Dat e:

S ubj ec t: UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D

. C

. 20460



### January 6, 2016 OFF ICE OF CHEM IC AL SAFE T Y AND POLLUTION PREVENTION



### F luridonc. Occupational and Re s idential Exposure Assessment fo r Registration R ev i ew and to S upp o rt the R egistra tion of a Prop osed Use on Cotton.

P C Co de: I 1 2900
D ecis i on No. : 494948 P e titi o n No.: 4F8308 OP Bar codc: 0431020 R eg i s tration No.: 67690-NEW
R eg ul atory Act i on: Reg. Review / Section 3 Ri s k Assessme nt T y pe: Occupational / Re s idential Exposure Assess m e nt T XR No.: NA Case No.: 7200 CAS No.: 59756-60-4 40 C FR : 18 0.420 MRID No.: NA



### F rom:

T hrou g h:

To: ('\ 

### A l exa ndra Gavelek

, B i o l ogist

# \~**~** 

# l**~** Kelly M

. Lowe, E n viro nment a l Sc i e nti st**j~ ~**  

### Ri sk Assessment Branch YN JJ 

## 0
H ea l th Effects Di vision (7509P)

M ich

. ael Metzge r , Branch C hi ef/ 

# j J () / f 

# j\ ______---- Ri sk Assessment Branch YN II

# ~v1\td~ - 

# fl 

# er

H

ealt h Effects Di vis i on (7509 P )

and

B a rr y O'Keefe, Bio l og i st

## ~**~** , Bridgett Bobowiec, Biolog i st

### ~**~** Exposure Science Advisory Committee (ExpoSAC) I 

### H E D

SaraJ1 Meadows, R i sk Manage r R ev i ewe r Ka thr yn Mo nt ague, Risk Manager R

eg istration Division

And

L e i g h Rimm er, Chemical Rev i ew Manager Tom Myers, Team Leader Ke vin Costello, B ranch Chief P

est i cide Re

- Eva l uation Division

Pa ge I of 3 7Int ro du c ti o n

Th e P estic id e Re- eva lu a tion Divisi o n ( PRO ) r eq u ested that the Health Effects Division (HE D ) conduct an occupational expos ur e / ri sk assessment for the registered uses of fluridone as part of Registration Review. This memorandum co n tains HED 's occupational / residential exposure and risk assessment required during R eg i strat i on Review to r eflec t th e u pdated sc i e nc e polici es and procedures.

In ad diti o n , th e Registration Di v i s i o n ( RD ) requested that HED conduct an exposure and risk

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

, this exposure assessme nt also in corporates the proposed new use on cotton.



### It i s HED policy to u se the best**~vailable** data to assess exposure

. Several sources of gene ri c d ata were u se d in this assessment as surrogate data in the absence of chemica l- spec ifi c data

, includin g P est ici de H and l ers Exposure D atabase Version 1

. 1 ( PH E D 1.1 ); th e Ag ricultural Handler Exposure T ask Force (AHE T F) database; and th e Agricultural R ee ntr y Task Fo r ce (A RTF ) database. Some of th ese data a re proprietary

, and s ubj ec t to th e data protection
p rov i s ion s of the Federal l n sec ticid e, Fungicide, a nd Rodenticide Act (FIFRA).

No t e: This memorandum was r ev i ewed by the Exposure Science Advisory Committee (ExpoSAC) on Jun e 4

, 2015.

Pa g e 2 of37Page 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 Estimate s

................................ .............. 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

..................... 25Page 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 irrigatio n canals, including dry or dewatered areas of these sites; in dr y 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 a re formulated as liquids, granulars, and water dispersible granulars (WDGs). In a quatic settings, f luridone 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 meteri ng 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 liqui d 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, sho es 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 a quatic 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

- e mergent, and (2) occupational post

- application activities are not anticipated after the use of fluridone in aquatic environments. Residential handler (adults) and post

application exposures (a dults 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 (MO E) 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”.

A nother 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 rema ins 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

- applicat i on exposure assessment assessed adults and children (3 to <6 years old) who may be exposed fluri done 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 fro m 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 n o 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 wer e no risks of concer n (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 ri sk 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 MO Es

. 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 r esidues 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

- applicat ion activities which would result in occupational exposures from treated bodies of water. As application s 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 dat a 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 ethicsPage 6 of 37



### review may have included review by the Human Studies Review Board. Descriptions of d ata sources, as well as guidance on their use, can be found at the Agency website 1



### .

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 a nd 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 fo r 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 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.

Registered Aquatic Uses:

 There are no risk esti mates 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 fl uridone, 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 b aseline 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 doubl e 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 a quatic 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.htmlPage 7 of 37



### applicable for these uses.

2.2 Label Recommendations

Proposed Cotton Use: No label recommendations.

Registered Aquatic Use : Although aquatic appli cations do not fall under the pu rview 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 fo r 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 or al, 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 t he subchronic inhalation toxicity study ha s 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 intraspecie s 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”.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 Intermediate

Term NOAEL = 15

mg/kg/day

39% DAF UF A = 10x

UF H =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 Short

and Intermediate Term NOAEL = 15

mg/kg/day UF A = 10x

UF H =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 Intermediate

Term exposures NOAEL = 15

mg/kg/day UF A = 10x

UF H =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 en vironmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 th e 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, th e 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 ap plied: (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 handheldPage 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 in clude 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/acre

foot 150 ppb: 8.1 lb /acre

- foot = 0.4 lb ai/acre

foot 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/acre

foot 150 ppb: 15 lb / acre

- foot = 0.4 lb ai/acre

foot

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/acr e

- 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 usesPage 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 healt h 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 t he 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 ass umed to complete all elements of an application without use of any protective equipment.

The ready

- to

- use (R TU ) aquatic product s 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 application s

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/ft 3



### .
Unit Exposures and Area Treated or Amount Handled : Unit exposure values to represent a homeowner pou ring a RTU formulation have been adjusted from the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 2 

### ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, ca n be found at the Agency website 3



### . 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. Es timates for area treated or amount handl ed 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 SOPs 4 

### and/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.htmlPage 11 of 37



### Combining Exposures/Risk Estimate s: Dermal and inhalation risk estimate s were combined in this assessment, since the toxicological effects for these exposure routes were the same . Dermal and inhalation risk estimate s were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined D ermal + I nhalation 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 1,4 00 ,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 Rate 2 Area Treated or

Amount Handled Daily 3 Dermal Inhalation Combined

Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 MOE (LOC = 100) 8 Mixer/Loader/Applicator Ready

- to

- use

– Open Pour to Recreational Ponds 100 0.232 0.219 0.12 lb ai/acre

foot 2.5 acres, 7 foot

depth 0.00 24 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 ft 2 , 2 foot

depth 0.00000 31 4,800 ,000 0.0000075 2,000,000 1,4 00,000

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) ÷ In halation 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 individual s 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 quantitati ve 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

Rate 1 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 1,6 00,000 X

Child (3 to <6 years old) Dermal 0.00114 13 ,000 X

12 ,000 Inhalation 2.8 E

- 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 derm al and inhalation exposure f rom 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 post

application exposure to aquatic applications.

Table 5. 3 .1. Recommendations for the Resident ial Exposures for the Fluridone Aggregate Assessment.

Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Adult Handler

–

RTU 0 .00 24 0.0057 N/A 0.0 0 81 6,300 2,600 N/A 1,800

Child (3 to < 6 years old) Swimming 0.00114 2.8E

- 7 9.9E

- 5 0.00 12 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 Estimat es 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 off

target 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 b ased 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 inhalatio n 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 consi dered 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
vary ing 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 r emainder 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 w as 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 becau se 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 proc ess 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 sp ecific 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 it s herbicidal mode of action require s 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 cove r the surface area of the weeds. Foir the aquatic use applications, i t 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 . T he 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 quantitat ive 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 appli cation 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:

6 http://www.a gdrift.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 90 th 

### percentile results.

The applicable LO C 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 conc ern 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/cm 2 ) 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)

– Combine d 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/cm 2 ; where F = 0.1 and D = 0.10 per day



### 5

. 5 Non

- occupational B ystander 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 200 9, 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 Sc reening 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 a nalysis 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 t ask. 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 develo ped 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 l iquid 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

 Mixi ng/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. Eac h 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 dat a 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 Tab le 7 

### ”, 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 website 8



### .
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 (endothal l 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 acre s of surf ace area and a depth of 1 foo t

. For st atic 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 c ubic 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 c hemical 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., glo ves, respirator, etc). The proposed product label for the pre

emergent cotton use direct s applicators and other handlers to wear long sleeved shirt, long pants, chemical

- resistant gloves, shoes plus socks and protective eyewear

. The registered product la bels 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 inhala tion 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 us es 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 n ot 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 Ex posure 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 Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 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 ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × 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 ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/ac re 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 Ex posure 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 Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 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 150Page 21 of 37

Table 6.1. 2 . Occupational Handler Non

- Cancer Ex posure 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 Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 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/acre

foot 200 CFS =

400 acre

feet/day 0.0472 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 2 3 0 ,000 190

Mixing/loading/applying liquid /WDG with handwand sprayer SL/No G: 100,000 No R:

30 0.975 15 0.00075 20,0 00 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 6.1Page 22 of 37

Table 6.1. 2 . Occupational Handler Non

- Cancer Ex posure 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 Rate 2 Area

Treated or Amount Handled Daily 3 Dermal Inhalation Combined

Mitigation Level Mitigation

Level Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 6 MOE 7 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 regist ered labels

. 3 Exposure Science Advisory Council Policy #9.1 or as described in Section 6.1 above. 4 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × 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 ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/ac re 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 DosePage 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 re

entry 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 o n 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 perf orming 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 relate d 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 toxicol ogical studies) or f urther 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 , ther e 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 cana ls is expected to be negligible.

Restricted Entry IntervalPage 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 Cate gory 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 irri t ation are assigned a 12

- hour REI. Therefore, the [156 subpa rt K] Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural workers from post

application exposures to fluridone

. The REI of 24 hours on the proposed label for the cotton use is adequate and meets the minimum WPS requirem ents. 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 aquat ic areas do not fall under the pu rview 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 D aily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given formulation

- application method combination, is estimated by multiplying the formulation

application method

- specific unit exposure by an estimate of the amount of active ingredient handled in a day, u sing 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/ft 2 

### , lb ai/ft 3 

### , lb ai/A

- ft); A = area treated (e.g., ft 2 

### /day, A/day); and D = depth of water body treated (ft).

N OTE: 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/ft 3 

### or 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 profilePage 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 Estimat es. 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 o n 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 ft 2 

### , lb ai/A

- ft, lb ai/ft 3 

### ). 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 conducted 9 

### as 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 ac res 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/ft 3 

### or 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/g eneec2

- descriptionPage 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

- a pplication 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 estimatin g 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 t hat 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 e xposure 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 characterist ics of potentially exposed lifestages, post

application 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. R esidenti al 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= V p 

### * IR * ET

where :Page 28 of 37



### E = exposure (mg/day); V p 

### = chemical

- specific vapor concentration (mg/m 3 

### ), IR = inhalation rate (m 3 

### /hr), and ET = exposure time (hrs/day).

V p 

### = C w 

### * H , 

### *1,000 L

m 3



### where: V p 

### = chemical

- specific vapor concentration (mg/m 3 

### ), C w 

### = 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

- m 3 

### /mole), R = gas constant (8.19E

- 5 atm

- m 3 

### /mole

- K), and T = a mbient temperature in terms of Kelvin units (293K = 20 o 

### C).

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 a ccomplished 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 re finements 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. Foll owing 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 derivePage 29 of 37



### recommended input values; and iii) discussion of limitations that should be ad dressed 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)

V p Chemical

- specific vapor concentration (mg/m 3 ) Calculated based on chemical concentration in water and dimensionless Henry’s law

constant C w Chemical concentration in water (mg/L) 0.15 for fluridone; 0.027 mg/L for NMF
H’ Dimensionless Henry’s Law constant (unitless) 3.38 E

- 0 7 for fluridone; 8.21E

- 07 for NMF
HLC Henry’s Law constant ( atm

- m 3 /mole ) 8.10E

- 09 for fluridone; 1.97E

- 08 for NMF R Gas constant ( atm

- m 3 /mole

- K) 8.19E

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

IR Inhalation rate (m 3 /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 calcula te daily exposure and dose is shown below. R esidential 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, i t must include “day 0” exposure.

E = C w 

### ∗ K p 

### ∗ SA ∗ ET ∗ CF

Where: E = exposure (mg/day), C w 

### = chemical concentration in water (mg/L), K p 

### = permeability constant (see equation below), SA = surface area (cm 2 

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



### CF = conversion factor (0.001 L/cm 3 

### )

K p 

### = 10 [

− 2

. 72 + ( 0

. 71 ∗ log K ow )

− ( 0

. 0061 ∗ MW ) ]



### Where: K p 

### = permeability constant (cm/hr), K ow 

### = octanol water coefficient, MW = molecular weight (g/mol).

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

D = E
BW

w here : 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 refl ect 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

- , l ong

- 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)

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

K p Permeability constant 0.0763 for fluridone; 0.000359 for NMF

SA Surface area (cm 2 ) Adults 19,500 Children 3 < 6 years old 7,600 ET Exposure Time (hrs per day) Adults 0.1Page 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 = C w 

### ∗ IgR ∗ ET

Where: E = exposure (mg/day), C w 

### = chemical concentration in water (mg/L), IgR = ingestion rate of water (L/hr), ET = exposure time (hr s/day).

Dose, normalized to body weight, is calculated as:

D = E
BW

w here : 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 var ious 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 reflec t the exposure profile are recommended.

Post

- application Incidental Ingestion Exposure Algorithm Inputs and AssumptionsPage 32 of 37



### Recommended values for post

- application incidental ingestion exposure assessments are provided in the table below. Following this tab le, 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 c haracterizing exposure.

Table A

- 5 : Aquatic Applications

– Recommended Point Estimates for Post

- Application Incidental Ingestion Exposure Factors. Algorithm Notation Exposure Factor (units) Point Estimate(s)

C w 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 19Page 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 = e xposure (mg ai/day), UE = u nit e xposure (μ g ai/ lb ai), AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal ), and A = a rea 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 a bsorbed in a given scenario (mg ai/ kg / day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/or inhalation), and BW = body weight (kg)

.
Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated usin g 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 a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values a re calculated using the following formula:

MOE= POD
ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless), POD = p oint of d eparture (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

- methyl f ormamide (NMF) is a major degradate of fluridone that may be formed in surface, as well as gr ound, 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 N MF 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 app lied to each exposure scenario: 10x for interspecies extrapolation (UF A 

### ), 10x for intraspecies variation (UF H 

### ), and 10x to account for the lack of NMF toxicity studies (UF DB 

### ).

Table B.1. Summary of Toxicological Doses and Endpoints for NMF for Use in Diet ary and Non

Occupational 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 UF A =10x

UF H =10x FQPA SF=1 0x a RfD = 0.01

mg/kg/day Developmental Toxicit y 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 o f 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 UF A =10x

UF H =10x FQPA SF=1 0x c RfD = 0.01

mg/kg/day Developmental Toxicity in Rats and Rabbits

LOAEL = 75 mg/kg/day for ra ts and 50 mg/kg/day for rabbits based on body weight loss during gestation

Incidental Oral
Short

- Term NOAEL=

10 mg/kg/day UF A =10x

UF H =10x FQPA SF=1 0x MOE = 1000 Developmental Toxicity in Rats and Rabbits (same as chronic dietary)Page 35 of 37

Dermal
Short

- Term NOAEL=

10 mg/kg/day UF A =10x

UF H =10x FQPA SF=1 0x MOE = 1000 Developmental Toxicity in Rats and Rabbits (same as chronic dietary)

Inhalation
Short

- Term NOAEL=

10 mg/kg/day UF A =10x

UF H =10x FQPA SF=1 0x 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 ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 agric ultural 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: C oncentrations of NMF were estimated assumin g 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 expo sure 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 4,400,00 0 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

Rate 1 Dose

(mg/kg/day) 2 MOEs 3 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 ( 8.21 E

- 07 ) * CF (1000 L/m 3 ) * IR (0.64 m 3 /hr for adults and 0.32 m 3 /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 ( 0.0 0039 ) * Surface area (19,500 cm 2 for adults and 7,600 cm 2 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).

 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 re sidential exposure for use in the child (3 to <6 years old) aggreg ate 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 1.96 E

- 6 2.3E

- 6 36,000,000 490,000,000 5,100,000 4, 4 00,000

Child (3 to

< 6 years old) Swimming 9.7E

- 7 1.22E

- 7 1. 7 8E

- 5 1.9E

- 5 10,000,000 82,000,000 560,000 530,000Page 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 re sidues 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 occupationa l workers post

- treatment.