated daily dose.

Table 9.1 shows the results of HED’s exposure and risk assessment for occupational handlers. 

The MOEs shown in the table are all significantly higher than HED’s LOC of an MOE of 100, 

with the lowest MOE of 90,000 identified for handlers conducting mixing/loading activities for 

aerial application. Risk associated with this and all other scenarios is not of concern.

Table 9.1. Baseline Short- and Intermediate-Term Occupational Exposures and Risk Estimates for Fluroxypyr Use on Rice.

Exposure Scenario Application 

Ratea

Area 

Treated 

Dailyb

ST/IT

Baseline 

Inhalation 

UEsc

ST/IT

Baseline 

Inhalation 

Dosed

ST/IT

Baseline 

Inhalation 

MOEe

lb ai/A acres μg/lb ai mg/kg/day

Mixer/Loader

Mixing/Loading Liquids for Groundboom Application 0.34 200 0.219 0.00019 540,000

Mixing/Loading Liquids for Aerial Application 0.34 1200 0.219 0.0011 90,000

Flagger

Flagging for Aerial Application 0.34 350 0.35 0.000520 190,000
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Applicator

Applying Sprays via Groundboom Equipment 0.34 200 0.34 0.000289 350,000

Applying Sprays via Aerial Equipment 0.34 1200 0.068 0.000346 290,000

a Application Rates based on proposed uses for fluroxypyr (GF-2764 Herbicide, EPA Reg. No. 62719-577).

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c UEs = Unit Exposures based on PHED Version 1.1, ORETF, or AHETF data. Baseline = no gloves, no respirator.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled/day (acres/day) x conversion 

factor (1 mg/1,000 μg) × absorption factor (%) ÷ body weight (80 kg). No inhalation absorption factor.

e MOE = NOAEL ÷ Dose (mg/kg/day). ST/IT Inhalation NOAEL = 100 mg/kg/day. ST/IT level of concern = 100. 

9.2 Short and Intermediate -Term Postapplication Risk

9.2.1 Dermal Postapplication Risk

Agricultural workers performing typical post-application activities (e.g. scouting, hand weeding)

may receive exposure to fluroxypyr residues. As no dermal endpoint has been identified, no 

quantitative dermal postapplication assessment is necessary. 

Typically, under WPS for Agricultural Pesticides, active ingredients classified as acute Toxicity 

Category III or IV for Acute Dermal, Eye Irritation, and Primary Skin Irritation are assigned a 

12-hour REI. Based on the quantitative post-application assessment, the 12-hour REI on the 

proposed label is acceptable for rice.

9.2.2 Inhalation Postapplication Risk

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for fluroxypyr at this time primarily because it has a low vapor 

pressure (9.7 x 10-7 mm Hg), it is applied at an application rate of 0.34 lbs ai/A, and it is not 

projected to be applied via typically high inhalation exposure application equipment (e.g., 

airblast). However, volatilization of pesticides may be a potential source of postapplication 

inhalation exposure to individuals nearby to 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. The 

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

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

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate postapplication inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative postapplication inhalation exposure assessment 

for fluroxypyr.

Although a quantitative occupational postapplication inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than postapplication exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of occupational postapplication inhalation 

exposure scenarios.
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10.0 References

Residue Chemistry

Fluroxypyr, Section 3 Registration of Fluroxypyr on Rice, Summary of Analytical Chemistry 

and Residue Data. 

Fluroxypyr: Chronic Dietary (Food and Drinking Water) Exposure and Risk 

Assessment for the Section 3 Registration Action to Support New Use on Rice, and for all the

Commodities of Crop Group 15 (Cereal Grains).

Occupational and Residential Exposure 

Fluroxypyr: Occupational Exposure Assessment for a Proposed New Use on Rice with an 

Updated Residential Exposure Assessment of All Existing Residential Uses (Turf). Matthew 

Lloyd, D402132, 09/11/2012.
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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Available for Fluroxypyr

The toxicological data requirements (40 CFR 158.340) for food uses for fluroxypyr are in 

Table A1. Use of the new guideline numbers does not imply that the new (1998) guideline 

protocols were used.

Table A.1 Test 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 (rat and mouse) ...................................

870.3150 Oral Subchronic (dog)....................................................

870.3200 21/28-Day Dermal (rat)..................................................

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

870.3465 28-Day Inhalation ..........................................................

yes

yes

yes

CR

noA

yes

yes

yes

no

no

870.3700a Developmental Toxicity (rat).........................................

870.3700b Developmental Toxicity (rabbit)....................................

870.3800 Reproduction (rat)..........................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rat) ....................................................

870.4100b Chronic Toxicity (dog)...................................................

870.4200a Carcinogenicity (rat) ......................................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Chronic/Carcinogenicity (rat) ........................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial .....................

870.5300 Mutagenicity—Gene Mutation - mammalian ................

870.5375 Mutagenicity—Structural Chromosomal Aberrations ...

870.5395 Mutagenicity—Mammalian Erythrocyte Micronucleus.

870.5500 Mutagenicity— Bacterial DNA Damage or Repair Test

870.5550 Mutagenicity—Unscheduled DNA Synthesis.................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

no

no

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 (rat) ................................

no

no

yesA

yesA

CR

---

---

NA

NA

NA

870.7485 General Metabolism (rat)...............................................

870.7600 Dermal Penetration (8-hour), in vivo (male rat).............

yes

CR

yes

yes

870.7800 Immunotoxicity (rat)........................... Yes Yes

A waived (HASPOC TXR No. 0056397)
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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity of Fluroxypyr Acid and Fluroxypyr 1-Methylheptyl Ester (MHE) Technical

Guideline No. Study Type MRIDs # Results

Toxicity 

Category

870.1100 Acute Oral - rat Acid 40354010 LD50 = 2405 mg/kg III

MHE 40354005 LD50 > 5000 mg/kg IV

870.1200 Acute Dermal – rabbit 

- rat

Acid 40354010 LD50 > 5000 mg/kg III

MHE 40354006 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation Acid 40354011 LD50 > 296 mg/m3

II

MHE 40354004 LD50 > 1.0 gm/m3III

870.2400 Primary Eye Irritation -

rabbit

Acid 49354010 not applicable not applicable

MHE 40354007 mildly irritating III

870.2500 Primary Skin Irritationrabbit

Acid 40354010 non-irritating IV

MHE 40354008 non-irritating IV

870.2600 Dermal Sensitization -

guinea pig

Acid - none not applicable not applicable

MHE 42137335 & 

42540900

not a sensitizer not applicable

Attachment 2. Toxicity Profile for Fluroxypyr

Table A2. Toxicity Profile of Fluroxypyr Technical (Fluroxypyr acid and Fluroxypyr MHE)

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3150

28-day oral toxicity

Dog

MRID 42137340 (1983)/ 

acceptable/

fluroxypyr acid 98% a.i.

0, 20, 50, 150 mg/kg/day in diet

NOAEL = 50 mg/kg/day 

LOAEL= 150 mg/kg/day, based on kidney lesions (early 

signs of acute tubular nephrosis), increased adrenal wts (both 

sexes), decreased testes wts (males)

870.3100

90-Day oral toxicity 

rodents (rats)-Fischer 344

MRID 44080316(1991)/ 

acceptable/ 

fluroxypyr acid 98.9% a.i.

0, 320, 700, 1000 mg/kg/day

NOAEL = 700 mg/kg/day

LOAEL = 1000 mg/kg/day, based on decreased body weight 

gain & testis weight (males), decreased brain weight 

(females), and increased kidney weight (both sexes). There 

were no treatment-related microscopic lesions.

870.3100

90-Day oral toxicity 

rodents (rats)--Wistar

MRID 42164502 (1987)/ 

acceptable/ 

fluroxypyr acid 98.3-98.5% a.i.

0, 80, 750, 1000, 1500 

mg/kg/day

Mean intake: M 79, 721, 924, 

1215; F 81, 755, 969, 1392 mkd

Males

NOAEL = 80 mg/kg/day

LOAEL = 750 mg/kg/day, based on nephrotoxicity and death 

Females

NOAEL = 750 mg/kg/day 

LOAEL = 1000 mg/kg/day, based on nephrotoxicity and 

death 
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Table A2. Toxicity Profile of Fluroxypyr Technical (Fluroxypyr acid and Fluroxypyr MHE)

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day oral toxicity 

rodents (mice) – SPF ICR

MRID 42137337(1988)/ 

acceptable/ 

fluroxypyr acid 99.3% a.i.

0, 200, 500, 2500, 10000 ppm

Male: 0, 27, 67, 336, 1342 

mg/kg/day

Female: 0, 35, 87, 437, 1748 

mg/kg/day

NOAEL = 1342 mg/kg/day (males)/1748 mg/kg/day 

(females)

LOAEL not established.

870.3150

90-Day oral toxicity 

(nonrodents)

NA NA

870.3200

21-Day dermal toxicity

(rabbits)

MRID 42137338(1991)/ 

acceptable/

fluroxypyr MHE 98.5% a.i.

0, 100, 300, 1000 mg/kg/day

NOAEL = 1000 mg/kg/day (HDT)

LOAEL not established.

870.3250

90-Day dermal toxicity

NA NA

870.3465

4-Week inhalation toxicity

(rat)

NA NA

870.3700a

Prenatal developmental 

toxicity (rats) - CD

MRID 40244509 (1983) 

acceptable/ 

fluroxypyr acid 99% a.i.

GD 6-19

0, 125, 250, 500 mg/kg/day

Maternal NOAEL = 250 mg/kg/day

LOAEL = 500 mg/kg/day, based on increased kidney weights

(one death).

Developmental NOAEL = 500 mg/kg/day (HDT)

LOAEL not established.

870.3700a

Prenatal developmental 

toxicity (rats) –SpragueDawley

MRID 44094901 (1994) 

acceptable/ 

fluroxypyr MHE 95.8% a.i.

GD 6-15

0, 100, 300, 600 mg/kg/day

Maternal NOAEL = 300 mg/kg/day

LOAEL = 600 mg/kg/day, based on increased maternal 

deaths (days 4, 6, 7, 7, 8, 8, 10, 10) and decreased body 

weight gains and food consumption.

Developmental NOAEL = 600 mg/kg/day (HDT)

LOAEL = not established.

870.3700b

Prenatal developmental 

toxicity (rabbits)

MRID 40354013 (1984) 

acceptable/ 

fluroxypyr acid 95.8% a.i.

0, 25, 100, 250, 400 mg/kg/day

GD 6-19

Maternal NOAEL = 250 mg/kg/day

LOAEL = 400 mg/kg/day, based on increased maternal 

deaths. Due to a large number of maternal deaths in this

group, a dose level of 250 mg/kg/day was added to the study, 

and the 400 mg/kg/day dose level was discontinued early

(terminated on day 9).

Developmental NOAEL = 250 mg/kg/day (HDT)

LOAEL not established.
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Table A2. Toxicity Profile of Fluroxypyr Technical (Fluroxypyr acid and Fluroxypyr MHE)

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3700b

Prenatal developmental 

toxicity (rabbits)

MRID 44080319 (1996) 

acceptable/ 

fluroxypyr MHE 95.8% a.i.

0, 100, 500, 1000 mg/kg/day

GD 7-19

(acid equivalent doses: 69, 346, 

or 693 mg/kg/day)

Maternal NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on increased abortions

(one doe on GD 25). At 1000 mg/kg/day, 3 does aborted (GD 

22, GD 25, GD 25) and 1 death GD 20.

Developmental NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on increased abortions

(one doe on GD 25). At 1000 mg/kg/day, 3 does aborted (GD 

22, GD 25, GD 25) and 1 death GD 20.

870.3800

Reproduction and fertility 

effects (rats) – SpragueDawley

MRID 44080321 (1996) 

acceptable/ 

fluroxypyr acid 99% a.i.

0, 100, 500, 750 mg/kg/day (M)

0, 100, 500, 1000 mg/kg/day (F)

Parental/Systemic NOAEL = 100 mg/kg/day (males) /500 

mg/kg/day (females)

LOAEL = 500 mg/kg/day (males)/ 1000 mg/kg/day 

(females), based on kidney effects (both sexes; increased 

kidney weight with microscopic findings) and increased 

deaths (females) due to renal failure.

Reproductive NOAEL = 750 mg/kg/day (Males)/1000 

mg/kg/day (females) (HDT)

LOAEL not established.

Offspring NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on decreased pup weight 

and body weight gain and slightly lower survival.

870.4100a

Chronic toxicity (rodents)

NA; see 870.4300 NA

870.4100b

Chronic toxicity (dogs)

MRID 40244507(1988)

acceptable/ 

fluroxypyr acid 98%a.i.

0, 20, 50, 150 mg/kg/day

NOAEL = 150 mg/kg/day (HDT)

LOAEL not established.

870.4200a

Carcinogenicity (rats)

NA; see 870.4300 NA

870.4200b

Carcinogenicity (mice)-

CD-1

MRID 44080317 (1991) 

acceptable/guideline

fluroxypyr acid 98.9% a.i.

0, 100, 300, 1000 mg/kg/day

NOAEL = 300 mg/kg/day 

LOAEL = 1000 mg/kg/day, based on decreased body weight 

and body weight gain (males) and increased kidney lesions 

(increased incidences of renal papillary necrosis and 

regenerative nephrosis) in females.

No evidence of carcinogenicity.

870.4300

Combined 

Chronic/carcinogenicity 

(rats)—Fischer 344

MRID 44080322 (1994) 

acceptable/guideline

fluroxypyr acid 99% a.i.

0, 100, 500, 1000 mg/kg/day

NOAEL =100 mg/kg/day

LOAEL = 500 mg/kg/day, based on increased kidney weights 

and chronic progressive kidney glomerulonephropathy (both 

sexes).

No evidence of carcinogenicity.

At 1000 mg/kg/day, 5 male rats died within first 90 days on 

test.
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Table A2. Toxicity Profile of Fluroxypyr Technical (Fluroxypyr acid and Fluroxypyr MHE)

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.5100

Bacterial reverse mutation

MRID 44080323 (1995) 

acceptable/ 

fluroxypyr MHE 95.8% a.i.

100 - 5000 ug/plate

Negative.

870.5300

In vitro mammalian cell 

gene mutation

MRID 44080324 (1996) 

unacceptable/

fluroxypyr MHE 95.8% a.i.

1.25 - 50 ug/mL

Negative, but did not test a soluble dose.

870.5375

In vitro mammalian 

chromosome aberration 

(HL)

MRID 44080325 (1996) 

acceptable/ 

fluroxypyr MHE 95.8% a.i.

0.42 – 1250 ug/mL

Negative.

870.5395

Mammalian micronucleus 

(mouse)

MRID 44080326 (1996) 

acceptable/ 

fluroxypyr MHE 95.8% a.i.

oral gavage of 225, 450 or 900 

mg/kg

Negative.

870.6200a

Acute neurotoxicity 

screening battery

(rats)

NA NA

870.6200b

Subchronic neurotoxicity 

screening battery

(rats)

NA NA

870.6300

Developmental 

neurotoxicity

(rats)

NA NA
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870.7485

Metabolism

(Fischer 344 rats)

MRID 44080327 (1996) 

acceptable/ 

fluroxypyr MHE 99% a.i.

Males: 50 mg/kg (labeled) as 

single oral dose

Total recovery of the administered dose was 105%, with the 

principal route of excretion being expired 14CO2, which 

contained approximately 61% of the radioactivity for the 

fluroxypyr MHE. The urine contained approximately 30% 

and the feces contained 5% of the administered dose. At 48 

hours post dose, approximately 7% of the administered dose 

was recovered in the blood, carcass, and skin. Approximately 

52% of the administered dose was absorbed and expired as 

14CO2 within 12 hours post dose, and an additional 18% of 

the administered dose was excreted in the urine within 12 

hours post dose. Based on the percentage of dose in the 

expired 14CO2, urine, and tissues, approximately 90% of the 

dose was absorbed. Once absorbed, it was extensively 

metabolized and rapidly expired as 14CO2 and eliminated in 

the urine with a half-life of 6 hours. Peak plasma 

concentrations of 14C-radioactivity were attained by 7 hours 

post dose.

870.7600

Dermal penetration

NA NA

870.7800

Immunotoxicity (Crl:WI 

(Han) rats)

MRID 48581311 (2011)

Acceptable/guideline

fluroxypyr 99.9%

Males: 0, 80, 250, 750 

mg/kg/day for 29 days

NOAEL = 750 mg/kg/day (highest dose tested; actual dose 

was 816 mg/kg/day); no treatment-related decrease in primary 

immune response to SRBCs in male rats; spleen or thymus 

weights comparable to control.
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Appendix B. 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 Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; and the Outdoor Residential Exposure Task Force 

(ORETF) database; are subject to ethics review pursuant to 40 CFR 26, have received that 

review, and are compliant with applicable ethics requirements. For certain studies that 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 http://www.epa.gov/pesticides/science/handlerexposure-data.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.