Flurprimidol Human Health Draft Risk Assessment DP No. D427106 

UNITED STATES ENVIRONMENTAL PROTECTIO AGENCY 

W J\S HfNGTON. D.C. 20460 

MEMORANDUM 

Date: June 4, 2015 

OFFICE OF 

CllE\llC \I. S.-\FET\ .\:'\O 

POI.LI TIO:'\ PIU t;:;\ 1'10'1 

SUBJECT: Flurprimidol: Human Health Draft Risk Assessment for Registration Review. 

PC Code: 12570 I 

Decision No.: 503929 

Petition No.: NIJ\ 

Risk Assessment Type: Single 

Chemical/ Aggregate 

TXR No.: NIA 

MRID No.: NI A 

DP Barcode: 427106 

Registration No.: NIA 

Regulatory Action: Registration Review 

Case No.: N/ A 

CAS No.: 56425-91 -3 ' 

40 CFR: NIA 

FROM: Chris 

Monica 

Schlosser, 

Hawkins, 

Ri

Ph

sk 

.D.

Assessor, 

, .P.H.

Toxic

, Pl:lvironmenta

ologist ~~l Hea lth ~,?,;' Scientist ~ ~ ~ Sheila Piper, Chemist 6 ~~ ~,._,,; 

Risk Assessment Branch Vf 

THROUGH: 

Ri

Don

sk 

n

Assessment 

a Davis, Act

Branch 

ing Bran

VI 

ch hief~l.C'c_.J a~ 

Health Effects Division 

TO: Kelly Ballard, Chemical Review Manager 

Neil Anderson, Branch Chief 

Risk Management and J mplementation Branch I 

Pesticide Re-evaluation Division (7508P) 

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human hea lth from exposure to pesticides. As part of Registration Review, 

the Pesticide Re-evaluation Division (PRO) of OPP has requested that HED evaluate the hazard 

and exposure data and conduct di etary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the registered 

uses of flurprimidol. 

HED has evaluated the toxicity and exposure databases for the active ingredient, flurprimidol, 

and has conducted a human health risk assessment in support of Registration Review. 

Page 1 of 48 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106 

A summary of the findings and an assessment of human health risk resulting from the currently 

registered uses of flurprimidol are provided in this document. The HED team members 

contributing to this risk assessment include Chris Schlosser (risk and hazard assessment), 

Monica Hawkins (occupational and residential assessment), and Sheila Piper (dietary 

assessment). James Wolf of the Environmental Fate and Effects Di vision (EFED) performed the 

drinking water assessment. 

Page 2 of 48 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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1.0 Executive Summary ...........................................................................................................5

2.0 HED Recommendations ....................................................................................................6

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

2.2 Tolerance Considerations and International Harmonization........................................7

2.3 Label Recommendations...................................................................................................7

2.3.1 Recommendations from Occupational/Residential Assessment..............................7

3.0 Ingredient Profile...............................................................................................................7

3.1 Chemical Identity...............................................................................................................7

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

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

3.4 Anticipated Exposure Pathways.....................................................................................10

3.5 Consideration of Environmental Justice .......................................................................10

4.0 Hazard Characterization and Dose-Response Assessment..........................................11

4.1 Toxicology Studies Available for Analysis.....................................................................11

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME).................................11

4.2.1 Dermal Penetration....................................................................................................12

4.3 Toxicological Effects........................................................................................................12

4.4 Safety Factor for Infants and Children .........................................................................13

4.4.1 Completeness of the Toxicology Database...............................................................13

4.4.2 Evidence of Neurotoxicity .........................................................................................13

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .........14

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

4.5.1 Dose-Response Assessment .......................................................................................14

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment......16

4.5.3 Cancer Classification and Risk Assessment Recommendation .............................16

4.5.4 Summary of Points of Departure and Toxicity Endpoints ....................................17

4.6 Endocrine Disruption ......................................................................................................18

5.0 Dietary Exposure and Risk Assessment.........................................................................19

5.1 Food Residue Profile........................................................................................................19

5.2 Summary of Environmental Degradation .....................................................................19

5.3 Water Residue Profile......................................................................................................19

5.4 Dietary Risk Assessment .................................................................................................20

5.4.1. Description of Residue Data Used in Dietary Assessment .....................................20

5.4.2 Percent Crop Treated Used in Dietary Assessment................................................20

5.4.3 Acute Dietary Risk Assessment ................................................................................20

5.4.4 Chronic Dietary Risk Assessment ............................................................................21

5.4.5 Cancer Dietary Risk Assessment..............................................................................21

5.4.6 Dietary Summary Table ............................................................................................21

6.0 Residential Exposure and Risk Estimates .....................................................................22

6.1 Residential Handler Exposure/Risk Estimates .............................................................22

6.2 Residential Post-application Exposure/Risk Estimates................................................24

6.3 Spray Drift........................................................................................................................25

6.3.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications ..............26

6.4 Residential Bystander Post-Application Inhalation Exposure ....................................26

7.0 Combined Exposure/Risk Characterization..................................................................27

8.0 Cumulative Exposure/Risk Characterization ...............................................................27
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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9.0 Occupational Exposure and Risk Estimates..................................................................27

9.1 Occupational Handler Exposure/Risk Estimates..........................................................27

9.2 Occupational Post-application Exposure/Risk Estimates............................................35

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates ...................35

Appendix A. Toxicology Profile and Executive Summaries ...................................................37

A.1 Toxicology Data Requirements.......................................................................................37

A.2 Toxicity Profiles ...............................................................................................................38

A.3 Hazard Identification and Endpoint Selection..............................................................43

Appendix B. DEEM-FCID Model Inputs and Outputs for Acute and Chronic Dietary 

Exposure Estimates..........................................................................................................46
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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1.0 Executive Summary

Flurprimidol is a turf grass and woody-plant growth regulator that belongs to the pyrimidine 

class of chemicals and has multiple end-use products that are registered for use on perennial 

turfgrass (cool and warm season) on golf courses and turf, landscape/woody ornamental plants, 

ornamental trees, and ornamental plants grown in containers in nurseries, greenhouses, and 

shadehouses. Most of the flurprimidol product labels direct mixers, loaders, applicators, and 

other handlers to wear long-sleeved shirt, long pants, shoes and socks, and chemical-resistant 

gloves. Flurprimidol is marketed as a wettable powder in water-soluble packets, liquid 

concentrate, granule, and soluble concentrate. There are currently no registered food uses for

flurprimidol. 

The toxicology database for flurprimidol is complete and provides sufficient information to 

adequately identify hazards for risk assessment purposes. In mammals, flurprimidol targets the 

adrenal gland in dogs and the liver in rats. There are no concerns for neurotoxicity or 

susceptibility to the young. Based on the available data, no evidence of genotoxic, or 

immunotoxic effects were identified in the database. In the 2005 Human Health Risk 

Assessment, flurprimidol was classified “not likely to be carcinogenic to humans.” 

For acute dietary assessment of the general population, the acute neurotoxicity study in rats was 

selected with a NOAEL of 70 mg/kg/ based on treatment related findings at the mid-dose (285 

mg/kg), including gait abnormality in both sexes, low arousal and impaired righting reflex in 

males, and hunched body in females, 7-8 hours after dosing. For females 13 – 49 years old, the 

developmental toxicity study in rats was selected with a NOAEL of 10 mg/kg/day for dams and 

pups. Skeletal abnormalities seen at the study LOAEL of 45 mg/kg/day could be from a single 

exposure during pregnancy and are, therefore, considered a potential acute effect, and 

appropriate for the acute dietary endpoint scenario for females of child-bearing age. For chronic 

dietary exposure and risk assessment, the chronic toxicity study in rats was selected with a 

NOAEL of 3.6 mg/kg/day. The LOAEL is 12.1 mg/kg/day based on increased incidences of 

focal atypia, fatty change, and hepatocellular eosinophilic change in the liver of males. A dermal 

assessment is not required for flurprimidol since this chemical does not pose a dermal hazard. 

For short and intermediate-term inhalation exposure, the 13-week inhalation toxicity study in rats 

was selected with a NOAEL of 0.1 mg/L based on nasal hyperplasia observed at the next highest 

dose (0.4 mg/L). A human equivalent concentration (HEC) was calculated from the inhalation 

study. For inhalation exposure, the standard interspecies extrapolation uncertainty factor can be 

reduced from 10X to 3X due to the HEC calculation accounting for pharmacokinetic (not 

pharmacodynamic) interspecies differences. The intraspecies uncertainty factor remains at 10X. 

For all other routes of exposure a 100X uncertainty factor is applied (interspecies factor of 10X 

and intraspecies factor of 10X). 

 

Food Quality Protection Act (FQPA) considerations do not apply to flurprimidol since currently 

registered use patterns are all non-food uses. While there are potential exposures to infants and 

children from turf use patterns of flurprimidol, there are adequate pre- and/or postnatal toxicity 

studies that demonstrate no residual uncertainties to infants and children for pre- and/or postnatal 

susceptibilities. These studies have clearly defined NOAEL/LOAELs and the selected points of 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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departure (PODs) are protective of all observed adverse effects, including clinical signs 

indicative of neurotoxicity that were observed in the ACN. 

Flurprimidol is mobile and resistant to degradation in the soil and stable to hydrolysis suggesting 

the potential for leaching and movement to roots for uptake in water by growing plants. Based 

on the environmental fate parameters, there is the potential for flurprimidol to reach drinking 

water resources. The Environmental Fate and Effects Division (EFED) performed Tier 2 surface 

water and groundwater modeling using the highest application rates. The highest estimated 

drinking water concentrations were from groundwater. 

No exposure from food is expected. A dietary assessment was conducted for drinking water 

only. The acute drinking water risk estimates are below HED’s level of concern (<100% of the 

acute population adjusted dose (aPAD)) for the general U.S. population and all population 

subgroups; the population subgroup with the highest risk estimate is females 13 to 49 years old 

which utilize 38% of the aPAD. The resulting drinking water chronic exposure estimates were 

less than HED’s level of concern (<100% cPAD) for the general U.S. population and all 

population subgroups; the most highly exposed population subgroup was all infants (<1 years 

old) with an estimated risk of 89% of the cPAD.

Residential handler short-term exposure is anticipated from the registered uses. The residential 

handler exposure and risk estimates indicate that the inhalation margins of exposure (MOEs) are 

greater than HED’s LOC (i.e., MOEs are ≥ 30). The MOEs range from 2,000 to 1,300,000. 

Residential post-application dermal exposure for adults or children was not quantitatively 

assessed for flurprimidol because there is no identified dermal hazard. Also, residential postapplication incidental oral exposure for children was not assessed based on the registered use 

sites. Combined exposure assessments were not conducted since exposures should not be 

combined across routes of exposure for this chemical, and there is only a single source of oral 

exposure from drinking water. A quantitative spray drift assessment was conducted. Risk 

estimates from groundboom applications are not of concern from the field edge for all scenarios 

considered. 

Occupational handler short- and intermediate-term exposure is anticipated from the registered 

uses. The occupational handler exposure and risk estimates indicate that the short- and 

intermediate-term inhalation MOEs are not of concern to HED (i.e., MOEs ≥ 30) at the baseline 

attire (i.e., no gloves and no respirator). The MOEs range from 1,100 to 900,000. Occupational 

post-application dermal exposure was not quantitatively assessed since there is no dermal hazard 

for flurprimidol. 

2.0 HED Recommendations

2.1 Data Deficiencies

No toxicology, residue chemistry or occupational/residential data deficiencies were identified for 

flurprimidol. 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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2.2 Tolerance Considerations and International Harmonization

There are no food uses for flurprimidol at this time; therefore, a discussion of tolerances and 

international harmonization is not relevant to this chemical.

2.3 Label Recommendations 

2.3.1 Recommendations from Occupational/Residential Assessment

The Registration Division (RD) should ensure that the proper personal protective equipment 

(PPE) is listed on all flurprimidol labels. There are several labels that do not contain this 

information. For example, EPA Registration #67690-34 (Flurprimidol Solution) and 67690-68 

(Cutless 0.67G) do not contain any PPE information.

3.0 Ingredient Profile

3.1 Chemical Identity

Table 3.1 Compound Structure and Nomenclature

Chemical Structure

Empirical Formula C15H15F3N202

Common name Flurprimidol

Company experimental 

name

N/A

IUPAC name alpha-(1-methylethyl)-alpha-[4-(trifluoromethyoxy) phenyl]-5-

pyrimidinemethanol 

CAS name alpha-(1-methylethyl)-alpha-[4-(trifluoromethyoxy) phenyl]-5-

pyrimidinemethanol 

CAS Registry Number 056425-91-3

End-use product/EP Topflor

Chemical Class pyrimidine plant growth regulator

Known Impurities of 

Concern

N/A
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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3.2 Physical/Chemical Characteristics

Flurprimidol is a white to pale yellow crystalline solid under normal temperature and mostly 

odorless. Flurprimidol is not expected to be volatile, has a moderate solubility in water, and a 

low potential to bioaccumulate as demonstrated by its relatively low Kow. Flurprimidol is 

resistant to degradation (e.g., half-life > 400 days) in the soil and stable to hydrolysis.

Table 3.2. Physical and Chemical Properties of Flurprimidol

Parameter Value Reference

Molecular Weight 312.3 US EPA Pesticide Fact 

Melting point/range 93-95C Sheet 1989

pH 6.5-8.9 in D-H20

Density 0.83 to 0.88g/cc

Water solubility (20 C) 120-140 ppm

Vapor pressure (25 C) 3.64 x 10-7 mmHg

Octanol/water partition coefficient, 

logPOW (25 C)

Kw = 9.33

3.3 Pesticide Use Pattern

Flurprimidol has multiple end-use products that are registered for use on perennial turfgrass 

(cool and warm season) on golf courses and turf, landscape/woody ornamental plants, 

ornamental trees and ornamental plants grown in containers in nurseries, greenhouses, and 

shadehouses. Flurprimidol is marketed as a wettable powder in water-soluble packets, liquid 

concentrate, granule, and soluble concentrate. For most use sites, baseline attire (i.e., longsleeved shirt, long pants, shoes, and socks) and chemical-resistant gloves are required.

Table 3.3 provides a summary of the highest application rate of the registered uses for 

flurprimidol. 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Table 3.3. Summary of Registered Uses for Flurprimidol

Crop/Use Site Type of 

Application

Register

ed 

Formula

tions

Maximum 

Application 

Rate

PPE Use Directions and 

Limitations

Turf

Golf Course 

Turf

broadcast 

treatment for 

golf courses, 

backpack 

sprayer for 

edging/bandi

ng, hand-held 

equipment

WP in 

WaterSoluble 

Packets

1.5 lb ai/A

(Edging/Ban

ding)

(0.008 lb 

ai/gallon,

0.000034 lb 

ai/ft2);

0.75 lb ai/A

(Fairways)

0.25 lb ai/A

(Greens, Tees 

Only)

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves

Do not apply through any type 

of irrigation system. Can be 

applied to turfgrass in edging 

and banding applications along 

the perimeter of lawns, 

landscape beds, sidewalks, 

curbs, parking lots, driveways, 

posts, mailboxes, building 

structures, gravestones, and 

fences.

Landscape 

ornamentals,

Woody 

ornamental 

shrubs and 

hedges1

Rotary-type, 

gravity-fed, 

airflow 

driven 

spreader

G

1.5 ai/A 

(0.000034 lb 

ai/ft2) for 

landscape 

ornamentals

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves

Do not apply to annual bedding 

plants.

Golf Course 

Turf

Drop, rotarytype spreader G

1.0 lb ai/A 

for fairways, 

0.75 lb ai/A 

for greens, 

tees

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves, 

protective 

eyewear

Do not apply this product to be 

inadvertently applied to non-turf 

areas such as flowerbeds or 

ornamental shrubs as growth 

inhibition may occur.

Ornamental 

Plants Grown 

in Commercial 

Nurseries, 

Greenhouses, 

Shadehouses

Spray, 

Drench/Soil/

GroundDirected, 

Chemigation

Foliar 

Spray

0.55 lb ai/A

(.00165 lb 

ai/gallon, 

0.00001275 

lb ai/ft2)

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves, 

coveralls

For commercial use. In New 

York the product can be used for 

greenhouse applications only. 

Do not apply through any type 

of chemigation in California or 

New York.

Landscape 

Ornamentals 

(Shrubs, 

Bushes)

Hand-held

WP in 

WaterSoluble 

Packets

1.08 lb ai/A

(0.000024 lb 

ai/square 

feet; 0.005 lb 

ai/gallon)

SL w/CR 

gloves, 

coveralls, and 

protective 

eyewear 

(goggles or 

face shield)

Do not apply through any type 

of chemigation. Do not apply to 

annual bedding plants. Do not 

use for treatment of trees. Do 

not use on plants from which 

fruits, nuts or other commodities 

may be produced for human 

consumption or livestock feed.

Landscape 

Ornamentals,

Hand-held 

for containerG 1.5 lb ai/A Long-sleeved shirt, long 

For perennial landscape 

ornamentals the label states the 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Table 3.3. Summary of Registered Uses for Flurprimidol

Crop/Use Site Type of 

Application

Register

ed 

Formula

tions

Maximum 

Application 

Rate

PPE Use Directions and 

Limitations

ContainerGrown 

Ornamentals, 

Woody 

Ornamental 

Shrubs,

Plants, Flowers

grown 

ornamentals,

push type 

spreader, 

belly grinder 

spreader

pants, shoes, 

socks, 

chemicalresistant 

gloves

product is not for use by 

homeowners. Do not apply to 

annual bedding plants or areas 

intended for annual bedding 

plants within 6 months of 

application of Cutless 0.33G. 

The product is not suitable for 

treatment of ornamental trees.

Turf

Hand-held, 

push type 

spreader

G 1.5 lb ai/A

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves

Apply the product along the 

perimeter of lawns, landscape 

beds, sidewalks, curbs, 

driveways, fences, mailboxes, 

building structures, and light 

posts.

Ornamental 

Trees Injection

Readyto-Use

Liquid

1.46 lb ai/day NS Do not inject food bearing trees.

Ornamental 

Trees Implant

Readyto-Use

Liquid

1.5 g/tree

Long-sleeved 

shirt, long 

pants, shoes, 

socks, 

chemicalresistant 

gloves

For a 30-inch diameter tree 

apply 45 implants which is

equivalent to 1.5 g/tree.

 NS = Not Specified; G = granular.

1 Note: This product is an impregnated fertilizer that could be applied by a tractor-drawn spreader. Therefore, the assessment addresses 

occupational handler exposure from the tractor-drawn spreader.

3.4 Anticipated Exposure Pathways

Humans may be exposed to flurprimidol in drinking water, as the registered uses may result in 

flurprimidol reaching ground water. In a residential setting, adults applying the pesticide may be 

exposed, however, application is limited to the edges of turf; therefore significant exposure to 

adults and children resulting from contact with treated turf is not anticipated. Workers may be 

exposed occupationally during the mixing, loading, and apply of the pesticide. 

3.5 Consideration of Environmental Justice

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

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

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

(http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) 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 and ethnic group. 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 post-application 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

4.1 Toxicology Studies Available for Analysis

The toxicology database for flurprimidol is complete and provides sufficient information to 

adequately identify hazards for risk assessment purposes. Since the last risk assessment acute and 

subchronic neurotoxicity, immunotoxicity, and subchronic inhalation studies have been 

submitted to the Agency and incorporated into this assessment. The database includes the 

following studies:

 90-Day oral toxicity studies in the rat, mouse and dog,

 21-Day dermal toxicity in the rabbit,

 90-Day inhalation toxicity in the rat, 

 Developmental toxicity in the rat and rabbit,

 2-Generation reproductive toxicity in the rat,

 Chronic toxicity in the rat and dog,

 Carcinogenicity in rat and mouse,

 Genetic toxicity battery,

 Acute and subchronic neurotoxicity in the rat,

 Metabolism study in the rat, and 

 Immunotoxicity study in the rat. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Flurprimidol is rapidly (peak plasma levels occur at 5-10 hours after dose in both sexes) and 

highly (84-99%) absorbed following a single oral dose at low and high doses (2.5 and 50 

mg/kg/day). 

Following a single dose, tissue distribution studies demonstrated no significant accumulation 48 

hours after dosing in the low or high dose groups. However, minor accumulation was observed 

in the liver (0.7%). Following multiple doses (low dose only), no significant tissue accumulation 
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(0.1% in the liver) was observed. Based on the available information, no evidence of 

bioaccumulation was identified. 

Flurprimidol was extensively metabolized into over 30 metabolites with less than 2.5% of the 

unchanged parent being identified in the feces. The primary metabolite was identified (βhydroxy-α-methyl-β-[4-(trifluoro-methoxy)phenyl]-5-pyrimidinepropanoic acid) and was present 

at 10-20% dose, mainly in the urine. Other metabolites individually accounted for less than 6% 

of the dose. Major metabolic pathways include oxidation of the isopropyl group and the 

pyrimidine ring. Oxidation of the carbinol-carbon atom and dehydration between the carbinolcarbon atom and isopropyl group were also observed. 

The majority of the dose was excreted within 2 days (90-96% at the low dose and 78-80% at the 

high-dose). The elimination half-life was reported as 31 to 42 hours. At the low dose, excretion 

occurred primarily in the urine (61 to 74%) with the remaining dose being excreted in the feces 

(25 to 34%). At high doses, lower amounts were excreted in the urine (52-59%) indicating a 

saturation of the absorption processes. Biliary excretion studies in rats indicated most of the 

radioactivity eliminated in the feces was absorbed from the gastrointestinal tract and eliminated 

through the bile.

No significant sex-dependent pharmacokinetic differences were identified at either low- or highdoses.

4.2.1 Dermal Penetration

A dermal penetration study was conducted in rhesus monkeys but was unacceptable for risk 

assessment purposes. However, using a NOAEL/LOAEL extrapolation, the upper bound limit 

for dermal absorption can be estimated as 6% based on comparison of the 60 mg/kg/day LOAEL 

in rabbits from the developmental study for decreased body weight gain and the 1,000 mg/kg/day 

NOAEL in rabbits from the dermal toxicity study. 

4.3 Toxicological Effects

Flurprimidol is a turf grass and woody-plant growth regulator that belongs to the pyrimidine 

class of chemicals. Its pesticidal mode of action is to inhibit the early stages of gibberellin 

biosynthesis. The mammalian mode of action has not been elucidated. In mammals, flurprimidol 

targets the adrenal gland in dogs and the liver in rats. No adverse effects were observed 

throughout the database in the mouse. In rats, liver effects were only observed following chronic 

exposure and were evidenced by increased liver weights and histopathological changes including 

focal atypia, fatty change, and eosinophilic change in both sexes. Adrenal effects in dogs 

included decreased plasma cortisol levels and adrenal gland weights, adrenal cortical 

vacuolation, slight cortical atrophy, and eosinophilic change in both sexes. The effects were 

observed at similar doses following both 14-day, sub-chronic, and chronic exposure and did not 

show progression of toxicity over time. The lack of progression over time is further supported by 

the metabolism data indicating that flurprimidol does not bioaccumulate in tissues. 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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In the 2-generation reproductive toxicity study no qualitative or quantitative susceptibility was 

observed. Reproductive effects included decreased fertility and fetal survival. In the offspring, 

effects included decreased survival and body weights observed in the presence of overt maternal 

toxicity. In the developmental studies, qualitative susceptibility was seen in the rat offspring, 

based on an increased incidence of microphthalmia, a developmental disorder of the eye where 

one or both of the eyes are abnormally small, and skeletal anomalies in the vertebrae (extra) and 

ribs (extra, rudimentary, cervical). These effects were observed in the presence of significantly 

decreased body weights gains (up to 138%) in maternal animals on gestation days 6-10. In the 

rabbit developmental study, anorexia, increased abortions, weight loss, and decreased food 

consumption were observed at highest tested dose.

Potentially neurotoxic effects were observed at high doses (≥ 285 mg/kg) in the ACN study 

including: gait abnormalities, low arousal, impaired righting reflex, and hunched body posture. 

However, no neurotoxic effects were observed in the SCN at doses up to 77 mg/kg/day. 

Based on the available data, no evidence of genotoxic or immunotoxic effects were identified in 

the database. 

In the 2005 Human Health Risk Assessment, flurprimidol was classified as “not likely to be 

carcinogenic to humans.” For more detail on cancer classification see Section 4.5.3.

The acute toxicity data indicate that flurprimidol has low toxicity (Toxicity Category III and IV) 

via oral, dermal, and inhalation routes of exposure. It is slightly irritating to the skin (Toxicity 

Category IV) and moderately irritating (Toxicity Category III) to the eye. Flurprimidol is not a 

sensitizer in a guinea pig skin sensitization study. 

4.4 Safety Factor for Infants and Children

HED does not recommend any additional safety factors for infants and children. No evidence of 

increased quantitative susceptibility was observed. In the rat developmental study, qualitative 

susceptibility was observed. However, the effects observed in the rat and rabbit developmental, 

and rat 2-generation reproduction studies occur in the presence of maternal toxicity. 

Additionally, these studies have clearly defined NOAEL/LOAELs and the selected points of 

departure (PODs) are protective of all observed adverse effects, including clinical signs 

indicative of neurotoxicity that were observed in the ACN. 

4.4.1 Completeness of the Toxicology Database

The toxicology database for flurprimidol is complete and there are no residual uncertainties with 

regard to assessment of pre- and/or postnatal susceptibility. Acceptable developmental toxicity 

studies in rats and rabbits are available, in addition to an acceptable reproduction study in rats.

4.4.2 Evidence of Neurotoxicity

Clinical signs of neurotoxicity were observed at high doses in the ACN. However, no neurotoxic 

effects were observed in the SCN, or throughout the rest of the flurprimidol database. Based on 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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the available data, selected PODs are protective of any potential neurotoxic effects that may 

result from flurprimidol exposure. 

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

The available data do not provide evidence of any increased quantitative susceptibility in the 

offspring. In the rat developmental study, increased qualitative susceptibility was observed, 

characterized by fetal skeletal abnormalities in the presence of significantly decreased maternal 

body weight gain. However, these effects have clearly defined NOAEL/LOAELS and selected 

PODs are protective of all adverse effects observed in the developing or young animal. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database since adequate exposure data are 

available to assess the occupational and residential exposure resulting from the registered uses. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

A detailed description of the toxicity studies used for selecting toxicity endpoints and PODs for 

various exposure scenarios is presented in Appendix A and summarized in Table 4.5.4.

For acute dietary assessment of the general population, the acute neurotoxicity study in rats was 

selected with a NOAEL of 70 mg/kg/day. The LOAEL is 285 mg/kg/day based on treatment 

related findings at the mid-dose included gait abnormality in both sexes, low arousal, and 

impaired righting reflex in males, and hunched body in females, 7-8 hours after dosing. No other 

effects attributable to a single dose relevant to the general population were observed. 

For acute dietary assessment of females 13 – 49 years old, the developmental toxicity study in 

rats was selected with a NOAEL of 10 mg/kg/day for dams and pups. The LOAEL is 45 

mg/kg/day for dams and pups based on decreased body weight gain (138%) in dams and skeletal 

abnormalities in fetuses. Skeletal abnormalities could be from a single exposure during 

pregnancy and are therefore considered a potential acute effect, and therefore, appropriate for the 

acute dietary endpoint scenario for females of child-bearing age. These effects are also protective 

of abortions observed in the developmental rabbit study.

For chronic dietary exposure and risk assessment, the chronic toxicity study in rats was selected 

with a NOAEL of 3.6 mg/kg/day. The LOAEL is 12.1 mg/kg/day based on increased incidences 

of focal atypia, fatty change, and hepatocellular eosinophilic change in the liver of males. The 

chronic toxicity study in rats is appropriate for the populations and duration of concern, and is 

protective of all other adverse effects observed within the database. 

For short-term incidental oral exposure (1-30 days), the 2-generation reproductive toxicity study 

in rats was selected with a NOAEL of 7.3 mg/kg/day. The LOAEL is 74 mg/kg/day based on 

decreased pup survival and body weights (20-39%). The POD in this study (survival and 
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bodyweight) is appropriate for the age of the population (infant and children) and the duration of 

concern. It is protective of all other short-term effects observed in the database. Intermediate and 

long-term incidental oral exposure assessment are not required because these exposure lengths 

are not expected based on current use patterns. 

A dermal assessment is not required for the flurprimidol. No toxicity was observed up to the 

limit dose in the dermal toxicity study. No quantitative susceptibility was observed in any study. 

Qualitative susceptibility was observed in the rat developmental study, however; as the effects 

occurred in the presence of decreased maternal body weights the available dermal toxicity study 

is considered to be protective as no decreased body weights were observed in that study. 

Additionally, applying the estimated upper bound dermal absorption value to the developmental 

LOAEL would result in an estimated dermal LOAEL near the limit dose (~750 mg/kg/day). 

For short and intermediate-term inhalation exposure, the 13-week inhalation toxicity study in rats 

was selected with a NOAEL of 0.1 mg/L. The LOAEL is 0.4 mg/L based on results in the rangefinding study (MRID 49007302) where goblet cell hyperplasia was observed in nasal level II, III, 

IV, V, and VI of male rats (nasal passages of females were not examined microscopically). The 

inhalation toxicity study was chosen as it is a route-specific study, is protective of all 

developmental and reproductive effects, and appropriate for the duration of concern. Long-term 

inhalation assessment is not required because this exposure lengths are not expected based on 

current use patterns. 

The methods and dosimetry equations described in EPA’s reference concentration (RfC) 

guidance (1994) are suited for calculating HECs based on the inhalation toxicity point of 

departure (NOAEL, LOAEL, or BMDL) for use in MOE calculations. The regional-depositeddose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic 

diameter [MMAD] and geometric standard deviation [g] of aerosols), can be used to estimate 

the different dose fractions deposited along the respiratory tract. The RDDR is also based on 

interspecies differences in ventilation and respiratory-tract surface areas. Thus, the RDDR can be 

used to adjust an observed inhalation particulate exposure of an animal to the predicted 

inhalation exposure for a human. For the subchronic inhalation toxicity study with flurprimidol, 

an RDDR was estimated at 0.223 based on portal-of-entry effects (goblet cell hyperplasia was 

observed in nasal level II, III, IV, V, and VI) at the LOAEL of 0.4 mg/L and a MMAD of 2.62

m and g of 1.7. 

HEC and HED calculations are summarized in Table 4.5.1. The standard interspecies 

extrapolation uncertainty factor can be reduced from 10X to 3X due to the HEC calculation 

accounting for pharmacokinetic (not pharmacodynamic) interspecies differences. The 

intraspecies uncertainty factor remains at 10X. 

For all other routes of exposure a 100X uncertainty factor is applied (interspecies factor of 10X 

and intraspecies factor of 10X). 
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Table 4.5.1: Inhalation HEC and HED Calculation Summary

Population Scenario

Tox duration 

adjustment HEC HED(mg/kg-day; breathing rate specific)

hr/day day/wk mg/L mg/m3 8.3 L/min 16.7 L/min 29 L/min

Occupational Handler 8 5 0.0167 16.73 0.952 1.915 3.326

Residential

Handler NA NA 0.0223 22.3 NA 0.638 NA

Outdoor 

postapplicationNA NA 0.0223 22.3 NA NA NA

Indoor Postapplication NA 7 0.016 15.93 NA

Bystander 24 7 0.004 3.98 NA

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

The risk assessment must address exposures from three major sources: incidental oral, dermal, 

and inhalation and the appropriateness of combining these exposures. These exposure from 

these three routes cannot be combined for flurprimidol as no dermal hazard was identified and 

the inhalation POD is based on route-specific portal of entry effects in the nasal passage. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

In the 2005 Human Health Risk Assessment, flurprimidol was classified as “not likely to be a 

human carcinogen.” Carcinogenicity studies were performed in the rat and the mouse and there 

was no evidence of an increased incidence of tumors in animals treated with flurprimidol. In 

addition, the test article was considered non-mutagenic in 8 genotoxic studies.
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4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4. Summary of Toxicological Doses and Endpoints for Flurprimidol for Use in Human Health 

Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

Safety Factors

RfD/PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(General Population

NOAEL = 70 

mg/kg/day

UFA 10x

UFH 10x

aRfD = 0.7 

mg/kg/day

aPAD = 0.7 

mg/kg/day

Acute Neurotoxicity Study (rats)

MRIDs: 48897501

LOAEL = 285 mg/kg/day, based on based on 

treatment related findings at the mid-dose 

included gait abnormality in both sexes, low 

arousal and impaired righting reflex in males, 

and hunched body in females, 7-8 hours after 

dosing. 

Acute Dietary

(Females 13 to 49 

years of age)

NOAEL = 10 

mg/kg/day

UFA 10x

UFH 10x

aRfD = 0.1 

mg/kg/day

aPAD = 0.1 

mg/kg/day

Developmental Toxicity (rat)

MRIDs: 00147301

LOAEL = 45, based on increased incidences of 

skeletal anomalies in the vertebrae (extra) and 

ribs (extra, rudimentary, cervical).

Chronic Dietary

(All populations)

Parental 

NOAEL= 3.6 

mg/kg/day

UFA 10x

UFH 10x

cRfD = 0.04 

mg/kg/day

cPAD = 0.04 

mg/kg/day

Chronic Toxicity (rat)

MRIDs: 40486003

LOAEL = 12.1, based on increased incidences 

of focal atypia, fatty change, and hepatocellular 

eosinophilic change in the liver of males.

Incidental Oral

Short-Term

(1-30 days)

Offspring 

NOAEL = 7.3 

mg/kg/day

UFA 10x

UFH 10x LOC = 100x

2-Generation Reproductive Toxicity

MRIDs: 00162770

Offspring LOAEL = 74 mg/kg/day, based on 

decreased survival and body weights (20-39%) 

in the pups.

A dermal assessment is not required for the flurprimidol. No toxicity was observed up to the limit dose in the dermal toxicity study. No 

quantitative susceptibility was observed in any study. Qualitative susceptibility was observed in the rat developmental study, however; as 

the effects occurred in the presence of decreased maternal body weights the available dermal toxicity study is considered to be protective as 

no decreased body weights were observed. Additionally, applying the estimated upper bound dermal absorption value to the 

developmental LOAEL would result in an estimated dermal LOAEL near the limit dose (~750 mg/kg/day).

Inhalation

Short-Term

(1-30 days) and 

Intermediate-Term

(1 – 6 months)

NOAEL = 0.1 

mg/kg/day

See Table 4.5.1 

for HEC/HED 

values.

UFA 3x

UFH 10x

FQPA SF = 1X

LOC = 30x

13-Week Inhalation Toxicity (rat)

MRIDs: 49007301, 49007302

LOAEL = 0.4 mg/L based on results in the 

range-finding study (MRID 49007302) where 

goblet cell hyperplasia was observed in nasal 

level II, III, IV, V, and VI of male rats (nasal 

passages of females were not examined 

microscopically).

Cancer (oral) Classification: "Not likely to be a human carcinogen."

Point of Departure (POD) = A data point or an estimated point 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 animals to humans (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFDB= Data base Uncertainty Factor. aPAD = acute 

population adjusted dose. cPAD = chronic population adjusted dose. RfD = reference dose. 
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4.6 Endocrine Disruption

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

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration decision for flurprimidol, EPA 

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

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

flurprimidol is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

of chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.2

 

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the 

final second list of chemicals.

2

2 http://www.epa.gov/endo/
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5.0 Dietary Exposure and Risk Assessment

5.1 Food Residue Profile

There are no currently registered food uses for flurprimidol.

5.2 Summary of Environmental Degradation

The environmental fate data indicates that flurprimidol is mobile and resistant to degradation 

(e.g., half-life > 400 days) in the soil and stable to hydrolysis suggesting the potential for 

leaching and movement to roots for uptake in water by growing plants as suggested by the 

terrestrial field dissipation studies. 

For the tree injection use, it is assumed that flurprimidol will be translocated to the leaves, which 

will degrade, releasing flurprimidol, after falling to the ground. Flurprimidol is stable to 

hydrolysis and resistant to degradation in both aerobic and anaerobic terrestrial systems. Field 

dissipation data for cropped turf plots suggest that much more rapid dissipation was found than 

might be expected from the laboratory studies. 

This could be due to significant volatilization is observed from the plant surfaces than from soil.

Although vapor pressure and Henry’s law constant would suggest that volatilization would not 

be an important dissipation process. Field dissipation data on bare ground sites yields much 

longer dissipation times that are comparable to laboratory estimates, suggesting that plant uptake 

via transpiration or absorption through plant or root surfaces is influencing the dissipation in the 

field.

5.3 Water Residue Profile

The estimated drinking water concentrations (EDWCs) used in the dietary risk assessment were 

provided by EFED and were generated using computer modeling methods. EDWCs were 

calculated using the screening models PRZM-GW (Pesticide Root Zone Model for Groundwater, 

version 1.0, August 31, 2012) for groundwater and Surface Water Concentration Calculator 

(SWCC, version 1.106) for surface water. The models and the descriptions are available at the 

EPA internet site: http://www.epa.gov/oppefed1/models/water/. 

The EDWCs for parent flurprimidol are based upon the maximum rate and number of 

application(s) to obtain the yearly maximum application rate of 3.0 lb a.i./A/year (Table 5.3). 

The recommended EDWCs for groundwater containing flurprimidol are 707 ppb for acute 

exposure and 656 ppb (post-breakthrough average) for chronic exposure. Groundwater estimates 

are higher than previously estimated with the Screening Concentration in Ground Water (SCIGROW) model. A major reason for the difference in estimated concentrations is that PRZM-GW 

considers multiple applications over 30 years, whereas SCI-GROW only considers a single year 

of application. The highest EDWCs estimated using the SWCC for surface water containing 

flurprimidol is 110 ppb for acute exposure, and 19.1 ppb for chronic exposure. Note: The tree 

injection/tree implant uses were not considered in the drinking water assessment, because any 

residues in water from these uses are expected to be lower than the foliar applications of 

flurprimidol.
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The highest EDWCs were from groundwater; therefore, the acute and chronic assessments used 

the groundwater EDWCs of 707ppb and 656 ppb, respectively. 

Table 5.3 Maximum Surface and Ground Water Tier 2 EDWCs from the 

Maximum Use Rates of Flurprimidol

Drinking water source 

(model)

 

1-in-10 year 30-year 

simulation

Acute Chronic Cancer

(μg/L)

Surface Water

(Surface Water 

Concentration Calculator, 

SWCC)a

110 19.1 11.1

Groundwater

(PRZM-GWb)

Peak PostBreakthrough 

Ave

Simulation 

Ave

(μg/L)

707c 656c 326

Florida nursery scenario.

b WI Central Sands Scenario.

c Bold values are the recommended EDWCs.

5.4 Dietary Risk Assessment

5.4.1. Description of Residue Data Used in Dietary Assessment

Updated acute and chronic dietary (drinking water only) exposure and risk assessments were 

conducting using the Dietary Exposure Evaluation Model software with the Food Commodity 

Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption 

data from USDA’s NHANES/WWEIA. The drinking water estimates provided by EFED are 

modeled estimates, and were generated using the most conservative model available for the 

existing uses. The unrefined acute and chronic approach using tolerance level residues to dietary 

risk exposure analysis will not underestimate risk to the general U.S. population or any 

population subgroup.

5.4.2 Percent Crop Treated Used in Dietary Assessment

Percent crop treated refinements were not used in this assessment. 

5.4.3 Acute Dietary Risk Assessment

An unrefined acute dietary (drinking water only) analysis for flurprimidol was conducted that 

directly incorporated potential drinking water residues. The resulting acute drinking water risk 

estimates are below HED’s level of concern (<100% aPAD) at the 95th percentile of the exposure 

distribution for the general U.S. population 6% aPAD, and all population subgroups. The aPAD 

is lower for females 13 to 49 years old. Although all infants have the highest exposure estimate 

(0.120747 mg/kg/day; 17% aPAD), the population subgroup with the highest risk estimate is 
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females 13 to 49 years old, which utilize 38% of the aPAD (0.038477 mg/kg/day) at the 95th

percentile of exposure. The detailed results for the general population and all population 

subgroups are shown below in Table 5.4.6.

5.4.4 Chronic Dietary Risk Assessment

The unrefined chronic dietary (drinking water only) risk estimate utilizes 34% of the cPAD for 

the U.S. population. The estimated risk for the most highly exposed population subgroup all 

infants <1 year is 86% of the cPAD. Thus, chronic dietary exposure to flurprimidol for all 

population subgroups is not of concern. The detailed results for the general population and all 

population subgroups are shown below in Table 5.4.6.

5.4.5 Cancer Dietary Risk Assessment

Flurprimidol currently has no registered food uses and flurprimidol was classified as “not likely 

to be a human carcinogen”; therefore a cancer dietary (drinking water only) assessment is not 

required. 

5.4.6 Dietary Summary Table

The acute and chronic dietary exposure and risks for flurprimidol are summarized below.

DEEM-FCID Model inputs and outputs for acute and chronic dietary exposure estimates are 

attached in Appendix B.

Table 5.4.6. Summary of Dietary (Drinking Water Only) Exposure and Risk for Flurprimidol1

Population Subgroup

aPAD 

(mg/kg

/day)

Acute Results

95th Percentile Chronic Results Cancer Results

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

General U.S. 

Population

0.7

0.038551 6 0.013736 34

Not Applicable

All Infants (<1 year 

old) 0.120747 17 0.035418 89

Children 1-2 years old 0.059446 8 0.019815 50

Children 3-5 years old 0.048236 7 0.016695 42

Children 6-12 years 

old 0.036856 5 0.012040 30

Youth 13-19 years old 0.032105 6 0.010017 25

Adults 20-49 years old 0.037936 5 0.013705 34

Adults 50-99 years old 0.033793 5 0.013548 34

Females 13-49 years 

old 0.1 0.038477 38 0.013654 34

1 Values for the population with the highest risk are bolded. 
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6.0 Residential Exposure and Risk Estimates

There are existing residential uses that have been assessed in this document to reflect updates to 

HED’s 2012 Residential SOPs3along with policy changes for body weight assumptions. 

6.1 Residential Handler Exposure/Risk Estimates

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment.

The flurprimidol quantitative exposure/risk assessment developed for residential handlers is 

based on the following scenarios: 

 Mixing/loading/applying liquids with a manually-pressurized handwand, 

 Mixing/loading/applying liquids with a hose-end sprayer,

 Mixing/loading/applying liquids with a backpack,

 Mixing/loading/applying liquids with a sprinkler can,

 Mixing/loading/applying wettable powders in water-soluble packaging with a manuallypressurized handwand,

 Mixing/loading/applying wettable powders in water-soluble packaging with a hose-end 

sprayer,

 Mixing/loading/applying wettable powders in water-soluble packaging with a backpack,

 Mixing/loading/applying wettable powders in water-soluble packaging with a sprinkler can,

 Loading/applying granulars with a push-type spreader,

 Loading/applying granulars with a belly grinder,

 Loading/applying granulars with a spoon,

 Loading/applying granulars with a cup,

 Loading/applying granulars with hand dispersal, and 

 Loading/applying granulars with a shaker can.

HED anticipates that residential handler exposure from mixing/loading liquids for tree injection 

use is less than would be anticipated from occupational handler exposure for tree injection. It is

not anticipated that as many trees would be treated per day in a residential setting than in an 

occupational setting. Therefore, the occupational handler assessment that was conducted for this 

chemical is considered protective of the residential handler exposures and, accordingly, a 

quantitative residential handler assessment for this scenario was not conducted. 

Table 6.1.1 provides a summary of the residential hander exposures and risk estimates for 

flurprimidol. All inhalation exposure risk estimates are greater than HED’s LOC (MOEs ≥ 30)

at baseline attire (i.e., no respirator). 

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Table 6.1.1 Residential Handler Non-cancer Exposure and Risk Estimates for Flurprimidol.

Exposure Scenario Crop or Target

Inhalation Unit 

Exposure (mg/lb ai)

Maximum 

Application 

Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

M/L/A liquids with 

a manuallypressurized 

handwand

Gardens/Trees 0.018

0.000024 lb 

ai/ft2 1200 ft2 0.0000065 99,000

M/L/A liquids with 

a hose-end sprayer Gardens/Trees 0.0014 0.000024 lb 

ai/ft2 1200 ft2 0.0000005 1,300,000

M/L/A liquids with 

a hose-end sprayer Turf 0.022 1.5 lb ai/A 0.5 acres 0.00021 3,100

M/L/A liquids with 

a manuallypressurized 

handwand

Turf 0.018

0.008 lb 

ai/gallon 5 gallons 0.000009 71,000

M/L/A liquids with a 

backpack Gardens/Trees 0.14 0.000024 lb ai/ft2 1200 ft2 0.00005 13,000

M/L/A liquids with 

Sprinkler can Gardens/Trees 0.0014 0.000024 lb 

ai/ft2 1200 ft2 0.0000005 1,300,000

M/L/A liquids with 

sprinkler can Turf 0.022 0.000034 lb 

ai/ft2 1000 ft2 0.0000094 68,000

M/L/A liquids with 

backpack Turf 0.14 0.008 lb 

ai/gallon 5 gallons 0.00007 9,100

M/L/A wettable 

powders in watersoluble packaging 

with a manuallypressurized 

handwand

Gardens/Trees 0.018 0.000024 lb 

ai/ft2 1200 ft2 0.0000065 99,000

M/L/A wettable 

powders in watersoluble packaging 

with a hose-end 

sprayer

Gardens/Trees 0.034

0.000024 lb 

ai/ft2 1200 ft2 0.000012 52,000

M/L/A wettable 

powders in watersoluble packaging 

with a hose-end 

sprayer

Turf 0.034

1.5 lb ai/A 0.5 acres 0.00032 2,000

M/L/A wettable 

powders in watersoluble packaging 

with a manuallypressurized 

handwand 

Turf 0.018

0.008 lb 

ai/gallon 5 gallons 0.000009 71,000

M/L/A wettable 

powders in watersoluble packaging 

with a backpack

Turf 0.018

0.008 lb 

ai/gallon 5 gallons 0.000009 71,000

M/L/A wettable 

powders in water- Gardens/Trees 0.034 0.000024 lb 

ai/ft2 1200 ft2 0.000012 52,000
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Table 6.1.1 Residential Handler Non-cancer Exposure and Risk Estimates for Flurprimidol.

Exposure Scenario Crop or Target

Inhalation Unit 

Exposure (mg/lb ai)

Maximum 

Application 

Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

soluble packaging 

with Sprinkler can

M/L/A wettable 

powders in watersoluble packaging 

with Sprinkler can

Turf 0.034 0.000034 lb ai/ft2

1000 ft2 0.000014 44,000

M/L/A wettable 

powders in watersoluble packaging 

with a backpack

Gardens/Trees 0.018

0.000024 lb 

ai/ft2 1200 ft2 0.0000065 99,000

M/L/A granulars 

with a push-type 

spreader

Gardens/Trees 0.0026 0.000024 lb 

ai/ft2

1200 ft2 0.00000094 680,000

M/L/A granulars 

with a push-type 

spreader

Turf 0.0026 1.5 lb ai/A 0.5 acres 0.000024 26,000

M/L/A granulars 

with a belly grinder Turf 0.039 0.000034 lb 

ai/ft2 1200 ft2 0.00002 32,000

M/L/A granulars 

with a spoon Gardens/Trees 0.087 0.000024 lb 

ai/ft2 1200 ft2 0.000031 20,000

M/L/A granulars 

with a spoon Turf 0.087 0.000034 lb 

ai/ft2

100 ft2 0.0000037 170,000

M/L/A granulars 

with a cup Gardens/Trees 0.013 0.000024 lb 

ai/ft2 1200 ft2 0.0000047 140,000

M/L/A granulars with 

a cup

Turf 0.013 0.000034 lb 

ai/ft2 100 ft2 0.00000055 1,200,000

M/L/A granulars with 

hand dispersal Gardens/Trees 0.38 0.000024 lb ai/ft2 1200 ft2 0.00014 4,700

M/L/A granulars with 

hand dispersal Turf 0.38 0.000034 lb ai/ft2 100ft2 0.000016 40,000

M/L/A granulars with 

a shaker can Gardens/Trees 0.013 0.000024 lb ai/ft2 1200 ft2 0.0000047 140,000

M/L/A granulars with 

a shaker can Turf 0.013 0.000034 lb ai/ft2 100 ft2 0.00000055 1,200,000

1 Based on registered labels (See Table 3.3).

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

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled 

(A/day or gallons/day) ÷ BW (80 kg).

4 Inhalation MOE = Inhalation NOAEL (HED = 0.638 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

6.2 Residential Post-application Exposure/Risk Estimates

Residential post-application dermal exposure for adults or children was not assessed for 

flurprimidol because there is no identified dermal hazard. Also, residential post-application 

incidental oral exposure for children was not assessed because flurprimidol label directions 

indicate that it is applied to turf for edging/banding applications along the perimeter of lawns, 

landscape beds, sidewalks, curbs, parking lots, driveways, posts, mailboxes, building structures, 

gravestones, and fences. As detailed in the Lawns/Turf 2012 Residential SOPs, residential postapplication assessments do not need to be performed if label directions indicate that the turf use 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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is an edging use (e.g., along fence rows), a foundation perimeter treatment, or a specific spot 

treatment. These types of uses may result in residues on turf; however, because of the low 

potential for contact, the residential exposure is expected to be negligible.

Turf Transferable Residue (TTR): In accordance with the updated Part 158 data requirements, 

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. Since there is 

no hazard via the dermal route of exposure, a non-cancer dermal post-application risk assessment 

was not performed for flurprimidol. Further, no incidental oral assessment for the registered turf 

uses is required for the reasons described above. Therefore, TTR studies are not needed for 

flurprimidol at this time. 

6.3 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to exposures (e.g., children playing on 

lawns where residues have deposited next to treated fields). The potential risk estimates from 

these residues can be calculated using drift modeling coupled with methods employed for 

residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include 

assessing exposures for children (1 to 2 years old) and adults who have contact with turf where 

residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. 

Aside from the predicted residues available for transfer, the routes of exposure and assessment 

methodology is analogous to how exposures to turf products are considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, 

a residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of flurprimidol. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift® (v2.1.1) model. 

Exposures were considered for 50 feet wide lawns where the nearest side of the property was 

directly adjoining the treated field (at field edge) and at varied distances up to 300 feet 

downwind of a treated field. Once the deposited residue values were determined, the remainder 

of the spray drift assessment was based on the algorithms and input values specified in the 

recently revised (2012) Standard Operating Procedures For Residential Risk Assessment 

(SOPs). 

 

A screening approach was developed for situations where specific label guidance for 

application parameters is not available.4,5 AgDrift® is appropriate for use only when applications 

 

4http://www.agdrift.com/ 

5 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk 

assessors should be aware and characterize these appropriately.
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are made by aircraft, airblast sprayers, and groundboom sprayers. When AgDrift® was 

developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model 

and represent each equipment type and use under varied conditions. The screening options 

specifically recommended in this methodology were selected because they are plausible and 

represent a reasonable upper bound level of drift for common application methods in agriculture. 

In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use 

pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions 

(e.g., aerial applications are not allowed). Section 6.4.1 provides the screening level drift related 

risk estimates. These drift estimates represent plausible options based on the available pesticide 

labels. 

6.3.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening level agricultural application scenarios. Flurprimidol is used on perennial 

turfgrass (cool and warm season) on golf courses and turf, landscape/woody ornamental plants, 

ornamental trees and ornamental plants grown in containers in nurseries, greenhouses, and 

shadehouses. The spray drift assessment was conducted using the highest registered application 

rate of 1.5 lb ai/A for use on golf courses. The recommended drift scenario screening level 

options are listed below: 

 Groundboom applications are based on the AgDrift option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

There are no short- or intermediate-term dermal PODs. Only incidental oral risk estimates were 

evaluated. The total applicable LOC is 100, so MOEs <100 would be of concern. Children (1 to 

<2 years old) incidental oral risk estimates from exposure to flurprimidol related to spray drift 

result in no risks of concern at the field edge for groundboom applications (Table 6.4.1). 

Table 6.4.1. Children (1 to < 2 years old) Incidental Oral Risk Estimates (MOEs) 

Related to Spray Drift Exposure for Flurprimidol.

1

Crop/Rate 

Group

Spray Type/ Nozzle 

Configuration

Application 

Rate (lb 

ai/A)

Estimated 

or 

Adjusted 

TTRt

(ug/cm2)

At Edge

HtM MOE

Golf Courses

Groundboom High Boom Very fine 

to Fine 1.5 0.166725 1,700

1 The spray drift assessment was conducted using the highest registered application rate of 1.5 lb ai/A for use on golf courses. 

6.4 Residential Bystander Post-Application Inhalation Exposure

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

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

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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

subsequent Volatilization Screening Analysis 

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

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

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

flurprimidol.

7.0 Combined Exposure/Risk Characterization

Routes of exposure cannot be combined for flurprimidol as no dermal hazard was identified and 

the inhalation POD is based on route-specific portal of entry effects in the nasal passage. 

Additionally, as discussed in Section 6.2, residential post-application incidental oral exposure for 

children was not assessed as residential post-application exposure is expected to be negligible 

based on the use pattern; therefore there is only one source of oral exposure (drinking water). 

Therefore, no assessment for combined routes of exposure was conducted at this time.

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 flurprimidol and any other substances. For the purposes of this assessment, therefore, EPA 

has not assumed that flurprimidol 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 and Risk Estimates

9.1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the registered uses. 

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

following scenarios: 
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 Mixing/loading granulars to support tractor-drawn spreader applications,

 Mixing/loading liquids for aerial applications,

 Mixing/loading liquids for groundboom applications,

 Mixing/loading liquids for airblast applications,

 Mixing/loading liquids for chemigation applications,

 Mixing/loading liquids for tree injection applications,

 Mixing/loading wettable powders in water-soluble packets for groundboom applications,

 Applying sprays for aerial applications,

 Applying sprays for airblast applications,

 Applying sprays for groundboom applications,

 Applying granulars for tractor-drawn spreader applications,

 Flagging to support aerial spray applications,

 Mixing/loading/applying liquids for backpack applications,

 Mixing/loading/applying liquids for manually-pressurized handwand applications,

 Mixing/loading/applying liquids for mechanically-pressurized handgun applications,

 Mixing/loading/applying wettable powders in water-soluble packets for backpack 

applications,

 Mixing/loading/applying wettable powders in water-soluble packets for manuallypressurized handwand applications,

 Mixing/loading/applying wettable powders in water-soluble packets for mechanicallypressurized handgun applications,

 Loading/applying granulars for backpack applications,

 Loading/applying granulars for belly grinder applications,

 Loading/applying granulars for rotary spreader applications.

Tree injection is not typically assessed by HED because the Agency has no exposure data for the 

tree injection application scenario. In this assessment, however, HED did assess exposure from 

mixing/loading for the tree injection scenario. Use information specific to this chemical was not 

available for this scenario; therefore, HED used available tree injection assumptions from a 

previous ORE assessment for dinotefuran (O’Keefe, B., D378123, 2/28/2011) to represent the 

same scenario. The registered label (Reg. No. 67690-34) specifies 2 ml per injection site (or 

0.0024 lb ai/injection site) for trees with diameters over 12 inches as the maximum application 

rate. Based on assumptions used in the dinotefuran tree injection assessment, it is assumed that 

one applicator can make 600 trunk injections per day. This assessment assumes then that the 

maximum amount of product handled would be 1.46 lb ai/day (0.0024 lb ai/injection hole x 600 

injection holes/day) by one applicator.

In this assessment, the tree implant application scenario was not assessed because little to no 

exposure is expected from this use. The label states that each implant should be firmly seated 

into the tree trunk one-inch below the bark. Holes should be drilled with a 3/8” self-centering 

(brad point) spiral bit. Stop collars or tape can be used to set hole depths (1 inch plus bark 

thickness) on the drill bit. Each hole should be filled or flushed with water from a squirt bottle 

prior to implant insertion. Direct exposure to this substance is minimal because the product is in 

a self-contained device.
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The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for human 

flaggers where appropriate, agricultural aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeved shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm inhalation MOEs are greater than HED’s LOC (i.e., MOEs > 30) with baseline attire. . 

Table 9.1 provides the worst-case scenarios for the registered uses for flurprimidol. The MOEs 

range from 1,100 to 900,000. 

Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

Mixer/Loader

M/L Granules for Aerial 

Applications Nursery 1.7 1.5 60 0.00191 1,700

M/L Granules for 

Tractor-Drawn Spreader 

Application

Golf Course

(fairways, tees, greens) 1.7 1.0 40 0.00085 3,900

M/L Granules for 

Tractor-Drawn Spreader 

Application

Golf Course

(tees and

greens only)

1.7 0.75 5 0.0000798 42,000

M/L Granules for 

Tractor-Drawn Spreader 

Application

Nursery 1.7 1.5 60 0.00191 1,700
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

M/L Granules for 

Tractor-Drawn Spreader 

Application

Greenhouse 1.7 1.5 60 0.00191 1,700

M/L Liquids for Aerial 

Application Nursery 0.219 0.55 60 0.0000904 21,000

M/L Liquids for 

Airblast Application Nursery 0.219 0.55 20 0.0000301 64,000

M/L Liquids for 

Chemigation

Application

Greenhouse 0.219 0.55 60 0.0000904 21,000

M/L Liquids for 

Chemigation 

Application

Nursery 0.219 0.55 60 0.0000904 21,000

M/L Liquids for 

Groundboom 

Application

Golf Course

(tees and greens only) 0.219 0.25 5 0.00000343 560,000

M/L Liquids for 

Groundboom 

Application

Golf Course

(fairways, tees, greens) 0.219 0.75 40 0.0000821 23,000

M/L Liquids for 

Groundboom 

Application

Nursery 0.219 0.55 60 0.0000904 21,000

M/L Liquids for 

Groundboom 

Application

Greenhouse 0.219 0.55 60 0.0000904 21,000

M/L Liquids for Tree 

Injection Trees 0.219 1.46 lb ai/day 1 day 0.000004 480,000

M/L Wettable Powders 

in Water-Soluble 

Packets for 

Groundboom 

Application

Golf Course

(tees and greens only)

0.24

(EC) 0.25 5 0.00000375 890,000

M/L Wettable Powder 

in Water-Soluble 

Packets for 

Groundboom 

Application

Golf Course

(fairways, tees, greens)

0.24

(EC) 0.75 40 0.00009 37,000

Applicator

Applying Sprays for 

Aerial Application Nursery 0.0049(EC) 0.55 60 0.00000203 470,000

Applying Sprays

for Airblast Application Nursery 4.71 0.55 20 0.000648 1,500
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

Applying Sprays for 

Groundboom 

Application

Golf Course

(tees and greens Only) 0.34 0.25 5 0.00000531 180,000

Applying Sprays for 

Groundboom 

Application

Golf Course

(fairways, tees, greens) 0.34 0.75 40 0.000128 7,400

Applying Sprays for 

Groundboom 

Application

Nursery 0.34 0.55 60 0.00014 6,800

Applying Sprays for 

Groundboom 

Application

Greenhouse 0.34 0.55 60 0.00014 6,800

Applying Granules for 

Tractor-Drawn Spreader 

Application

Greenhouse 1.2 1.5 60 0.00135 2,500

Applying Granules for 

Aerial Application Nursery 1.3(EC) 1.5 60 0.00146 2,300

Applying Granules for 

Tractor-Drawn Spreader 

Application

Golf course (fairways, 

tees, greens) 1.2 1.0 40 0.0006 5,500

Applying Granules for 

Tractor-Drawn Spreader 

Application

Golf course,

(tees and

greens only)

1.2 0.75 5 0.0000563 59,000

Applying Granules for 

Tractor-Drawn Spreader 

Application

Nursery 1.2 1.5 60 0.00135 2,500

Flagger for Aerial 

Application for Liquids Nursery 0.35 0.55 60 0.000145 23,000

Flagging for Aerial 

Application for 

Granules

Nursery 0.15 1.5 60 0.000169 20,000

Mixer/Loader/Applicator

M/L/A Foliar Spray for 

Backpack

Application

(Broadcast)

Greenhouse 140 0.00165 lb 

ai/gallon

40 

gallons 0.000116 17,000

M/L/A Foliar Spray for 

Backpack Application 

(Broadcast Foliar)

Greenhouse 140 0.00165 lb 

ai/gallon

40 

gallons 0.000116 17,000

M/L/A Foliar Spray for 

Backpack Application

Nursery 140 0.00165 lb 

ai/gallon

40 

gallons 0.000116 17,000
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

M/L/A Foliar Spray for 

Backpack Application, 

Ground/Soil- Directed

Nursery 2.58 0.00165 lb 

ai/gallon

40 

gallons 0.00000213 900,000

M/L/A Foliar Spray for 

Backpack Application

Landscaping, 

trees/shrubs/bushes 140 0.005 lb ai/gallon

40 

gallons 0.00035 5,500

M/L/A Foliar Spray for 

Backpack Application

Landscaping, 

plants/flowers 140 0.005 lb ai/gallon

40 

gallons 0.00035 5,500

M/L/A Liquids with 

Backpack for Spot 

Treatment

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.) 2.58 0.008 lb ai/gallon

40 

gallons 0.0000103 190,000

M/L/A Liquids with 

Manually-Pressurized 

Handwand

Greenhouse

30 0.00165 lb 

ai/gallon

40 

gallons 0.0000248 130,000 M/L/A Liquids with 

Manually-Pressurized 

Handwand

Nursery

M/L/A Liquids with 

Manually-Pressurized 

Handwand

Landscaping, 

trees/shrubs/bushes

30 0.005 lb 

ai/gallon

40 

gallons 0.000075 44,000 Landscaping, 

plants/flowers

M/L/A Liquids with 

Manually-Pressurized 

Handwand

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.) 30 0.008 lb ai/gallon

40 

gallons 0.00012 28,000

M/L/A Liquids with 

MechanicallyPressurized Handgun 

for Broadcast 

Application

Greenhouse 120 0.00165 lb 

ai/gallon

1,000 

gallons 0.00248 1,300

M/L/A Liquids with 

MechanicallyPressurized Handgun 

for Drench/Soil-

/Ground-directed

Greenhouse 120 0.00165 lb 

ai/gallon

1,000 

gallons 0.00248 1,300

M/L/A Liquids with 

MechanicallyPressurized Handgun

Golf course (tees and 

greens only) 1.9 0.25 5 0.0000298 64,000

M/L/A Liquids with 

MechanicallyPressurized Handgun

Golf course (fairways, 

tees, greens) 1.9 0.75 5 0.0000891 21,000
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

M/L/A Liquids with 

MechanicallyPressurized Handgun 

for Broadcast 

Application Nursery 3.9 0.00165 lb 

ai/gallon

1,000 

gallons 0.0000805 41,000 M/L/A Liquids with 

MechanicallyPressurized Handgun 

for Drench/Soil-

/Ground-directed

M/L/A Liquids with 

MechanicallyPressurized Handgun

Landscaping, 

trees/shrubs/bushes 3.9 0.005 lb 

ai/gallon

1,000 

gallons 0.000244 14,000

M/L/A Liquids with 

MechanicallyPressurized Handgun

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.) 1.9 1.5 5 acres 0.000179 11,000

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Backpack

Landscaping, 

trees/shrubs/bushes

140 0.005 lb 

ai/gallon

40 

gallons 0.00035 5,500

Landscaping, 

plants/flowers

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Backpack for Spot 

Treatment

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.) 2.58 0.008 lb ai/gallon

40 

gallons 0.0000103 190,000

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Manually-Pressurized 

Handwand

Application

Landscaping, 

trees/shrubs/bushes

30 0.005 lb 

ai/gallon

40 

gallons 0.000075 44,000 Landscaping, 

plants/flowers

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Mechanicallypressurized Handgun

Golf course (tees and 

greens only) 18 0.25 5 0.000281 6,800

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Mechanicallypressurized Handgun

Golf course (fairways, 

tees, greens) 18 0.75 5 0.000844 2,300
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Mechanicallypressurized Handgun

Landscaping, 

trees/shrubs/bushes 3.9 0.005 lb ai/gallon

1,000 

gallons 0.000244 14,000

M/L/A Wettable 

Powders in WaterSoluble Packets with 

Mechanicallypressurized Handgun

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

18 1.5 5 0.00169 1,100

Loading/Applying

Loading/Applying 

Granules for Backpack 

for Ground/SoilDirected Application

Greenhouse

23.8 1.5 1 0.000446 4,300 Loading/Applying 

Granules for Backpack 

for Ground/SoilDirected Application

Nursery

Loading/Applying 

Granules for Belly 

Grinder Application

Greenhouse 62 1.5 1 0.00116 2,900

Loading/Applying 

Granules for Belly 

Grinder Application

Nursery 62 1.5 1 0.00116 2,900

Loading/Applying 

Granules for Belly 

Grinder Application

Landscaping, 

trees/shrubs/bushes

62 1.5 1 0.00116 2,900

Loading/Applying 

Granules for Belly 

Grinder Application

Landscaping, 

plants/flowers

Loading/Applying 

Granules for Belly 

Grinder Application

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

Loading/Applying 

Granules for Rotary 

Spreader Application

Greenhouse 

(ornamentals, roses, 

cut flowers, container 

stock, vegetables)

10 1.5 5 0.000938 2,000

Loading/Applying 

Granules for Rotary 

Spreader Application

Golf course (tees and 

greens only) 10 0.75 5 0.000469 4,100
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Table 9.1. Short- and Intermediate- term Occupational Handler Exposure and Risk Estimates for 

Flurprimidol.

Exposure Scenario Crop or Target

Baseline 

Inhalation 

Unit 

Exposure1

μg/lb ai

Maximum

Application 

Rate2

lb ai/A

(unless 

otherwise 

noted)

Area 

Treated 

or 

Amount 

Handled 

Daily3

Acres

(unless 

otherwis

e noted)

Dose4

mg/kg/day

Short- and 

Intermediate-term

Inhalation

MOE5

LOC = 30

Loading/Applying 

Granules for Rotary 

Spreader Application

Golf course (fairways, 

tees, greens) 10 1.0 5 0.000625 3,100

Loading/Applying 

Granules for Rotary 

Spreader Application

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.) 10 1.5 5 0.000938 2,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: 

Baseline, Eng. Controls.

2 Based on registered labels (See Table 3.3).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) x Application Rate (lb ai/A or gallon) x Area treated or Amount Handled (A/day or 

gallons/day) / Body Weight (80 kg).

5 Inhalation MOE = Inhalation NOAEL (0.952, 1.92, or 3.92 mg/kg/day)/Inhalation Dose (mg/kg/day).

9.2 Occupational Post-application Exposure/Risk Estimates

Occupational post-application dermal exposure was not assessed for flurprimidol because there 

is no identified systemic dermal hazard. Based on the Agency's current practices, a quantitative 

occupational post-application inhalation exposure assessment was not performed for flurprimidol

at this time. 

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. Since there is no hazard via the 

dermal route of exposure, a non-cancer dermal post-application risk assessment was not 

performed for flurprimidol. Therefore, DFR studies are not needed for flurprimidol at this time. 

If the PODs change, the need for DFR studies may be reevaluated in the future to refine the postapplication assessment.

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency has 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

Page 36 of 48

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

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-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 flurprimidol.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments.

Although a quantitative occupational post-application 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 post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements.[40 CFR 170.110, (3) (Restrictions associated with pesticide 

applications)]
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for the Non-Food Use of flurprimidol are in Table 1. Use of 

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

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 (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 28-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

cr

cr

nr

yes

cr

yes

yes

yes

no (a)

yes

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

cr

cr

cr

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation – bacterial 870.5300 

Mutagenicity—Gene Mutation - mammalian

870.5375 Mutagenicity—Structural Chromosomal 

870.5395 Mutagenicity—Other Genotoxic Effects

870.5550 Mutagenicity—Unscheduled DNA Synthesis

yes

yes

yes

yes

no

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)

870.6200a Acute Neurotox. Screening Battery (rat)

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

870.6300 Develop. Neuro

cr

yes

yes

cr

no

yes

yes

no

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

Yes

cr

yes

yes

yes

yes

(a) The 21 day dermal study is suitable for risk assessment based on the current use pattern, and a 90-day dermal study is 

not required.

(b) Not required at this time.
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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A.2 Toxicity Profiles

Table A.2.1 Acute toxicity Profile – Flurprimidol

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

870.1100 Acute oral -rat 00117933 LD50 = 914 (M) 

or 709 (F) mg/kg

III

870.1200 Acute dermal-rabbit 00010214 LD50 = >500 

mg/kg

III

870.1300 Acute inhalation-rat 40401009 LC50 = >5.231 

mg/L

IV

870.2400

Acute eye irritation-rabbit 00248752 Moderate eye 

irritant

III

870.2500 Acute dermal irritation-rabbit 40401008 Slight dermal 

irritant

IV

870.2600 Skin sensitization-guinea pig 00162766 Not a sensitizer N/A

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

870.3100 1982-90-Day oral 

toxicity-rat

Acceptable/Nonguideline

0, 0.0025, 0.009, 0.03, 

0.1%

mg/kg/day =

M: 0, 1.68, 6.04, 

20.39, 68.34

F: 0, 1.98, 7.13, 24.37, 

78.47

00117945 NOAEL (mg/kg/day): 68.34

LOAEL (mg/kg/day): not 

determined

870.3100 1982-90-Day oral 

toxicity -mouse

Unacceptable/Guideline

0, 0.010, 0.045, 0.20%

mg/kg/day=

0, 15, 67.5, 300

00162767 NOAEL (mg/kg/day): 300

LOAEL (mg/kg/day): not 

determined

870.3150 1986-90-Day oral 

toxicity -dog

Acceptable/Guideline 

mg/kg/day=

0, 0.5, 1.5, 30

00162768 NOAEL (mg/kg/day): 1.5

LOAEL (mg/kg/day): 30 

based on decreased adrenal weights, 

increased incidences of eosinophilic 

degeneration and vacuolation in the 

zona fasciculata in both sexes and 

increased cortical atrophy as well as 

incidences in eosinophilic

degeneration in the zona reticularis 

in males.

870.3150 1986-90-Day oral 

toxicity -dog

Acceptable/Guideline

mg/kg/day=

0, 2, 10, 80 

00158239 NOAEL (mg/kg/day): 2

LOAEL (mg/kg/day): 10 

based on small adrenals in males, 

decreased adrenal weights in both 

sexes, and increased incidences of 

adrenal cortical vacuolation in 

females.
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

870.3200 1986-21-Day dermal 

toxicity -rabbit

Acceptable/Guideline

mg/kg/day=

0, 500, 1000

00162769 Systemic NOAEL (mg/kg/day): 

1000 

Systemic LOAEL (mg/kg/day): not 

determined

Dermal NOAEL (mg/kg/day): not 

determined

Dermal LOAEL (mg/kg/day): 500 

based on transient dermal irritation 

in the males.

870.3465 13-Week Inhalation –

Rat

Acceptable/Guideline

0, 0.010, 0.035, or 0.1 

mg/L

49007301

49007302

NOAEL = 0.1 mg/L

LOAEL = 0.4 mg/L based on results 

in the range-finding study (MRID 

49007302) where goblet cell 

hyperplasia was observed in nasal 

level II, III, IV, V, and VI of male 

rats (nasal passages of females were 

not examined microscopically).

870.3700a 1985-Prenatal 

developmental -rat

Acceptable/Guideline

mg/kg/day= 

0, 2.5, 10, 45, 200

00147301 Maternal NOAEL (mg/kg/day): 10 

Maternal LOAEL (mg/kg/day): 45 

based on decreased body weight 

gains and food consumption.

Developmental NOAEL 

(mg/kg/day): 10

Developmental LOAEL 

(mg/kg/day): 45 

based on increased incidences of 

microphthalmia, and skeletal 

anomalies in the vertebrae (extra) 

and ribs (extra, rudimentary, 

cervical).

870.3700b 1985-Prenatal 

developmental -rabbit

Acceptable/Nonguideline

Main Study

mg/kg/day:

0, 1.7, 9.0, 45 

Range-finding study

mg/kg/day:

0, 2.5, 7.5, 20, 60

00147300 Maternal NOAEL (mg/kg/day): 45

Maternal LOAEL (mg/kg/day): 60

based on the results of a rangefinding study in which anorexia, 

abortion, weight loss, and decreased 

food consumption was observed.

Developmental NOAEL (m/kg/day): 

45

Developmental LOAEL 

(mg/kg/day): 60 based on abortion

870.3800 1986-Reproduction and 

fertility effects -rat 

0, 25, 100, 1000ppm

mg/kg/day =

0, 1.8, 7.3, 74 

00162770 Parental NOAEL (mg/kg/day): 7.3

Parental LOAEL (mg/kg/day): 74
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

Acceptable/Guideline based on clinical signs of toxicity in 

the P females during gestation and 

lactation, decreased body weights, 

decrease relative liver weights, 

hepatocellular hypertrophy, and 

increased incidence of fatty change 

and vacuolation in the liver in males.

Reproductive NOAEL (mg/kg/day): 

7.3 

Reproductive LOAEL (mg/kg/day): 

74 based on decreased mating, 

fertility, and fetal survival 

(stillbirths) in both generations and 

increased incidence of persistent 

vaginal estrous and no corpora lutea.

Offspring NOAEL (mg/kg/day): 7.3 

Offspring LOAEL (mg/kg/day): 74 

based on decreased survival and 

body weights in the pups.

870.4100b 1987-Chronic toxicity -

dog

Acceptable/Guideline

mg/kg/day=

0, 0.5, 1.5, 7.0, 30.0

40486001 NOAEL (mg/kg/day): 7.0 

LOAEL (mg/kg/day): 30.0 

based on microscopic lesions in the 

adrenal glands, reduced response to 

ACTH in both sexes, and decreased 

adrenal weights in males.

870.4200b 1988-Carcinogenicity

-mouse

Unacceptable/Guideline

0, 10, 80, 600 ppm

mg/kg/day=

M: 0, 1.3, 9.8, 75.7 

F: 0, 1.4, 11.2, 84.0 

40513701 NOAEL (mg/kg/day): 75.7 

LOAEL (mg/kg/day): not 

determined.

No evidence of carcinogenicity

870.4300 1987-

Chronic/Carcinogenicity-rat

Unacceptable/Guideline

0, 1000 ppm 

mg/kg/day=

M: 0, 43.1

F: 0, 51.7

40486002 NOAEL (mg/kg/day): not 

determined 

LOAEL (mg/kg/day): 43.1/51.7

based on increased liver weights and 

increased incidences of focal 

basophilic atypia, fatty change, and 

hepatocellular eosinophilic change in 

the liver of both sexes

No evidence of carcinogenicity

870.4300 1987-

Chronic/Carcinogenicity-rat

0, 25, 90, 300, 1000 

ppm

mg/kg/day=

40486003 NOAEL (mg/kg/day): 3.6

LOAEL (mg/kg/day): 12.1

based on increased incidences of 

focal atypia, fatty change, and 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

Acceptable/Guideline

M: 0, 1.0, 3.6, 12.1, 

41.2 

F: 0, 1.2, 4.4, 14.5, 

49.3 

hepatocellular eosinophilic change in 

the liver of males.

No evidence of carcinogenicity

870.5100 1987-Bacterial Gene 

Mutation 

Acceptable/Guideline

312.5, 625, 1250, 2500, 

5000 μg/plate

40184406 NEGATIVE

There was no evidence of induced 

mutant colonies over background in 

the presence or absence of S9.

870.5100 1987-Bacterial Gene 

Mutation

Acceptable/Guideline

312.5, 625, 1250, 2500, 

5000 μg/plate

40184407 NEGATIVE

There was no evidence of induced 

mutant colonies over background in 

the presence or absence of S9.

870.5100 1984-Bacterial Gene 

Mutation 

Acceptable/Guideline

100, 500, 1000, 2500, 

5000 μg/plate

00154366 NEGATIVE

There was no evidence of induced 

mutant colonies over background in 

the presence or absence of S9.

870.5100 1982-Bacterial Gene 

Mutation

Acceptable/Guideline

0.1-1000 μg/mL 

(gradient plate)

00117939 NEGATIVE

There was no evidence of induced 

mutant colonies over background in 

the presence or absence of S.

870.5300 1982-In Vitro Forward 

Mutation

Acceptable/Guideline

1, 25, 50, 75. 100, 125, 

150, 175 μg/mL

00154365 NEGATIVE

There was no concentration-related 

positive response of induced mutant 

colonies over background.

870.5375 1987-In Vitro

Chromosome Aberration 

Acceptable/Guideline

37.5, 50, 75, 125, 250, 

375, 500 μg/mL

40401010 NEGATIVE

There was no evidence that 

flurprimidol induced a clastogenic 

effect in the presence or absence of 

S9-activation.

870.5550 1982-Unscheduled DNA 

Synthesis

Acceptable/Guideline

0.5, 1, 5, 10, 50, 100, 

500, 1000 nmol/mL

00117938 NEGATIVE

There was no evidence that 

unscheduled DNA synthesis, as 

determined by radioactive tracer 

procedures (nuclear silver grain 

counts) was induced

870.5915 1982-In Vivo Sister 

Chromatid Exchange

Acceptable/Guideline

50, 100, 200, 300 

mg/kg

00117937 NEGATIVE
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

There was no concentration-related 

positive response of SCE induced 

over background.

870.6200a Acute Neurotoxicity

Acceptable/Nonguideline

70, 285, and 500 mg/kg 48897501 NOAEL = 70 mg/kg/day

LOAEL = 285 mg/kg/day based on 

based on treatment related findings 

at the mid-dose included gait 

abnormality in both sexes, low 

arousal and impaired righting reflex 

in males, and hunched body in 

females, 7-8 hours after dosing. 

870.6200b Sub-Chronic 

Neurotoxicity

Acceptable/Nonguideline

0, 8, 43, 73 mg/kg/day 49167101 NOAEL = 77 mg/kg/day

No effects observed. 

870.7485 1987-Metabolism and 

Pharmacokinetics-rat

Acceptable/Guideline

mg/kg/day =

2.5, 50

40184408

-

40184412, 

40401002, 

and 

40401003

Absorption was rapid (beginning 

within an hour of administration) 

and extensive (>80% dose). 

Excretion of the administered dose 

was nearly complete (>82% dose) 

within 7 days, and was recovered 

predominantly in the urine (53-75% 

dose), but also in the feces (17-34% 

dose). At 7 days post-dose, the liver 

contained a mean value of 0.1% of

the administered dose; all other 

tissues contained <0.1%. 

Consequently, bioaccumulation is 

not expected to occur. The terminal 

half-life of radioactivity in plasma is 

31-32 hours in males and 41-42 

hours in females at both doses. In 

general, the highest tissue 

concentrations of radioactivity were 

found in the adrenals, liver, and 

kidney. Unchanged parent was 

present in the feces in minor 

amounts <2.5% dose, as the parent 

was extensively degraded into over 

30 metabolites. The primary 

metabolite was identified (βhydroxy-α-methyl-β-[4-(trifluoromethoxy)phenyl]-5-

pyrimidinepropanoic acid) and was 

present at 10-20% dose, mainly in 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Flurprimidol

Guideline Study Type Dose Levels MRID Results

the urine. Other metabolites 

individually accounted for less than 

6% of the dose. Eleven of these 

metabolites were tentatively 

identified. Major metabolic 

pathways include oxidation of the 

isopropyl group and the pyrimidine 

ring. Oxidation of the carbinolcarbon atom and dehydration 

between the carbinol-carbon atom 

and isopropyl group were also 

observed. The absorption, 

distribution, excretion, or metabolite 

profiles were not dependent on sex, 

dose concentration, or the number of 

doses received.

870.7800 Immunotoxicity 10, 56, 95 mg/kg/day 49167201 NOAEL = 95 mg/kg/day

Nonguideline1987-Dermal 

Penetration-Monkey

Unacceptable/Nonguideline

mg/kg/day =

1.0

40184413 Dermal absorption rate not 

determined

A.3 Hazard Identification and Endpoint Selection

3.1 Acute Reference Dose (aRfD) (General Population)

Study Selected: Acute Neurotoxicity Study in Rats

MRIDs: 48897501

Dose and Endpoint for Risk Assessment: NOAEL= 70 mg/kg/day based on based on 

treatment related findings at the mid-dose included gait abnormality in both sexes, low arousal 

and impaired righting reflex in males, and hunched body in females, 7-8 hours after dosing at 

LOAEL of 285 mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: This study is considered to be the most 

appropriate for acute dietary dose and endpoint selection. No other studies in the database were 

available which contained acute effects relevant to the general population.

Acute RfD = 

100( )

70mg/kg/day

UF

= 0.7 mg/kg/day
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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A.3.2 Acute Reference Dose (aRfD) (Females 13-49 years old)

Study Selected: Developmental Toxicity in rats

MRIDs: 00147301

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg/day based on increased 

incidences of skeletal anomalies in the vertebrae (extra) and ribs (extra, rudimentary, cervical) at 

a LOAEL of 45 mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: This study is considered to be the most 

appropriate for acute dietary dose and endpoint selection. Skeletal abnormalities could be from a 

single exposure during pregnancy and are therefore considered a potential acute effect, and 

therefore, appropriate for the acute dietary endpoint scenario for females of child-bearing age. 

Acute RfD = 

100( )

10mg/kg/day

UF

= 0.1 mg/kg/day

A.3.3 Chronic Reference Dose (cRfD) 

Study Selected: Chronic Toxicity Study in Rats

MRIDs: 40486002

Dose and Endpoint for Risk Assessment: NOAEL= 3.6 mg/kg/day based on increased 

incidences of focal atypia, fatty change, and hepatocellular eosinophilic change in the liver of 

males at a LOAEL of 12.1 mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)

Comments on Study/Endpoint/Uncertainty Factors: The chronic toxicity study in rats is 

appropriate for both the population of concern (adults) and the duration of exposure. 

Chronic RfD = 

100( )

3.6mg/kg/day

UF

= 0.04 mg/kg/day

A.3.4 Incidental Oral Exposure (Short-term, 1-30 days)

Study Selected: 2-Generation Reproduction Toxicity Study in Rats

MRIDs: 00162770

Dose and Endpoint for Risk Assessment: Offspring NOAEL= 7.3 mg/kg/day based on 

decreased survival and body weights (20-39%) in the pups at the LOAEL of 74 mg/kg/day.

Uncertainty Factor: 100x (10x interspecies extrapolation, 10x intraspecies variability, 1x FQPA 

Safety Factor)
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Comments on Study/Endpoint/Uncertainty Factors: The endpoint of concern in this study is 

appropriate for the population (infant and children) and the duration of concern.

A.3.5 Dermal Exposure (Short-, Intermediate-Term)

A dermal assessment is not required for the flurprimidol. No toxicity was observed up to the 

limit dose in the dermal toxicity study. No quantitative susceptibility was observed in any study. 

Qualitative susceptibility was observed in the rat developmental study, however; as the effects 

occurred in the presence of decreased maternal body weights the available dermal toxicity study 

is considered to be protective as no decreased body weights were observed. Additionally, using 

the estimated upper bound dermal absorption value would result in a dermal LOAEL near the 

limit dose (~750 mg/kg/day). 

A.3.6 Inhalation Exposure (Short-, and Intermediate-Term)

Study Selected: 13-Week Inhalation Toxicity Study in Rats

MRIDs: 49007301, 49007302

Dose and Endpoint for Risk Assessment: NOAEL= 0.1 mg/L based on results in the rangefinding study (MRID 49007302) where goblet cell hyperplasia was observed in nasal level II, III, 

IV, V, and VI of male rats (nasal passages of females were not examined microscopically) at a 

LOAEL of 0.4 mg/L. 

Comments on Study/Endpoint/Uncertainty Factors: The inhalation toxicity study was chosen 

as it is a route-specific study and appropriate for the duration of concern. Long-term inhalation 

assessment is not required because this exposure length is not expected based on current use 

patterns.
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Appendix B. DEEM-FCID Model Inputs and Outputs for Acute and Chronic Dietary 

Exposure Estimates.

Acute DW Analysis- DEEM Input File

US EPA Ver. 3.18, 03-08-d

DEEM-FCID Acute analysis for FLURPRIMIDOL

Residue file name: 

C:\Users\spiper\Documents\DEEM_version316\Flurprimidol\Flurprimidol_acute.r08

Analysis Date 03-19-2015 Residue file dated: 03-19-2015/09:05:27

Reference dose: aRfD = 0.7 mg/kg bw/day NOEL = 70 mg/kg bw/day

Comment: Drinking Water Assessment Only

----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

Code Grp Food Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

8601000000 86A Water, direct, all sources 0.707000 1.000 1.000

8602000000 86B Water, indirect, all sources 0.707000 1.000 1.000

Acute DW Analysis- DEEM Output File

US EPA Ver. 3.18, 03-08-d

DEEM-FCID ACUTE Analysis for FLURPRIMIDOL NHANES 2003-2008 2-Day

Residue file: Flurprimidol_acute.r08 Adjustment factor #2 NOT used.

Analysis Date: 03-19-2015/09:08:56 Residue file dated: 03-19-2015/09:05:27

NOEL (Acute) = 70.000000 mg/kg body-wt/day

Acute Pop Adjusted Dose (aPAD) varies with population; see individual reports

RAC/FF intake summed over 24 hours

Run Comment: "Drinking Water Assessment Only"

=====================================================================

==========

Summary calculations--per capita:

--- 95th Percentile---- --- 99th Percentile---- ---99.9th Percentile----

Exposure % aPAD MOE Exposure % aPAD MOE Exposure % aPAD MOE 

---------- ------- -------- ---------- ------- -------- ---------- ------- --------

Total US Population:

 0.038551 5.51 1815 0.063571 9.08 1101 0.120761 17.25 579 

All Infants:

 0.120747 17.25 579 0.163551 23.36 428 0.239703 34.24 292 

Children 1-2:

 0.059446 8.49 1177 0.089514 12.79 781 0.220448 31.49 317 

Children 3-5:

 0.048236 6.89 1451 0.073875 10.55 947 0.118579 16.94 590 
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

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Children 6-12:

 0.036856 5.27 1899 0.060486 8.64 1157 0.093227 13.32 750 

Youth 13-19:

 0.032105 4.59 2180 0.052878 7.55 1323 0.079837 11.41 876 

Adults 20-49:

 0.037936 5.42 1845 0.056455 8.07 1239 0.082132 11.73 852 

Adults 50-99:

 0.033793 4.83 2071 0.051239 7.32 1366 0.080769 11.54 866 

Female 13-49:

 0.038477 38.48 1819 0.056580 56.58 1237 0.079349 79.35 882 

Chronic DW Analysis- DEEM Input File

US EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for FLURPRIMIDOL

Residue file: 

C:\Users\spiper\Documents\DEEM_version316\Flurprimidol\Flurprimidol_chronic.r08

 Adjust. #2 NOT used

Analysis Date 03-19-2015 Residue file dated: 03-19-2015/09:11:33

Reference dose (RfD) = 0.04 mg/kg bw/day

Comment:Drinking Water Assessment Only

----------------------------------------------------------------------------------

Food Crop Residue Adj.Factors

EPA Code Grp Food Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------

8601000000 86A Water, direct, all sources 0.656000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.656000 1.000 1.000 

Chronic DW Analysis- DEEM Output File

US EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for FLURPRIMIDOL NHANES 2003-2008 2-day

Residue file name: 

C:\Users\spiper\Documents\DEEM_version316\Flurprimidol\Flurprimidol_chronic.r08

 Adjustment factor #2 NOT used.

Analysis Date 03-19-2015/09:13:57 Residue file dated: 03-19-2015/09:11:33

Reference dose (RfD, Chronic) = .04 mg/kg bw/day

COMMENT 1: Drinking Water Assessment Only

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 Total exposure by population subgroup

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 Total Exposure
Flurprimidol Human Health Draft Risk Assessment DP No. D427106

Page 48 of 48

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 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

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Total US Population 0.013736 34.3%

Hispanic 0.013115 32.8%

Non-Hisp-White 0.014128 35.3%

Non-Hisp-Black 0.011334 28.3%

Non-Hisp-Other 0.015832 39.6%

Nursing Infants 0.012427 31.1%

Non-Nursing Infants 0.045687 114.2%

Female 13+ PREG 0.012934 32.3%

Children 1-6 0.017593 44.0%

Children 7-12 0.011452 28.6%

Male 13-19 0.009442 23.6%

Female 13-19/NP 0.010581 26.5%

Male 20+ 0.012797 32.0%

Female 20+/NP 0.014427 36.1%

Seniors 55+ 0.013281 33.2%

All Infants 0.035418 88.5%

Female 13-50 0.013670 34.2%

Children 1-2 0.019815 49.5%

Children 3-5 0.016695 41.7%

Children 6-12 0.012040 30.1%

Youth 13-19 0.010017 25.0%

Adults 20-49 0.013705 34.3%

Adults 50-99 0.013548 33.9%

Female 13-49 0.013654 34.1%

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