Date: 

Subj ect: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

January 6, 2016 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Fluridonc. Occupational and Residential Exposure Assessment for Registration 

Review and to Support the Registration of a Proposed Use on Cotton. 

PC Code: I 12900 

Decision No.: 494948 

Petition No.: 4F8308 

OP Barcodc: 0431020 

Registration No.: 67690-NEW 

Regulatory Action: Reg. 

Review/Section 3 

Ris k Assessment Type: Occupational/Residential Exposure Assessment 

TXR No.: NA 

Case No.: 7200 

CAS No.: 59756-60-4 

MRID No.: NA 40 CFR: 180.420 

From: 

Through: 

To: 

('\ 

Alexandra Gavelek, Biologist \~ ~ l ~ 

Ri

Kelly 

sk Assessment 

M. Lowe, E

Branch 

nvironment

YN

a

JJ 

l Scientist j~ 

0 ~ 

Health Effects Division (7509P) 

M ich.ael Metzger, Branch Chief/ j J () / f j\ ______----

Risk Assessment Branch YNII ~v1\td~ - fl er 

Health Effects Division (7509P) 

and 

Barry O'Keefe, Biologist ~ ~ , 

Exposure 

Bridgett Bobowiec, 

Science Advisory 

Biologist 

Committee 

~ 

(ExpoSAC) 

~ 

I HED 

SaraJ1 Meadows, Risk Manager Reviewer 

Kathryn Montague, Risk Manager 

Registration Division 

And 

Leigh Rimmer, Chemical Review Manager 

Tom Myers, Team Leader 

Kevin Costello, Branch Chief 

Pesticide Re-Evaluation Division 

Page I of 37 
Introduction 

The Pesticide Re-evaluation Division (PRO) requested that the Health Effects Division (HED) 

conduct an occupational exposure/risk assessment for the registered uses of fluridone as part of 

Registration Review. This memorandum contains HED's occupational/residential exposure and 

risk assessment required during Registration Review to reflect the updated science policies and 

procedures. 

In addition, the Registration Division (RD) requested that HED conduct an exposure and risk 

assessment for the proposed new use of fluridone on cotton. Therefore, this exposure assessment 

also incorporates the proposed new use on cotton. 

It is HED policy to use the best ~vailable data to assess exposure. Several sources of generic 

data were used in this assessment as surrogate data in the absence of chemical-specific data, 

including Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1 ); the Agricultural 

Handler Exposure Task Force (AHETF) database; and the Agricultural Reentry Task Force 

(ARTF) database. Some of these data are proprietary, and subj ect to the data protection 

provisions of the Federal lnsecticide, Fungicide, and Rodenticide Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on June 4, 2015. 

Page 2 of37 
Page 3 of 37

Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 Risk Assessment Conclusions and Recommendations........................................................ 6

2.1 Summary of Risk Estimates............................................................................................. 6

2.2 Label Recommendations.................................................................................................. 7

2.3 Data Deficiencies and Requirements ............................................................................... 7

3.0 Hazard Characterization....................................................................................................... 7

4.0 Use Profile ........................................................................................................................... 8

5.0 Residential Exposure and Risk Estimates............................................................................ 9

5.1 Residential Handler Exposure/Risk Estimates............................................................... 10

5.2 Residential Post-application Exposure/Risk Estimates.................................................. 13

5.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 14

5.4 Non-occupational Exposures and Risk Estimates from Spray Drift.............................. 14

5.5 Non-occupational Bystander Post-Application Inhalation Exposure............................. 16

6.0 Occupational Exposure and Risk Estimates ...................................................................... 16

6.1 Occupational Handler Exposure/Risk Estimates............................................................ 16

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

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 23

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 23

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms..................... 25
Page 4 of 37

1.0 Executive Summary

Fluridone (l-methyl-3-phenyl-5-[3-(trifluoromethyl) phenyl]-4(lH)-pyridinone) is registered in 

end-use formulations as a selective systemic aquatic herbicide for management of aquatic 

vegetation in fresh water ponds, lakes, reservoirs, drainage canals, and irrigation canals, 

including dry or dewatered areas of these sites; in dry canals; and for homeowner use in ponds. 

There is also a newly proposed use of fluridone on pre-plant or pre-emergent cotton. 

The end-use products registered for use in aquatic settings are formulated as liquids, granulars, 

and water dispersible granulars (WDGs). In aquatic settings, fluridone can be applied: (1) via 

aerial, boom or handheld applications to ponds/lakes at a maximum application rate of 0.4 lb 

ai/A-ft; (2) via direct metering to moving water at a maximum rate of 0.11 lb ai/A-ft; (3) via 

handheld equipment to static canals at a maximum rate of 2 lb ai/A; and (4) via open pour to 

residential ponds at a maximum rate of 0.12 lb ai/A-ft. The proposed use on cotton is for a liquid 

formulation to be applied via groundboom equipment at a maximum rate of 0.3 lb ai/A. The 

proposed product label for the pre-emergent cotton use directs applicators and other handlers to 

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

eyewear. The registered product labels for the aquatic uses do not require specific clothing or 

any personal protective equipment (PPE). The restricted entry interval (REI) on the proposed 

label for cotton is 24 hours. The aquatic labels do not include a REI statement. 

For both the proposed and registered uses, occupational handler exposures are anticipated. 

Occupational post-application exposures are not anticipated since (1) the proposed cotton use is 

pre-plant or pre-emergent, and (2) occupational post-application activities are not anticipated 

after the use of fluridone in aquatic environments. Residential handler (adults) and postapplication exposures (adults and children 3 to <6 years old) are anticipated from the registered 

aquatic uses. Non-occupational spray drift exposures have also been assessed as part of 

Registration Review for adults and children (1 to <2 years old). 

Fluridone has low to moderate acute oral, inhalation and dermal toxicity. Fluridone is not 

irritating to skin and it is not a skin sensitizer, but is a moderate irritant to the eyes. In the 

carcinogenicity study in mice, toxicity was limited to liver and manifested as changes in a liver 

enzyme and histopathology. A point of departure (POD) of 15 mg/kg/day was used to assess all 

routes (dermal, inhalation, and incidental oral). The level of concern (LOC) for fluridone 

exposures is a margin of exposure (MOE) of 100 (10x interspecies extrapolation and 10x 

intraspecies extrapolation). Based on the lack of evidence for carcinogenicity in these studies 

(mice and rats), fluridone is classified as Group E Carcinogen -Evidence of Non-Carcinogenicity 

for Humans”. 

Another aqueous photoproduct found in laboratory studies, N-methylformamide (NMF), is more 

toxic than the parent compound and requires a separate assessment (Dole, 2004, D306456). 

According to the Environmental Fate and Effects Division (EFED), NMF remains a residue of 

concern unless acceptable aqueous photolysis data are submitted (Orrick; 2015, D423846). A 

separate assessment for NMF is provided in Appendix B of this memo.
Page 5 of 37

The residential handler assessment assessed dermal and inhalation exposure to homeowners 

applying fluridone to ponds; there were no risks of concern for residential handlers (i.e., all 

combined MOEs ≥ 100). The residential post-application exposure assessment assessed adults 

and children (3 to <6 years old) who may be exposed fluridone while swimming in treated water

(dermal, inhalation and incidental ingestion exposure routes). There were no risks of concern for 

swimmers (i.e., all combined MOEs ≥ 100 for fluridone).

There is potential non-occupational exposure via spray drift from the proposed agricultural use 

on cotton. The spray drift assessment assessed adults and children (1 to <2 years old) who may 

be exposed to residues of fluridone on a adjacent lawn next to a field that was previously treated 

with fluridone. There were no risks of concern for exposures from spray drift (dermal and 

incidental oral MOEs ≥ 100 at the edge of the field).

Occupational handlers may be exposed via dermal and inhalation routes while applying the 

products to aquatic areas or to cotton. There were no risks of concern (i.e., all MOEs ≥ 100) for 

occupational handlers making applications to cotton via groundboom equipment with the 

proposed label-required clothing (i.e. no gloves or respirator). For aquatic use applications, most 

scenarios do not have risk estimates of concern with baseline clothing and no gloves or respirator

except for some of the handheld equipment scenarios. For these scenarios, additional PPE (e.g., 

gloves and/or a double layer of clothing) are required to reach acceptable MOEs. Although 

aquatic applications do not fall under the purview of the Worker Protection Standard (WPS), 

product labeling should direct applicators to wear long-sleeved shirt and long pants and shoes 

plus socks. Because of the risk concerns identified in the occupational handler assessment, it is 

recommended that the product labeling for aquatic uses require handlers to wear additional PPE. 

As the proposed use is on pre-plant or pre-emergent cotton, no occupational post-application 

dermal exposure to residues on foliage is expected. The REI of 24 hours on the proposed label 

for the cotton use is adequate and meets the minimum WPS requirements. For the currently 

registered uses of fluridone in aquatic environments, there are no occupational post-application 

activities which would result in occupational exposures from treated bodies of water. As 

applications to aquatic areas do not fall under the purview of WPS and re-entry exposure is 

considered to be negligible, an REI is not applicable for these uses.

Based on the Agency’s current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for fluridone at this time. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for fluridone.

Human Studies Review

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

intentionally exposed to a pesticide or other chemical. These data, which include PHED 1.1; the 

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

ARTF database; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that 

review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics 
Page 6 of 37

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

sources, as well as guidance on their use, can be found at the Agency website1. 

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

Proposed Cotton Use:

 There are no risk estimates of concern for adults or children (1 to <2 years old) exposed 

to fluridone via spray drift from the cotton use (MOEs ≥ 1,800 for adults and 880 for 

children at the field edge; LOC = 100). 

 Occupational handler combined dermal and inhalation MOEs range from 230 to 640 with 

baseline clothing (long sleeved shirt, long pants, shoes plus socks, no gloves, and no 

respirator for all scenarios except aerial applicator where engineering controls were 

used). The proposed product label for the pre-emergent cotton use directs applicators and 

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

plus socks and protective eyewear. 

 As the proposed use is on pre-plant or pre-emergent cotton, no occupational postapplication dermal exposure to residues on foliage is expected. The REI of 24 hours on 

the proposed label for the cotton use is adequate and meets the minimum WPS 

requirements. 

Registered Aquatic Uses:

 There are no risk estimates of concern for residential handlers applying ready-to-use 

(RTU) products to ponds (MOEs ≥ 2,000; LOC = 100). 

 There are no risk estimates of concern to adults or children (3 to <6 years old) swimming 

in water that was treated with fluridone.

o For fluridone, combined (dermal + inhalation + incidental ingestion) exposures 

resulted in MOEs ≥ 52,000 for adults and 12,000 for children (3 to <6 years old); 

LOC = 100. 

 Occupational handler combined dermal and inhalation MOEs range from 6.1 to 18,000 

with baseline clothing (single layer clothing, shoes plus socks, no gloves, and no 

respirator for all scenarios except aerial applicator where engineering controls were 

used). 

o The registered product labels for aquatic uses do not require any PPE. The 

scenario of mixing/loading/applying product with handwand sprayer to aquatic 

sites was not of concern with the addition of gloves. The scenario of 

mixing/loading/applying product with backpack sprayer to aquatic sites was not 

of concern with the addition of double layer clothing and gloves.

 Since the currently registered uses of fluridone are in aquatic environments, there are no 

occupational post-application activities which would result in occupational exposures 

from treated bodies of water. As application to aquatic areas do not fall under the 

purview of WPS and re-entry exposure is considered to be negligible, an REI is not 

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 7 of 37

applicable for these uses.

2.2 Label Recommendations 

Proposed Cotton Use:

No label recommendations.

Registered Aquatic Use:

Although aquatic applications do not fall under the purview of the Worker Protection Standard 

(WPS), HED recommends that product labeling direct applicators to wear long-sleeved shirt and 

long pants and shoes plus socks. Because of the risk concerns identified in the occupational 

handler assessment, it is recommended that the product labeling for aquatic uses require handlers

to wear additional PPE. 

2.3 Data Deficiencies and Requirements

None.

3.0 Hazard Characterization

Fluridone has low to moderate acute oral, inhalation and dermal toxicity. Fluridone is not 

irritating to skin and it is not a skin sensitizer, but is a moderate irritant to the eyes. 

Table 3.0.1 – Acute Toxicity Categories for Fluridone

Study Results Tox Category

Acute Oral (870.1100) LD50 > 10000 mg/kg IV

Acute Dermal (870.1200) LD50 > 2000 mg/kg III

Acute Inhalation (870.1300) LC50 > 2.13 mg/L IV

Primary Eye Irritation (870.2400) Moderate effects III

Primary Skin Irritation (870.2500) No dermal effects IV

Dermal Sensitization (870.2600) Not sensitizing N/A

Toxicological PODs Used for Risk Assessment

The subchronic neurotoxicity study has been waived by the HED Hazard and Science Policy 

Committee (HASPOC) (TXR# 0056853, 12/20/13) and the subchronic inhalation toxicity study 

has been waived by HASPOC (TXR# 0057221, 05/14/15).

In the carcinogenicity study in mice, toxicity was limited to liver and manifested as changes in a 

liver enzyme and histopathology. A point of departure (POD) of 15 mg/kg/day was used to 

assess all routes (dermal, inhalation, and incidental oral). The level of concern (LOC) for 

fluridone exposures is a margin of exposure (MOE) of 100 (10x interspecies extrapolation and 

10x intraspecies extrapolation). Based on the lack of evidence for carcinogenicity in these 

studies (mice and rats), fluridone is classified as Group E Carcinogen -Evidence of NonCarcinogenicity for Humans”. 
Page 8 of 37

Table 3.0.2. Summary of Toxicological Doses and Endpoints for Fluridone for Use in Residential and Occupational 

Human Health Risk Assessments 

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Study and Toxicological Effects

Dermal 

Short- and 

IntermediateTerm

NOAEL = 15 

mg/kg/day

39% DAF

UFA= 10x

UFH=10x

FQPA SF = 1x

2 yr cancer study in mice 

LOAEL =50 mg/kg/day based on increased alkaline phosphatase 

activity and increased incidence of hepatocellular hyperplasia

Inhalation Shortand Intermediate 

Term

NOAEL = 15 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 1x

2 yr cancer study in mice 

LOAEL =50 mg/kg/day based on increased alkaline phosphatase 

activity and increased incidence of hepatocellular hyperplasia

Incidental Oral

Short- and 

IntermediateTerm exposures

NOAEL = 15 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 1x

2 yr cancer study in mice 

LOAEL =50 mg/kg/day based on increased alkaline phosphatase 

activity and increased incidence of hepatocellular hyperplasia

Cancer (dermal 

and inhalation)

Fluridone is classified as “not likely” as a human carcinogen. Quantitative cancer risk assessment is not 

required.

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

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. 

LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. FQPA SF = Food Quality 

Protection Act Safety Factor.

Absorption

A dermal absorption factor of 39% was used for the fluridone exposure assessment. This factor 

is estimated from the ratios of LOAELs from a 21-day dermal toxicity study and a 

developmental toxicity study in rabbits. Since no inhalation absorption data are available, 

toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral 

route of exposure.

Body Weight

The standard body weight for the general population (80 kg) was used for all fluridone exposure 

scenarios covered in this risk assessment since the endpoints selected were not developmental 

and/or fetal effects. For the child swimmer exposure assessments, the 3 to < 6 year old body 

weight of 19 kg is appropriate. A body weight of 11 kg was used to assess exposure to children 

(1 to <2 years old) from spray drift.

4.0 Use Profile 

Proposed Use on Cotton

Table 4.1.1 provides a summary of the proposed cotton use. The proposed use is for a liquid 

formulation to be applied via groundboom equipment at a maximum rate of 0.3 lb ai/A. The 

proposed product label for the pre-emergent cotton use directs applicators and other handlers to 

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

eyewear. The restricted entry interval (REI) on the proposed label for cotton is 24 hours. 

Registered Aquatic Uses

Table 4.1.2 provides a summary of the registered aquatic uses of fluridone. The end-use 

products registered for use in aquatic settings are formulated as liquids, granulars, and water 

dispersible granulars (WDGs). In aquatic settings, fluridone can be applied: (1) via aerial, boom 

or handheld applications to ponds/lakes at a maximum application rate of 0.4 lb ai/A-ft; (2) via 

direct metering to moving water at a maximum rate of 0.11 lb ai/A-ft; (3) via handheld 
Page 9 of 37

equipment to static canals at a maximum rate of 2 lb ai/A; and (4) via open pour to residential 

ponds at a maximum rate of 0.12 lb ai/A-ft. The registered product labels for the aquatic uses 

do not require specific clothing or any personal protective equipment (PPE). The aquatic labels 

do not include a REI statement. 

Table 4.1.1. Summary of Directions for the Proposed Use of Fluridone on Cotton.

EPA Reg. No. Formulation Max. Applic. Rate Rate Calculation; Application 

Directions

67690-TG

SP1621 Herbicide 

Liquid concentrate

17.26% fluridone 

(1.6 lb fluridone/gal)

1.5 pints per acre per year (0.3 lb 

ai/acre)

Pre-plant or pre-emergent application

One application

Do not apply by air or chemigation

Table 4.1.2. Summary of Directions for the Registered Use of Fluridone in Aquatic Sites.

EPA Reg. No. Formulation Max. Applic. Rate Rate Calculation; Application 

Directions

Registered Aquatic Uses

8959-58, 61842-29, 

67690-3, 67690-12, 

67690-21, 67690-32, 

67690-45, 81927-50

Granular/ WDG, 

5% ai

(0.05 lb ai/lb)

90 ppb in ponds, 150 ppb in 

lakes and reservoirs

90 ppb: 5 lb / acre-foot = 0.25 lb ai/acrefoot

150 ppb: 8.1 lb /acre-foot = 0.4 lb ai/acrefoot

Static/dry canals: 40 lbs 

product/acre 2 lb ai/surface acre

Moving water: maintain 

concentration of up to 40 ppb 40 ppb: 0.11 lb ai/acre-foot

67690-61

Solid, 2.7% ai

(0.027 lb ai/lb)

90 ppb in ponds, 150 ppb in 

lakes and reservoirs

90 ppb: 9 lb/ acre-foot = 0.24 lb ai/acrefoot

150 ppb: 15 lb / acre-foot = 0.4 lb ai/acrefoot 

8959-57, 61842-11, 

67690-4, 67690-30, 

81927-45

Liquid Concentrate, 

41.7% ai

(4 lb ai/gallon)

90 ppb in ponds, 150 ppb in 

lakes and reservoirs

90 ppb: 7.7 fl oz / acre-foot = 0.24 lb 

ai/acre-foot

150 ppb: 13 fl oz / acre-foot = 0.4 lb 

ai/acre-foot

Static/dry canals: 2 qts/acre 2 qts/acre = 2 lb ai/acre

Moving water: maintain 

concentration of up to 40 ppb 40 ppb: 0.11 lb ai/acre-foot

67690-54

Liquid Concentrate, 

6.3% ai 

(0.5 lb ai/gallon)

90 ppb in ponds, 150 ppb in 

lakes and reservoirs

90 ppb: 0.48 gal/ acre-foot = 0.24 lb 

ai/acre-foot

150 ppb: 0.81 gal/ acre-foot = 0.4 lb ai/ 

acre-foot

8959-59, 61842-28, 

67690-48, 81927-51

Ready-to-use, 

3.79% ai

(0.08 lb ai/qt)

Aquatic weeds in Ponds: 1 

qt/acre-foot

Watermeal in ponds: 1.5 

qts/acre-foot

3 qts/acre-foot/season

Aquatic weed: 1 qt/acre-foot = 0.08 lb 

ai/acre-foot

Watermeal: 1.5 qt/acre-foot

= 0.12 lb ai/acre-foot

5.0 Residential Exposure and Risk Estimates

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

that have been reassessed in this document for Registration Review. The registered aquatic uses 
Page 10 of 37

have been assessed according to HED’s November 2015 Draft Aquatic Use SOP. The revision 

of residential exposures will impact the human health aggregate risk assessment for fluridone.

5.1 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 ready-to-use (RTU) aquatic products registered for fluridone state that “unless the pond is 

privately owned by the applicator, prior to application, consult with appropriate state or local 

water authorities.” Therefore, it is assumed that this type of product can be applied by the 

homeowner to their privately owned pond. The quantitative exposure/risk assessment developed 

for residential handlers is based on the following scenario: 

 Ready-to-use (RTU) aquatic applications

Residential Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Each assumption and factor is detailed below.

Application Rate: The maximum rate for residential use from Table 4.1.2 was used; 0.12 lb 

ai/acre-foot = 0.00000275 lb ai/ft3.

Unit Exposures and Area Treated or Amount Handled:

Unit exposure values to represent a homeowner pouring a RTU formulation have been adjusted 

from the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table2”, which, 

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

of the various sources, can be found at the Agency website3. The occupational unit exposure 

(representing long-sleeved shirt, long pants, and no gloves) has been adjusted to represent a 

homeowner wearing a short-sleeved shirt and shorts. Estimates for area treated or amount 

handled were taken from HED’s Draft November 2015 Aquatic Use SOP. 

Exposure Duration: 

Residential handler exposure is expected to be short-term in duration. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners.

Residential Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate exposure and dose for residential handlers can be found in 

Appendix A and/or the 2012 Residential SOPs4and/or the draft November 2015 Aquatic Use 

SOP.

 

2 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

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

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 11 of 37

Combining Exposures/Risk Estimates:

Dermal and inhalation risk estimates were combined in this assessment, since the toxicological 

effects for these exposure routes were the same. Dermal and inhalation risk estimates were 

combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined Dermal + Inhalation dose (mg/kg/day)

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

Residential handler combined dermal and inhalation MOEs range from 1,800 to 1,400,000. 

Since the MOEs are greater than the LOC of 100, there are no risk estimates of concern for 

residential handlers. 
Page 12 of 37

Table 5.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Fluridone.

Exposure Scenario Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)1

Inhalation 

Unit Exposure 

(mg/lb ai)1

Maximum 

Application 

Rate2

Area Treated or 

Amount Handled 

Daily3

Dermal Inhalation Combined

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE

(LOC = 100)8

Mixer/Loader/Applicator

Ready-to-use – Open Pour 

to Recreational Ponds 100 0.232 0.219 0.12 lb ai/acrefoot

2.5 acres, 7 foot 

depth 0.0024 6,300 0.0057 2,600 1,800

Ready-to-use – Open Pour 

to Ornamental Ponds 100 0.232 0.219 0.00000275 lb ai/ft3

500 ft2, 2 foot 

depth 0.0000031 4,800,000 0.0000075 2,000,000 1,400,000

1 Unit exposure values based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2015) adjusted for difference in clothing (short-sleeved shirt and short 

pants vs long-sleeved shirt and long pants).

2. Based on registered labels.

3 Based on HED’s Draft November 2015 Aquatic SOP.

4 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre-ft or lb ai/ft3) × Area Treated or Amount Handled (A-ft/day or ft3/day) × Dermal Absorption Factor (39%) ÷ Body 

Weight (80 kg).

5 Dermal MOE = Dermal NOAEL (15 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre-ft or lb ai/ft3) × Area Treated or Amount Handled (A-ft/day or ft3/day) ÷ Body Weight (80 kg).

7 Inhalation MOE = Inhalation NOAEL (15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (15 mg/kg/day) ÷ (Dermal Dose + Inhalation Dose).
Page 13 of 37

5.2 Residential Post-application Exposure/Risk Estimates

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

an environment that has been previously treated with fluridone. The recreational swimmer has 

the potential for exposure to fluridone in treated water, as well as the degradate NMF which is 

formed in water. The quantitative exposure/risk assessment for residential post-application 

exposures is based on the following scenarios: 

 Adults and children (3 to <6 years old) swimming in treated water (dermal, inhalation

and incidental ingestion)

Residential Post-application Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. Each assumption and factor is detailed in the Draft 2015

Aquatic Use SOP.

Application Rate:

As was done in the previous assessments, the maximum label rate of 150 ppb (0.15 mg/L) was 

used to assess aquatic exposure of fluridone. 

Exposure Duration: 

Residential exposure is expected to be short-term in duration. 

Residential Post-application Non-Cancer Exposure and Risk Equations

The algorithms used to estimate residential post-application exposure and dose can be found in 

Appendix A and/or the Draft November 2015 Aquatic Use SOP.

Combining Exposure and Risk Estimates

Since dermal, inhalation and incidental oral exposure routes share a common toxicological 

endpoint, exposure estimates have been combined for those routes. 

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

For fluridone, the combined MOE for adults swimmers is 52,000 and for child swimmers is 

12,000; therefore, there are no risk estimates of concern (LOC = 100). 

Table 5.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for Fluridone.

Lifestage

Post-application Exposure 

Scenario Application 

Rate1

Dose 

(mg/kg/day)2

MOEs

(LOC = 100)3

Combined Routes

(X indicates 

Combined)

Combined MOEs

(LOC = 100) Use Site Route of 

Exposure

Adult

Aquatic

Dermal

150 ppb

(0.15 mg/L)

0.00028 54,000 X

52,000 Inhalation 4.05E-08 370,000,000 X

Incidental 

Ingestion 0.0000094 1,600,000 X

Child (3 to 

<6 years 

old)

Dermal 0.00114 13,000 X

12,000 Inhalation 2.8E-7 54,000,000 X

Incidental 

Ingestion 9.87E-5 150,000 X

1 Based on registered labels.
Page 14 of 37

2 Dose (mg/kg/day) equations provided in Appendix A.

3 MOE = POD (15 mg/kg/day) ÷ Dose (mg/kg/day).

4 Combined MOE = 1 ÷ (1/dermal MOE) + (1/inhalation MOE) + (1/incidental oral MOE), where applicable.

5.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 5.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for fluridone.

 The recommended residential exposure for use in the adult aggregate assessment reflects 

dermal and inhalation exposure from applications via pouring to recreational ponds.

 The recommended residential exposure for use in the child (3 to <6 years old) aggregate 

assessment reflects dermal, inhalation, and incidental oral exposures from postapplication exposure to aquatic applications.

Table 5.3.1. Recommendations for the Residential Exposures for the Fluridone Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Adult Handler –

RTU 0.0024 0.0057 N/A 0.0081 6,300 2,600 N/A 1,800

Child (3 to < 

6 years old) Swimming 0.00114 2.8E-7 9.9E-5 0.0012 13,000 54,000,000 150,000 12,000

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + incidental oral 

(where applicable).

2 MOE = the MOEs associated with the highest residential doses. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental 

Oral MOE), where applicable.

5.4 Non-occupational Exposures and Risk Estimates from 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 indirect 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 onto 50-feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

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

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.5 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, 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 indirect 

exposure, are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

 

5 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.
Page 15 of 37

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 fluridone. 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 and the 

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. 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 based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available.6 AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard 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. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. 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 5.4.1 provides the screening level drift-related risk estimates. 

5.4.1 Risk Estimates From Lawn Deposition Adjacent to Applications

Fluridone is a systemic herbicide, meaning its herbicidal mode of action requires it to be 

absorbed and translocated in the weeds. It is not a contact herbicide and thus the application 

method is not as a broadcast application meant to cover the surface area of the weeds. Foir the 

aquatic use applications, it is applied in a directed manner, usually using a hose, wand or meter, 

as a surface or subsurface application to water in order to maintain a specified herbicide 

concentration in the water body to control aquatic weeds systemically. The large/coarse droplet 

size and directed spray methods greatly reduce the spray drift potential for aquatic applications. 

As the application methods are not conducive to spray drift as described and assessed as part of 

the spray drift policy, a quantitative spray drift assessment is not required for the aquatic uses of 

the herbicide. 

The spray drift risk estimates for the proposed cotton use are based on an estimated deposited 

residue concentration, as a result of the screening level agricultural application scenarios. 

Fluridone is proposed for use on pre-emergent cotton and can be applied via groundboom. 

Aerial application is prohibited. The spray drift assessment was completed assuming the highest 

proposed single application rate to cotton of 0.3 lb ai/A. The recommended drift scenario 

screening level options are listed below: 

 

6http://www.agdrift.com/ 
Page 16 of 37

 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. 

The applicable LOC is 100, so MOEs < 100 would be of concern. Exposures were considered 

for 50 feet wide lawns where the nearest side of the property was directly adjoining the treated 

field (at field edge). Results are presented in Table 5.4.1; no risk estimates of concern were 

identified at field edge. 

Table 5.4.1. Adult and Children (1<2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for 

Fluridone 

Population and Exposure 

Route Application 

Method 

Spray Type/ Nozzle 

Configuration

Appl. Rate 

(lb ai/A)

TTR 

(μg/cm2)

a

MOE At 

Field Edge

(LOC = 100)

Cotton 

Adults – Dermal Groundboom High Boom Very fine to 

Fine

0.3 0.033

1,800

Children (1 to <2 years 

old) – Combined Dermal 

and Hand-to-mouth

Groundboom High Boom Very fine to 

Fine 880

a. TTR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.1 and D = 0.10 per day 

5.5 Non-occupational 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.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-

0037). The agency has evaluated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

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

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

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

fluridone.

6.0 Occupational Exposure and Risk Estimates

6.1 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. 
Page 17 of 37

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 and

proposed uses. The quantitative exposure/risk assessment developed for occupational handlers is 

based on the following scenarios: 

Proposed Cotton Use:

 Mix/load liquid for groundboom application to pre-emergent cotton

 Applying spray by groundboom application to pre-emergent cotton

Registered Aquatic Uses:

 Mix/load liquid for aerial/boom application or direct metering to lakes/canals

 Mix/load WDG/granule for aerial/boom application to lakes/canals

 Applying spray by aerial/boom application to aquatic area

 Applying granule by aerial/boom application to aquatic area

 Mixing/loading/applying with handheld equipment to aquatic areas (lakes/canals)

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate: 

Application rates are provided in Table 4.1.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data 

protection provisions of FIFRA. The standard values recommended for use in predicting handler 

exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table7”, which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website8.

Area Treated or Amount Handled: 

 For proposed cotton use (based on ExpoSAC Policy 9.1) : 200 acres for groundboom 

application to high-acreage crop

 For registered aquatic uses: area treated assumption (30 acres) is based on information 

from the Army Corp of Engineers (endothall reregistration eligibility decision (RED), 

D319373, 8/12/05; 2,4-D RED, D316596, 5/4/05). The depth of 7 feet is assumed to be 

consistent with the EFED farm pond model. For application to aquatic sites with 

handheld equipment, it is assume the area treated is 5 acres of surface area and a depth of 

1 foot. For static canals, the area treated is assumed to be a canal 1 mile long and 20 ft 

 

7 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 18 of 37

wide (2.5 acres). For assessing flowing water, it is assumed that the upper end of the 

flow rate is 200 cubic feet/second (endothall RED, D319373, 8/12/05). This is equivalent 

to approximately 400 acre-feet treated.

Exposure Duration: 

HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months 

as intermediate-term. Exposure duration is determined by many things, including the exposed 

population, the use site, the pest pressure triggering the use of the pesticide, and the cultural 

practices surrounding that use site. For most agricultural uses, it is reasonable to believe that 

occupational handlers will not apply the same chemical every day for more than a one-month 

time frame; however, there may be a large agribusiness and/or commercial applicators who may 

apply a product over a period of weeks (e.g., completing multiple applications for multiple 

clients within a region). For fluridone, based on the proposed use, short- and intermediate-term

exposures are expected.

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were 

calculated for various levels of personal protective equipment (PPE). Results are presented for 

“baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, 

shoes plus socks, no protective gloves, and no respirator, as well as baseline with various levels 

of PPE as necessary (e.g., gloves, respirator, etc). The proposed product label for the preemergent cotton use directs applicators and other handlers to wear long sleeved shirt, long pants, 

chemical-resistant gloves, shoes plus socks and protective eyewear. The registered product 

labels do not require any PPE.

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A.

Combining Exposures/Risk Estimates:

Dermal and inhalation exposure estimates were combined in this assessment, since the 

toxicological effects for these exposure routes were the same. Dermal and inhalation exposure 

estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined dermal + inhalation dose (mg/kg/day)

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Proposed Cotton Use: There are no risk estimates of concern for the proposed cotton use (i.e., 

all MOEs ≥ LOC of 100; see Table 6.1.1). Occupational handler combined dermal and 

inhalation MOEs range from 230 to 640 with baseline clothing (long sleeved shirt, long pants, 

shoes plus socks, no gloves, and no respirator for all scenarios except aerial applicator where 

engineering controls were used). The proposed product label for the pre-emergent cotton use 

directs applicators and other handlers to wear long sleeved shirt, long pants, chemical-resistant 

gloves, shoes plus socks and protective eyewear. 

Registered Aquatic Uses: There are risk estimates of concern for some of the registered aquatic 

use scenarios (see Table 6.1.2). Occupational handler combined dermal and inhalation MOEs 
Page 19 of 37

range from 6.1 to 18,000 with baseline clothing (single layer clothing, shoes plus socks, no 

gloves, and no respirator for all scenarios except aerial applicator where engineering controls 

were used). The registered product labels for aquatic uses do not require any PPE. The scenario

of mixing/loading/applying product with handwand sprayer to aquatic sites was not of concern 

with the addition of gloves. The scenario of mixing/loading/applying product with backpack 

sprayer to aquatic sites was not of concern with the addition of double layer clothing and gloves.

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-sleeve 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.
Page 20 of 37

Table 6.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Proposed Uses of Fluridone on Cotton. 

Exposure Scenario Crop or 

Target

Level of 

Concern

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Combined

Mitigation 

Level

Mitigation 

Level

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE

(LOC = 100)8

Mixer/Loader

Mixing/loading liquid for 

Groundboom Application Cotton 100

SL/No G:

220

No R:

0.219

0.3 lb 

ai/acre 200 acres 0.0644 230 0.000164 91,000 230

Applicator

Applying Spray with 

Groundboom Application Cotton 100

SL/No G:

78.6

No R:

0.34

0.3 lb ai/acre 200 acres 0.023 650 0.000255 59,000 640

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: SL/ No G = Single layer, no gloves. 

2 Based on proposed label.

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ BW (kg).

5 Dermal MOE = Dermal NOAEL (15 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (kg).

7 Inhalation MOE = Inhalation NOAEL (15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (15 mg/kg/day) ÷ Dermal Dose + Inhalation Dose 

Table 6.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Aquatic Uses of Fluridone. 

Exposure Scenario Crop or 

Target

Level of 

Concern

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Combined

Mitigation 

Level

Mitigation 

Level

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE

(LOC = 100)8

Mixer/Loader

Mix/Load Liquid for 

Aerial/Boom Application 

or Direct Metering

Aquatic: 

Pond/Lake 100

SL/No G:

220

No R:

0.219

0.4 lb 

ai/acre-foot

30 acres / 7 

foot depth

0.0902 170 0.00023 65,000 170

Mix/Load Granular for 

Aerial/ Boom Application 

SL/No G:

8.4

No R:

1.7

0.00344 4,400 0.00179 8,400 2,900

Mix/load WDG for Aerial/ 

Boom application SL/ No G: 227 No R: 8.96 0.0931 160 0.00941 1,600 150
Page 21 of 37

Table 6.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Aquatic Uses of Fluridone. 

Exposure Scenario Crop or 

Target

Level of 

Concern

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Combined

Mitigation 

Level

Mitigation 

Level

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE

(LOC = 100)8

Mixing/loading liquid for 

direct metering 

Aquatic: 

Moving 

Water

100

SL/No G:

220

No R:

0.219

40 ppb; 0.11 

lb ai/acrefoot

200 CFS = 

400 acrefeet/day0.0472 320 0.000121 120,000 320

Applicator

Applying spray with Aerial 

Application

Aquatic: 

Pond/Lake 100

Eng. Control: 

2.08

Eng. Control: 

0.0049

0.4 lb 

ai/acre-foot

30 acres / 

7 foot 

depth

0.000853 18,000 0.0000052 2,900,000 18,000

Applying spray with Boat 

Boom Application

SL/No G:

78.6

No R:

0.34

0.032 470 0.000358 42,000 460

Applying granular with 

Aerial Application

Eng. Control:

1.7

Eng. Control:

1.3

0.000697 22,000 0.00136 11,000 7,300

Applying granular with 

boat spreader

SL/No G:

9.9

No R:

1.2

0.00406 3,700 0.00126 12,000 2,800

Mixer/loader/Applicator

Mixing/loading/applying 

liquid/WDG with backpack 

sprayer

Aquatic: 

Pond/Lake 100

SL/No G:

8260

No R:

2.58

0.4 lb 

ai/acre-foot 5 acre / 1 

foot depth

0.0804 190 0.0000645 230,000 190

Mixing/loading/applying 

liquid/WDG with 

handwand sprayer

SL/No G: 

100,000 No R:

30

0.975 15

0.00075 20,000

15

SL/G: 430 0.00419 3,600 3,100

Mixing/loading/applying 

liquid/WDG with handgun 

sprayer

SL/No G:

1300

No R: 

3.9

0.0127 1,200 0.0000975 150,000 1,200

Loading/applying granules 

with backpack SL/No G: 155 No R: 23.8 0.00151 9,900 0.000595 25,000 7,100

Mixing/loading/applying 

liquid/WDG with backpack 

sprayer Static Canal 100

SL/No G:

8260 No R:

2.58 2 lb ai/acre 2.5 acres

0.201 75

0.000161 93,000

75

SL/G: 8260 0.201 75 75

DL/G: 4120 0.1 150 150

Mixing/loading/applying SL/No G: No R: 2.44 6.1 0.00188 8,000 6.1
Page 22 of 37

Table 6.1.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Aquatic Uses of Fluridone. 

Exposure Scenario Crop or 

Target

Level of 

Concern

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Combined

Mitigation 

Level

Mitigation 

Level

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE

(LOC = 100)8

liquid/WDG with 

handwand sprayer

100,000 30

SL/G: 430 0.0105 1,400 1,200

Mixing/loading/applying 

liquid/WDG with handgun 

sprayer

SL/No G:

1300

No R: 

3.9

0.0317 470 0.000244 61,000 470

Loading/applying granules 

with backpack SL/No G: 155 No R: 23.8 0.00378 4,000 0.00149 10,000 2,900

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: SL/ No G = Single layer, no gloves. SL/G = Single layer, gloves. No R = 

no respirator. Eng. Control = Engineering controls. Unit exposure for groundboom application used as surrogate for boat boom sprayer/spreader.

2 Based on registered labels.

3 Exposure Science Advisory Council Policy #9.1 or as described in Section 6.1 above.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ BW (kg).

5 Dermal MOE = Dermal NOAEL (15 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (kg).

7 Inhalation MOE = Inhalation NOAEL (15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (15 mg/kg/day) ÷ Dermal Dose + Inhalation Dose 
Page 23 of 37

6.2 Occupational Post-application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

6.2.1 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.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-0037). The agency 

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

subsequent Volatilization Screening Analysis 

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

Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for fluridone.

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.

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Proposed Cotton Use: As the proposed use is on pre-plant or pre-emergent cotton, no 

occupational post-application dermal exposure to residues on foliage is expected.

Registered Aquatic Use: Since the currently registered uses of fluridone are in aquatic 

environments, there are no occupational post-application activities which would result in 

occupational exposures from treated bodies of water. While scouting may include identifying 

aquatic weed re-growth, this activity is not conducted until a few weeks after application. 

Therefore, occupational post-application exposure of workers to previously treated water bodies/ 

dry canals is expected to be negligible.

Restricted Entry Interval
Page 24 of 37

Proposed Cotton Use: The REI specified on the proposed label is based on the acute toxicity of 

fluridone. Fluridone is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) 

(2) (iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin 

irritation are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection 

Statement interim REI of 12 hours is adequate to protect agricultural workers from postapplication exposures to fluridone. The REI of 24 hours on the proposed label for the cotton use

is adequate and meets the minimum WPS requirements. It should be noted that the proposed 

label is a multiple active ingredient product, and should be considered when setting the REI for 

the end-use product.

Registered Aquatic Use: As application to aquatic areas do not fall under the purview of WPS 

and re-entry exposure is considered to be negligible, an REI is not applicable for these uses.
Page 25 of 37

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms

Residential Non-cancer Handler Algorithms

Handler exposure can result from treating aquatic sites in residential settings (e.g., backyard 

ponds or fountains) with pesticides. Some key assumptions for these assessments include:

 Adults are considered the index lifestage for this scenario as it is assumed that pesticides 

are applied by adults only (i.e., individuals 16 years and older).

 All application equipment and methods are assumed feasible unless prohibited by the 

product label.

Dermal and Inhalation Handler Exposure Algorithm

Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given 

formulation-application method combination, is estimated by multiplying the formulationapplication method-specific unit exposure by an estimate of the amount of active ingredient 

handled in a day, using the equation below:

E = UE ∗ AR ∗ A ∗ D

where:

E = exposure (mg/day);

UE = unit exposure (mg/lb ai);

AR =application rate (e.g., lb ai/ft2, lb ai/ft3, lb ai/A-ft); 

A = area treated (e.g., ft2/day, A/day); and

D = depth of water body treated (ft).

NOTE: The input for the depth of the water body treated is only applicable if the application 

rate is given per volume (i.e., lb ai/ft3or lb ai/A-ft).

Dermal and/or inhalation absorbed doses normalized to body weight are calculated as:

D =

E ∗ AF

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day);

AF = absorption factor (dermal and/or inhalation); and

BW = body weight (kg).

Handler exposure for applications to aquatic sites is generally considered short-term in duration. 

Refinement of this dose estimate to reflect a more accurate short-term multi-day exposure profile 
Page 26 of 37

can be accomplished by accounting for various factors such as the product-specific application 

regimen.

Dermal and Inhalation Handler Exposure Algorithm Inputs and Assumptions

Recommended values for handler exposure (inhalation and dermal) assessments are provided in 

the Draft 2015 Aquatic SOP. Following these tables, each scenario-specific input parameter is 

described in more detail. This description includes a summary of i) key assumptions, ii) data 

sources used to derive recommended input values, and iii) discussion of limitations that should 

be addressed when characterizing exposure.

Table A-1: Aquatic Sites – Recommended Residential Handler Exposure Factor Point Estimates.

Exposure Factor

(units) Point Estimate(s)

Application Rate (mass ai per unit area or volume) 0.12 lb ai/A-ft

Area treated Ornamental backyard pond 500 square feet

Recreational and fish pond 2.5 acres

Depth of water body (ft) Ornamental backyard pond 2

Recreational and fish pond 7

Body Weight (kg) 80

Amount of active ingredient Handled

The algorithm for estimating handler exposure requires some estimate of the amount of active 

ingredient handled per day. This factor varies based on the type of equipment or application 

method used and is estimated based on the application rate specified on the product label. First, 

the assessor should assemble application rate information in terms of active ingredient per area 

or volume treated (e.g., lb ai/acre, lb ai/1000 ft2, lb ai/A-ft, lb ai/ft3). Data on the amount of 

active ingredient handled are limited and difficult to collect. The amounts of active ingredient 

handled presented in this SOP are reasonable high-end assumptions for typical residential aquatic 

applications. 

For residential homeowner applications to backyard or recreational ponds, information on the 

amount of product used or the area treated is largely unavailable. Therefore, a general internet 

search was conducted9as well as review of the GENEEC model for aquatic ecological exposure 

assessment which has assumptions for “standard agricultural field-farm ponds”10. Depending on 

the use sites noted on the label, the following are recommendations for area treated for 

residential aquatic use sites:

 500 square feet surface area and a 2 foot depth for ornamental backyard ponds, and

 2.5 acres surface area and 7 feet depth for recreational and fish ponds.

It should be noted that the depth of the water body is only necessary in the exposure equation if 

the application rate is given per volume (i.e., lb ai/ft3or lb ai/A-ft). 

Residential Non-cancer Post-application Algorithms

 

9 Specific citations can be found in the References section at the end of the draft Aquatic SOP (November 2015).

10 http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/geneec2-description
Page 27 of 37

Post-application exposure can result from conducting activities in previously treated areas, such 

as swimming in lakes and ponds following pesticide applications by professional pesticide 

applicators or by homeowners themselves. It is assumed that post-application exposure will 

occur as a result of swimming in larger aquatic areas that may be treated by commercial 

applicators and/or homeowners, such as lakes and recreational ponds. It is not anticipated that 

post-application exposure would occur after homeowner applications to smaller aquatic areas 

such as ornamental backyard ponds or fountains. Adults and children 3 < 6 years old are 

considered the index lifestages for this exposure scenario as it is assumed that younger children 

(i.e., < 3 years old) won’t spend as much time swimming in lakes/ponds. Older children (6 to 

<11 years old and 11 to <16 years old) may spend slightly more time swimming on average, but 

the differences in other inputs (e.g., body weight, body surface area, inhalation rates) offset the 

higher exposure time input. The exposures estimated for children 3 to <6 years old are 

anticipated to be protective of older children engaging in similar activities. 

The equations and inputs for estimating exposures from recreational swimming in treated aquatic 

areas are generally derived from the SWIMODEL, developed by EPA as a screening tool to 

conduct exposure assessments of pesticides found in swimming pools and spas, and EPA’s Risk 

Assessment Guidance for Superfund – Part E, Supplemental Guidance for Dermal Risk 

Assessment (“RAGS-E”). However, some of the inputs and parameters have been updated to 

reflect use in bodies of water (e.g., lakes, ponds) as opposed to swimming pools. 

It should be noted that there may be additional routes of exposure from swimming in treated 

waters, such as buccal/sublingual (absorbed through the mouth), orbital/nasal (absorbed through 

the eyes or nose), and aural (absorbed through the ear). It is generally assumed that exposure 

through these routes will be less than exposure via the dermal, inhalation and oral routes. 

Therefore, these additional routes are not recommended to be routinely assessed for recreational 

swimmers.

Post-application Inhalation Exposure Assessment

Post-application inhalation exposure during recreational swimming is dependent on three factors: 

the volatility of the chemical, inhalation rate, and exposure time. Considering the strengths and 

limitations of available data and behavioral characteristics of potentially exposed lifestages, postapplication inhalation exposure is assessed for adults and children 3 < 6 years old. 

Post-application Inhalation Exposure Algorithm

The algorithm to calculate daily exposure and dose is shown below. Residential post-application 

exposure assessment must include calculation of exposure on the day of application. Therefore, 

though an assessment can present exposures for any day “t” following the application, it must 

include “day 0” exposure.

E= Vp* IR * ET

where:
Page 28 of 37

E = exposure (mg/day);

Vp = chemical-specific vapor concentration (mg/m3),

IR = inhalation rate (m3/hr), and

ET = exposure time (hrs/day).

Vp= Cw* H

,

*1,000 

L

m3

where:

Vp = chemical-specific vapor concentration (mg/m3),

Cw = chemical concentration in water (mg/L), and

H’ = dimensionless Henry’s Law constant (unitless).

H

'= 

HLC

R*T

where:

H’ = dimensionless Henry’s Law constant (unitless),

HLC = Henry’s law constant (atm-m3/mole),

R = gas constant (8.19E-5 atm-m3/mole-K), and 

T = ambient temperature in terms of Kelvin units (293K = 20oC).

Absorbed inhalation dose, normalized to body weight, is calculated as:

D= 

E*AF

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day);

AF = absorption factor (inhalation); and

BW = body weight (kg).

Post-application inhalation exposure following recreational swimming in treated aquatic areas is 

generally considered short-term in duration. Refinement of this dose estimate to reflect a more 

accurate short-term multi-day exposure profile can be accomplished by accounting for various 

factors, such as residue dissipation, product-specific re-treatment intervals, and activity patterns. 

If longer-term assessments (i.e., intermediate-, long-term, or lifetime exposures) are deemed 

necessary, similar refinements to more accurately reflect the exposure profile are recommended.

Post-application Inhalation Exposure Algorithm Inputs and Assumptions

Recommended values for post-application inhalation exposure assessments are provided in the 

table below. Following this table, each scenario-specific input parameter is described in more 

detail. This description includes a summary of i) key assumptions; ii) data sources used to derive 
Page 29 of 37

recommended input values; and iii) discussion of limitations that should be addressed when 

characterizing exposure. 

Table A-3: Aquatic Applications – Recommended Point Estimates for Post-Application Inhalation 

Exposure Factors.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Vp Chemical-specific vapor concentration (mg/m3)

Calculated based on chemical concentration 

in water and dimensionless Henry’s law 

constant

Cw Chemical concentration in water (mg/L) 0.15 for fluridone; 0.027 mg/L for NMF

H’ Dimensionless Henry’s Law constant (unitless) 3.38E-07 for fluridone; 8.21E-07 for NMF

HLC Henry’s Law constant (atm-m3/mole) 8.10E-09 for fluridone; 1.97E-08 for NMF

R Gas constant (atm-m3/mole-K) 8.19E-5 

T Ambient temperature in terms of Kelvin units (K) 293

IR Inhalation rate (m3/hr)

Adult 0.64

Children 3 to <6 years 

old 0.42

ET Exposure Time (hrs 

per day)

Adult 0.1

Children 3 to <6 years 

old 0.25

BW Body weight (kg) Adults 80

Children 3 < 6 years old 19

Post-application Dermal Exposure Assessment

Post-application dermal exposure resulting from recreational swimming in previously treated 

aquatic areas are based on the chemical properties of the active ingredient and exposure factors 

such as surface area and exposure time. Considering the strengths and limitations of available 

data and behavioral characteristics of potentially exposed lifestages, post-application dermal 

exposure is assessed for adults and children 3 < 6 years old. 

Post-application Dermal Exposure Algorithm

The algorithm to calculate daily exposure and dose is shown below. Residential post-application 

exposure assessment must include calculation of exposure on the day of application. Therefore, 

though an assessment can present exposures for any day “t” following the application, it must 

include “day 0” exposure.

E = Cw ∗ Kp ∗ SA ∗ ET ∗ CF

Where:

E = exposure (mg/day),

Cw = chemical concentration in water (mg/L),

Kp = permeability constant (see equation below),

SA = surface area (cm2),

ET = exposure time (hrs/day),
Page 30 of 37

CF = conversion factor (0.001 L/cm3)

Kp = 10[−2.72+ (0.71∗log Kow)− (0.0061∗MW)]

Where:

Kp = permeability constant (cm/hr),

Kow = octanol water coefficient,

MW = molecular weight (g/mol).

Absorbed dermal dose, normalized to body weight, is calculated as:

D =

E

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day); and

BW = body weight (kg).

Post-application dermal exposure following applications to aquatic areas is generally considered 

short-term in duration. Refinement of this dose estimate to reflect a more accurate short-term 

multi-day exposure profile can be accomplished by accounting for various factors such as 

residue dissipation, product-specific re-treatment intervals, and activity patterns. If longer-term 

assessments (i.e., intermediate-, long-term, or lifetime exposures) are deemed necessary, similar 

refinements to more accurately reflect the exposure profile are recommended.

Post-application Dermal Exposure Algorithm Inputs and Assumptions

Recommended values for post-application dermal exposure assessments are provided in Table 

below. Following this table, each scenario-specific input parameter is described in more detail. 

This description includes a summary of i) key assumptions; ii) data sources used to derive 

recommended input values; and iii) discussion of limitations that should be addressed when 

characterizing exposure. 

Table A-4: Aquatic Applications – Recommended Point Estimates for Post-Application Dermal 

Exposure Factors.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Cw Chemical concentration in water (mg/L) 0.15 for fluridone; 

0.027 for NMF

Kp Permeability constant 0.0763 for fluridone; 

0.000359 for NMF

SA Surface area (cm2)

Adults 19,500

Children 3 < 6 years old 7,600

ET Exposure Time (hrs per day) Adults 0.1
Page 31 of 37

Table A-4: Aquatic Applications – Recommended Point Estimates for Post-Application Dermal 

Exposure Factors.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Children 3 < 6 years old 0.25

BW Body weight (kg) Adults 80 kg for fluridone and 69 kg 

for NMF

Children 3 < 6 years old 19

Post-application Non-Dietary Ingestion Exposure Assessment

This SOP provides a standard method for estimating the dose for adults and children 3 < 6 years 

old from incidental ingestion of water from treated aquatic areas (e.g., lakes). This scenario 

assumes that swimmers ingest water that enters their mouth during swimming or playing in the 

treated water. 

Post-application Incidental Ingestion Exposure Algorithm

Exposure from incidental ingestion of treated water is calculated as follows:

E = Cw ∗ IgR ∗ ET

Where:

E = exposure (mg/day),

Cw = chemical concentration in water (mg/L),

IgR = ingestion rate of water (L/hr),

ET = exposure time (hrs/day).

Dose, normalized to body weight, is calculated as:

D =

E

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day);

BW = body weight (kg).

Post-application incidental ingestion following aquatic applications is generally considered 

short-term in duration. Refinement of this dose estimate to reflect a more accurate short-term 

multi-day exposure profile can be accomplished by accounting for various factors such as 

residue dissipation, product-specific re-treatment intervals, and activity patterns. If longer-term 

assessments (i.e., intermediate-, long-term, or lifetime exposures) are deemed necessary, similar 

refinements to more accurately reflect the exposure profile are recommended. 

Post-application Incidental Ingestion Exposure Algorithm Inputs and Assumptions
Page 32 of 37

Recommended values for post-application incidental ingestion exposure assessments are 

provided in the table below. Following this table, each scenario-specific input parameter is 

described in more detail. This description includes a summary of i) key assumptions; ii) data 

sources used to derive recommended input values; and iii) discussion of limitations that should 

be addressed when characterizing exposure. 

Table A-5: Aquatic Applications – Recommended Point Estimates for Post-Application Incidental 

Ingestion Exposure Factors.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Cw Chemical concentration in water (mg/L) 0.15 for fluridone; 

0.027 mg/L for NMF

IgR Ingestion rate (L/hr) 0.05

ET Exposure Time

(hours per day)

Adults 0.1

Children 3 < 6 years old 0.25

BW Body weight

(kg)

Adults 80 kg for fluridone and 69 kg 

for NMF

Children 3 < 6 years old 19
Page 33 of 37

Occupational Non-cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = area treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are 

calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to 

the daily dose of concern. The daily dermal and inhalation dose received by occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Page 34 of 37

Appendix B. NMF Exposure and Risk Assessment

N-methylformamide (NMF) is a major degradate of fluridone that may be formed in surface, as 

well as ground, water by the photolysis of fluridone. Fluridone is registered for use as an aquatic 

herbicide and is proposed for pre-emergent treatment of cotton. The use of fluridone as an 

aquatic pesticide may result in residential post-application exposure to NMF while swimming in 

treated water. 

The toxicology database for NMF is limited to one developmental study that was reported in the 

literature. This study indicated that NMF causes skeletal malformations in both rats and rabbits 

with a NOAEL of 10 mg/kg/day. Exposure to NMF can occur from swimming in water treated 

with fluridone as well as in drinking water. The POD of 10 mg/kg/day was used to assess all 

routes (dermal, inhalation, and incidental oral). The same three uncertainty factors were applied 

to each exposure scenario: 10x for interspecies extrapolation (UFA), 10x for intraspecies 

variation (UFH), and 10x to account for the lack of NMF toxicity studies (UFDB).

Table B.1. Summary of Toxicological Doses and Endpoints for NMF for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure

Scenario

Point of 

Departure

Uncertainty 

Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-

49 years)

NOAEL = 

10 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=10x

aRfD = 0.01 

mg/kg/day

Developmental Toxicity in Rats and Rabbits 

LOAEL = 75 mg/kg/day for rats and 50 

mg/kg/day for rabbits based on decreased fetal 

viability and weight; increased incidence of 

skeletal malformations

Acute Dietary 

(General

population 

including 

infants and 

children)

The acute effects observed in the developmental toxicity study in rats and rabbits were not 

applicable to the general population.

Chronic 

Dietary

NOAEL= 

10 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=10x

cRfD = 0.01 

mg/kg/day

Developmental Toxicity in Rats and Rabbits 

LOAEL = 75 mg/kg/day for rats and 50 

mg/kg/day for rabbits based on body weight 

loss during gestation 

Incidental Oral

Short-Term

NOAEL= 

10 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=10x

MOE = 1000 Developmental Toxicity in Rats and Rabbits 

(same as chronic dietary) 
Page 35 of 37

Dermal

Short-Term

NOAEL= 

10 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=10x

MOE = 1000 Developmental Toxicity in Rats and Rabbits 

(same as chronic dietary)

Inhalation

Short-Term

NOAEL= 

10 

mg/kg/day

UFA=10x

UFH=10x

FQPA SF=10x

MOE = 1000 Developmental Toxicity in Rats and Rabbits 

(same as chronic dietary)

Cancer (oral, 

dermal, and 

inhalation)

No evidence of mutagenicity or carcinogenicity was observed in the single study available.

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

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). SF = safety factor. 

Since NMF may be formed in water via photolysis, residential exposures to NMF are anticipated 

for the aquatic uses of fluridone in order to be protective of possible exposures. No NMF 

exposure is anticipated from the proposed agricultural uses of fluridone. Post-application 

exposure to NMF in aquatic environments (i.e., adult and child swimmers) has been assessed 

according to HED’s November 2015 Draft Aquatic Use SOP. The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios: 

 Adults and children (3 to <6 years old) swimming in treated water (dermal, inhalation

and incidental ingestion)

Residential Post-Application Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. Each assumption and factor is detailed in the Draft 2015 

Aquatic Use SOP.

Application Rate: Concentrations of NMF were estimated assuming NMF conversion efficiency 

of 100%, and by adjusting for the ratio of the fluridone molecular weight of 329 g/mol to the 

NMF molecular weight of 59 g/mol. A maximum concentration of 150 ppb (0.15 mg/L) was 

assumed for the fluridone assessment, therefore, a concentration of 27 ppb (0.027 mg/L) was 

used to assess aquatic exposure to the degradate, NMF.

Exposure Duration: Residential exposure is expected to be short-term in duration. 

Residential Post-Application Cancer and Non-Cancer Exposure and Risk Equations

The algorithms used to estimate residential non-cancer post-application exposure and dose can 

be found in the Draft November 2015 Aquatic Use SOP.
Page 36 of 37

Combining Non-Cancer Exposure and Risk Estimates

Since dermal, inhalation and incidental oral exposure routes share a common toxicological 

endpoint, exposure estimates have been combined for those routes. 

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

For NMF, the combined MOE for adult swimmers is 4,400,000 and for child swimmers is 

530,000; therefore, there are no risk estimates of concern (LOC = 1000). 

Table E.4. Residential Post-application Non-cancer Exposure and Risk Estimates for NMF.

Lifestage

Post-application Exposure 

Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3

Combined Routes

(X indicates 

included in 

Combined MOE)

Combined MOEs

(LOC = 1000) Use Site Route of 

Exposure

Adult

Aquatic

Dermal

27 ppb

(0.027 mg/L)

2.7E-7 36,000,000 X

4,400,000 Inhalation 2.06E-8 490,000,000 X

Incidental 

Ingestion 1.96E-6 5,100,000 X

Child (3 to 

<6 years 

old)

Dermal 9.7E-7 10,000,000 X

530,000 Inhalation 1.22E-7 82,000,000 X

Incidental 

Ingestion 1.78E-5 560,000 X

1 Based on application of fluridone and conversion to NMF.

2 Dose (mg/kg/day) equations:

 Inhalation Dose (mg/kg/day) = [Concentration in water (0.027 mg/L) * Dimensionless Henry’s law constant (8.21E-07) * CF (1000 

L/m3) * IR (0.64 m3/hr for adults and 0.32 m3/hr for children) * Exposure time (0.1 hr for adults and 0.25 hr for children)] / BW (69 kg 

for adults and 19 kg for children).

 Dermal dose (mg/kg/day) = [Concentration in water (0.027 mg/L) * Permeability constant (0.00039) * Surface area (19,500 cm2for 

adults and 7,600 cm2for children) * Exposure time (0.1 hr for adults and 0.25 hr for children)] / BW (69 kg for adults and 19 kg for 

children).

 Incidental ingestion dose (mg/kg/day) = [Concentration in water (0.027 mg/L) * Ingestion rate (0.05 L/hr) * Exposure time (0.1 hr for 

adults and 0.25 hr for children)] / BW (69 kg for adults and 19 kg for children).

3 MOE = POD (10 mg/kg/day) ÷ Dose (mg/kg/day).

4 Combined MOE = 1 ÷ (1/dermal MOE) + (1/inhalation MOE) + (1/incidental oral MOE), where applicable.

Table E.5 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for NMF.

 The recommended residential exposure for use in the adult aggregate assessment reflects 

dermal and incidental oral exposures from post-application exposure to aquatic 

applications.

 The recommended residential exposure for use in the child (3 to <6 years old) aggregate 

assessment reflects dermal and incidental oral exposures from post-application exposure 

to aquatic applications.

Table E.5. Recommendations for the Residential Exposures for the NMF Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE (LOC = 1000)2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Adult Swimming 2.7E-7 2.06E-8 1.96E-6 2.3E-6 36,000,000 490,000,000 5,100,000 4,400,000

Child (3 to 

<6 years old) Swimming 9.7E-7 1.22E-7 1.78E-5 1.9E-5 10,000,000 82,000,000 560,000 530,000
Page 37 of 37

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + incidental oral 

(where applicable).

2 MOE = the MOEs associated with the highest residential doses. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental 

Oral MOE), where applicable.

Occupational exposure to NMF is not anticipated since NMF only forms in water due to the 

photolysis of fluridone. In addition, the proposed use on cotton is for pre-plant or pre-emergent 

use; therefore, occupational post-application dermal exposures to residues on foliage are not 

expected. For the aquatic uses of fluridone, occupational post-application exposure of workers 

to previously treated water bodies is expected to be negligible, since post-application activities 

are not anticipated for occupational workers post-treatment.