### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

DATE: February 23, 2010

MEMORANDUM

SUBJECT: Indaziflam: Occupational and Resi dential Exposure Assessment for Use of New Active Ingredient on Turf, Go lf Courses, Sod Farms, Christmas Tree Farms, Non-Crop Areas and Forestry.

PC Code: 080818 DP Number: D372538 MRID: 47443317; 47443316 Registration Nos.: 432-RUOO; 432-RUOL; 432-RUOA; 432-RUOT; 72155-IO; 72155-OR; 72155-ON Petition Nos: NA Regulatory Action: Section 3 Assessment Type: Single Chemical CAS Number: 730979-19-8 TXR No.: NA Decision No.: 398884 Case No. NA 40 CFR: NA



### FROM: Margarita Collantes, Biologist Risk Assessment Branch (RAB) II Health Effects Division (7509P)

THROUGH: Richard Loranger, Branch Senior Scientist Risk Assessment Branch (RAB) II Health Effects Division (7509P)

TO: Erik Kraft/James Tompkins, RM Team 25 Herbicide Branch Registration Division (7505P)

ACTION REQUESTED :

The Registration Division (RD) requested that Health Effects Divison (HED) conduct an exposure risk assessment for proposed uses of the new active ingredient indaziflam to control annual grasses and broadleaf weeds in residential and commercial lawns, golf course, sod farms, recreational turf, orname ntals, non-crop areas, Christmas tree farms and forested areas. Commercial and reside ntial handler and post application exposure assessments were conducted for the proposed Indaziflam uses.

Page 1 of 21

### TABLE OF CONTENTS

1.0 EXECUTIVE SUMMARY...................................................... ... 3

2.0. HAZARD CHARACTE RIZATION.......................................... ......5 2.1 Hazard Profile ............................................................ .....5 2.2 FQPA/Uncertainty Factors.......................................... .........6

3.0 PROPOSED USE PATTERNS........................ ............................7

4.0 RESIDENTIAL (NON-OCCUPATIONAL) RISK ................................9 4.1 Handler Exposure..............................................................9 4.2 Postapplication Exposure.....................................................11 4.2.1 Hand-To-Mouth .....................................................11 4.2.2 Object-To-Mouth ...................................................13 4.2.3 Incidental Ingestion of Soil ........................................14 4.2.5 Episodic Ingestion................................................... 15 4.3 Combined Residential Exposure and Risk............................... .16

5.0 OCCUPATIONAL RISK.............................................................17 5.1 Handler Exposure.............................................................17 5.2 Postapplication Exposure.....................................................21

Page 2 of 21

### 1.0 EXECUTIVE SUMMARY

Indaziflam ([1,3,5-triazine-2,4-diamine,N- [(1R2S)-2,3-dihydro-2,6-dimethyl-1H-inden1-yl]-6-(1-fluroethyl)]) is a new selective, pre-emergent and post- emergent alkylazine herbicide for control of many annual grasses and broadleaf weeds in lawns, golf course, sod farms, recreational turf, ornamentals, non-crop areas, Christmas tree farms and forested areas. It is also used as a pre-em ergent herbicide for weed control in parks, rail roads, utility, industria l and municipal sites, sidewalks and driveways. Indaziflam may be applied through a variety of application methods including: ground equipment, right of way handgun, backpack, broadcast and ro tary or drop type spreader, hand held equipment (low pressure, high pressure and trigger sprayer), and hose end sprayer.

There are currently no registered uses for indaziflam in the United States. This assessment will review six proposed products for use by commercial and professional applicators (formulated as a water soluble pack et and turf fertilizers) as well as three residential homeowners (formulated as a gr anule and liquid) produc ts. It should be noted that several of these products cont ain additional active ingredients. This assessment will only assess exposure resulti ng from the use of indaziflam. Proposed uses are anticipated to result in short- and intermediate-t erm durations of exposure.

Hazard Characterizatio n Indaziflam shows low acute toxicity by all rout es of exposure (Toxicity Category III, oral and dermal and Category IV, inhalation) and is not an ocular or dermal irritant or a dermal sensitizer.

An appropriate endpoint for short- or in termediate-term dermal exposure was not identified. No toxicity was observed in a 28-day dermal toxi city study in the rat up to the limit dose of 1000 mg/kg/day. Therefore, a short- and intermediate-term dermal exposure assessment was not conducted.

The short- and intermediate-term incident al oral and inhalatio n no observed adverse effect level (NOAEL) of 7.5 mg /kg/day was selected and based on brain, spinal cord and sciatic nerve degenerative lesi ons observed at the lowest obs erved adverse effect level (LOAEL) of 15 mg/kg/day from a s ubchronic oral dog (gavage) study.

Indaziflam is classified as “Not lik ely to be carcinogenic to humans.”

FQPA and Uncertainty Factors Although there are no food uses associ ated with the currently proposed uses, HED is reviewing a subsequent submission of proposed food uses. Therefore, the RABII team has considered the postnatal susceptibility of infants and children in determining appropriate uncertainty and safety fact ors for the non-food uses. HED recommends reduction of the FQPA safety factor to 1X, ba sed on (1) there is no ev idence of increased quantitative or qualitative pre- and/or postnatal susceptibil ity in a complete database that includes developmental reproductive a nd developmental neurotoxicity, and immunotoxicity studies; (2) developmental effect s in the rat that were observed, but only at high doses and in the presence of matern al/parental toxicity; and (3) selection of endpoints and doses for risk assessments that are protective of potential developmental

Page 3 of 21

### toxicity.

HED has retained the traditional uncertainty factors for inter-species extrapolation and 10X for intra-species variabilit y. Therefore, HED’s level of concern for residential and occupational handler and posta pplication exposure risk is equal to an MOE of 100. Scenarios resulting in MOEs greater than or equal to 100 are not of concern to HED.

Residential Handler Exposure : Three indaziflam turf products (i.e., Lawn 3 FL Concentrate/Ready-to-Spray, Lawn 3 FL Granule, and Lawn 3 FL Ready-To- Use) are proposed for use by home owners. These products are to be applied using hand held sprayers (pump style tank, hose end, and trigger) or drop/push rotary-type spreaders, and were assessed using the Pesticide Handlers Exposure Database (PHED) Surr ogate Exposure Guide and the Outdoor Residential Exposure Task Force (ORE FT) study (MRID 44972201) unit exposures to estimate handler exposure. Since a short-term dermal point was not selected, the only route of exposure addressed is via in halation. Handler i nhalation MOEs were significantly greater than 100 and are not of concern.

Residential Postapplication Exposure : Since residential postapplication scenarios occur outdoors where ther e is sufficient air exchange to reduce the potential for inhalati on exposure to minimal levels, a quantitative postapplication inhalation exposure assessment was not conducted. Furthermore, since a dermal endpoint was not selected the only pos tapplication residentia l scenario assessed for this action is oral non-dieta ry ingestion exposures for chil dren (i.e. soil ingestion, and hand-/object-to-mouth).

The children’s oral postapplic ation residential scenarios were assessed using the HED Draft Standard Operating Procedures (SOP ’s) for Residential Exposure Assessment, 2000. All short- and intermediate-term ha nd-to-mouth (HTM), object-to-mouth (OTM) and soil ingestion scenarios re sulted in MOEs greater than the level of concern (MOEs ≥ 100) and therefore pose no risk of concern to HED. Oral MOEs ranged from 5,300 to 2,100,000.

Occupational Handler Exposure : No chemical specific data were available to assess potential exposure to pesticide handlers. The estimates of exposure to pe sticide handlers are ba sed upon surrogate study data available in the PHED (v. 1.1, 1998) and from the Outdoor Residential Exposure Task Force (ORETF: MRID 44972201). Short- and intermediate-term inhalation risks for commercial lawn handlers are not of c oncern. Handler inhalation MOEs ranged from 2,900 to 6,000,000.

Occupational Postapplication Exposure HED assumes that inhalation exposures are mi nimal following outdoor applications of an active ingredient, due to the large volume of air exchange. Therefore, a separate inhalation postapplication risk assessment was not conducte d. Since a dermal endpoint was not selected, a dermal postapplicati on exposure assessment was not conducted. Therefore, the restricted entry interval (REI) will be based on the acute toxicity of the technical, indaziflam. Since indaziflam has low acute toxicity by a ll routes of exposure

Page 4 of 21

### and is not an ocular or dermal irritant or a dermal sensit izer, HED has no objection to the proposed 12-hour restricted entry interval (REI) in accordance with the Worker Protection Standard (WPS).

Review of Human Research This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies, which comprise the Pesticide Handlers Exposur e Database (PHED), and the Outdoor Residential Exposure Task Force (ORETF) Data base, have been determined to require a review of their ethical conduct, have received that review, and have been determined to be ethically conducted.

2.0. HAZARD CHARACTERIZATION

2.1 Hazard Profile

Indaziflam shows low acute toxicity by all rout es of exposure (Toxicity Category III, oral and dermal and Category IV, inhalation) and is not an ocular or dermal irritant or a dermal sensitizer. The database for acute to xicity for indaziflam is complete and is summarized below in Table 2.1a.

An appropriate endpoint for short- or in termediate-term dermal exposure was not identified. No toxicity was observed in a 28-day dermal toxi city study in the rat up to the limit dose of 1000 mg/kg/day. This study is the most relevant study to use since there are no developmental or reproductive c oncerns and the relevant endpoint (neurotoxicity/histopathology of the nervous system) was measured in the dermal study. Therefore, a short- and intermediate-t erm dermal exposure assessment was not conducted.

The short- and intermediate-term incident al oral and inhalatio n no observed adverse effect level (NOAEL) of 7.5 mg /kg/day is based on brain, spin al cord and sciatic nerve degenerative lesions observed at the LOAEL of 15 mg/kg/da y from a subchronic oral dog (gavage) study. The selected endpoint (n eurotoxicity) is the most sensitive NOAEL available from a study of a ppropriate exposure duration (90-days) for short- and intermediate-term exposure. The subchr onic oral dog study was selected over other studies because the dog was the most sens itive species for ne urotoxicity and the subchronic study had the overall lowest NOAEL. Inhalation absorption of 100% is assumed relative to oral absorption because there are no data on inhalation absorption.

Indaziflam is classified as “Not lik ely to be carcinogenic to humans.”

A summary of the toxicologi cal doses and endpoints for occupational and residential exposure scenarios is provided in Table 2.1b . The acute dietary endpoint and dose is provided for assessing episodi c ingestion of granules.

Page 5 of 21

### 2.2 FQPA and Uncertainty Factor Considerations

Although there are no food uses associ ated with the currently proposed uses, HED is reviewing a subsequent submission of proposed food uses. Therefore, the RABII team has considered the postnatal susceptibility of infants and child ren is determined appropriate uncertainty and safety fact ors for the non-food uses. HED recommends reduction of the FQPA safety factor to 1X, ba sed on (1) there is no ev idence of increased quantitative or qualitative pre- and/or postnatal susceptibil ity in a complete database that includes developmental reproductive a nd developmental neurotoxicity, and immunotoxicity studies; (2) developmental effect s in the rat that were observed, but only at high doses and in the presence of matern al/parental toxicity; and (3) selection of endpoints and doses for risk assessments that are protective of potential developmental toxicity.

HED has retained the traditional uncertainty factors for inter-species extrapolation and 10X for intra-species variabilit y. Therefore, HED’s level of concern for residential and occupational handler and posta pplication exposure risk is equal to an MOE of 100. Therefore, scenarios re sulting in MOEs greater than or eq ual to 100 are not of concern to HED.

Table 2.1a Acute Toxicity Profile - Test Substance

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

870.1100 Acute oral - rat 47443281 LD 50 > 2000 mg/kg (both sexes) III

870.1200 Acute dermal - rabbit 47443282 LD 50 > 2000 mg/kg (both sexes) III

870.1300 Acute inhalation - rat 47443283 LC 50 > 2.3 mg/L (both sexes) IV

870.2400 Acute eye irritation - rabbit 47443284 Non-irritant IV

870.2500 Acute dermal irritation - rabbit 47443285 Non-irritant IV

870.2600 Skin sensitization - guinea pig 47443286 Not a sensitizer (Buehler method) N/A



### Page 6 of 21Table 2.1b Summary of Toxicological Doses and Endpoints for Indaziflam for Use in Occupational and Residential Risk Assessments
Exposure/ Scenario Point of Departure (POD) Uncertainty Factors Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (All Populations) NOAEL = 50 mg/kg/day UF A =10X UF H =10X FQPA SF = 1X Occupational & Residential LOC = MOE = 100 Acute oral neurotoxicity in the rat LOAEL = 100 mg/kg/day, based on decreased motor and locomotor activity in females. IncidentalOral ShortTerm (1 to 30 days) andIntermediateTerm (1 to 6 months) NOAEL = 7.5 mg/kg/day UF A =10X UF H =10X FQPA SF = 1X (residential) Occupational & Residential LOC = MOE = 100 Subchronic oral (gavage) in the beagle dog LOAEL = 15 mg/kg/day, based on axonal degenerative microscopic findings in the brain, spinal cord and sciatic nerve.

Dermal (all durations) Not required for this assessment. An appropriate endpoint was not identified for short- or intermediate-term dermal exposure. Long-term dermal exposure is not anticipated.
Inhalation Short-Term (1 to 30 days) andIntermediateTerm (1 to 6 months) NOAEL= 7.5 mg/kg/day. Inhalation absorption assumed to be 100% (default) relative to oral. UF A =10X UF H =10X FQPA SF = 1X (residential) Occupational & Residential LOC = MOE = 100 Subchronic oral (gavage) in the beagle dog LOAEL = 15 mg/kg/day, based on axonal degenerative microscopic findings in the brain, spinal cord and sciatic nerve.

Inhalation Long-Term (> 6 months) Not required for this assessmen t (exposure is seasonal; long-term occupational exposure scenarios are not anticipated).
Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” (under 2005 carcinogenicity guidelines), based lack of treatment-related tumors in the two-year rat and mouse bioassays and no concerns for mutagenicity. Point of Departure (POD) = A data point or an estimate d 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. 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. LO C = level of concern. N/A = not applicable.



### 3.0 PROPOSED USE PATTERNS

Indaziflam is a selective, pre-emergent and post-emergent alkylazine herbicide for control of many annual grasse s and broadleaf weeds in turf (lawns, sod farms, golf courses, recreational fields, et c), ornamentals and trees. It is also proposed for use as a pre-emergent herbicide for weed control in parks, rail roads, utility, industrial and municipal sites. Indaziflam is available for use by commercial and professional applicators (formulated as a water soluble packet and turf fertilizers) as well as residential homeowners (formulated as Lawn 3 FL granules and liquid). It may be applied through a variety of application methods includi ng: ground equipment, right of way handgun, backpack, broadcast and rotary or drop type spreader, hand held equipment (low pressure, high pressure and trigger sprayer) and hose end sprayer. The herbicide requires rainfall or irrigation within several weeks af ter application to activate it and ensure its

Page 7 of 21

### effectiveness. The proposed uses are anticipa ted to result in short- and intermediate-term exposure durations. Table 3 provides a summary of the proposed uses

.

Table 3: Proposed Commercial and Reside ntial Products and Uses of Indaziflam Product EPA Reg. No. Use Site Application Method Application Rate Area Treated Comments

Commercial Products

ground equipment 0.089 lb ai/A 40 acres

right of way 25 acres or 1000 gals handgun 1 acre or 40 gals
low pressure handwand Esplanade 200 SC (Soluble Concentrate) 19% ai 432-xxxx Annual grasses and weeds in non-crop areas (utilities, industrial, municipal and government sites, roadsides) ornamental perennial plantings, around farm buildings, educational facilities, parking lots

back pack 0.089 lb ai/A or 0.0178 lb ai/gal

5 acres or 40 gals Pre-emergent

aerial 1200 acres groundboom 0.125 lb ai/A 200 acres Esplanade F (Flowable Concentrate) 19% ai 432-

xxxx forestry

backpack 0.125 lb ai/A or 0.0248 lb ai /gal 1 acre or (40 gals) Preemergent 1 appliation

groundboom 0.088 lb ai/A 200 acres (forestry) 80 acres (sod farms and Christmas Trees) 40 acres (golf course and field
grown ornamentals)BCSAA10717 20 WSP (Water Soluble Packet) 432-RUOO Annual grasses and weeds in turfgrass, golf courses, sod farms; ornamentals, nurseries, Christmas trees,landscapes forestry, noncrop areas groundboom, hand held equipment 0.071 lb ai/A –
non-crop areas

5 acres (handheld) Single application in spring, summer and fall; 3 month interval between applications; not to exceed 0.088 lb ai/A per year

BCSAA10717 0.0142% Plus Turf Fertilizer (granule) 432-RUOL 80 acres (sodfarm)

40 acres (golf course)BCSAA10717 0.0213% Plus Turf Fertilizer (granule)432- RUOA 10 acres cemeteries

BCSAA10717 0.0284% Plus Turf Fertilizer (granule) 432-RUOT Annual grasses and weeds in turfgrass, (golf courses and sod farms; lawns, cemeteries Tractor-drawn spreader and push type spreader and belly grinder for use on lawns and parks 0.071 lb ai/A

5 acres (parks and commercial lawns) Not to exceed 0.088 lb ai/A per year



### Page 8 of 211 acre (belly grinder) Residential Products Lawn 3FL Concentrate /Ready to
spray 72155-IO Pump style tanksprayer; hoseend sprayerconcentrate; prepacked hose-end ready to spray; low pressure handwand 0.094 lb ai/A 0.5 acres

Lawn 3FL Granule 72155-OR Push type spreader and belly grinder 0.044 lb ai/A 0.5 acres Do not repeat applications within 6 months Lawn 3FL Concentrate Ready to Use 72155-ON Residential lawns, hard scapes and ornamentals

Trigger sprayer 0.00026 lb ai /gal 1 gallon As needed



### 4.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE

4.1 Residential Handler Exposure and Risk

The Agency uses the term “Handlers” to de scribe those individuals who are involved in the pesticide application pro cess. Three indaziflam turf products (i.e., Lawn 3 FL Concentrate/Ready-to-Spray, Lawn 3 FL Gra nule, and Lawn 3 FL Ready-To-Use) can be applied by home owners. These products ar e to be applied using hand held sprayers (pump style tank, hose end, and trigger) or drop/push rotary-type spreaders. The following use scenarios and sources of unit exposures were used to assess handler
exposure:

1. mixer/loader/applicator for garden hose end sprayer (PHED) 2. mixer/loader/applicator for hose e nd sprayer – Mix-Your-Own (ORETF) 3. mixer/loader applicator for belly grinder (PHED) 4. mixer/loader/applicator for hand held pump sprayer (ORETF) 5. mixer/loader/applicator for tr igger sprayer read to use 6. applicator for granular push spreader (ORETF) 7. applicator hose-end ready-to-use sprayer (ORETF)

4.1.1 Turf Data and Assumptions:

Unit Exposures: No chemical specific unit exposure data were provided in support of this submission; therefore, Pesticide Handlers Exposure Database (PHED) Surrogate Exposure Guide and the Outdoor Resident ial Exposure Task Force (OREFT) study (MRID 44972201) unit exposures were used to estimate handler exposure.

Acres/Amount Treated : Information regarding area treated for the various use scenarios was provided by the Science A dvisory Council for Exposure Policy #12:

Page 9 of 21

### Recommended Revisions to the Standard Op erating Procedures (SOPs) for Residnetial Exposure Assessments.

Application Rate and Amount Handled :

 0.094 lb ai per acre for broadcast treatment using liquids

 

### 0.044 lbs ai per acre using granular formulation

 

### 0.00026 lb ai /gal using trigger spray for spot treatment

Exposure Duration: Based on information provided in the proposed labels, handler exposure is anticipated to be short- and intermediate-term in duration.

Body Weight: The average adult body weight of 70 k ilograms was used to assess handler exposure as endpoint wa s not gender specific

. 

### 4.1.2 Residential Turf Handler Exposure and Risk

HED’s level of concern for risks (i.e., Marg ins of Exposure (MOE)) for indaziflam is 100 for residential exposure. Since a short-term dermal point was not se lected, the only route of exposure to be addressed is inhalation. Handler inhalation MO Es were significantly greater than 100 and therefore not of concern to HED. Inhala tion exposure for residential handlers is summarized in Table 4.1.2

.

Table 4.1.2: Indaziflam Handler Exposure and Risk Turf Exposure Scenarios Use Site Inhalation Unit Exposure (mg/lb ) a Application Rate b (lb ai/acre) Area Treated (A/day) Inhalation Dose c (mg/kg/day) MOE d

Mixer/Loader/Applicator Garden Hose End Sprayer (PHED) 72155-IO 0.0095 0. 094 6.38E-6 1,100,000

Hose-end Sprayer “Mix Your Own” (ORETF – OMA004)) 0.017 0.094 1.14E-5 660,000

Belly Grinder (PHED) 72155-OR 0.062 0.044 1.95E-5 380,000

Hand-Held Pump Sprayer(ORETFOMA005) 72155-IO 0.0038 0. 094 0.5

2.55E-6 2,900,000

Trigger
sprayer Ready to Use (ORETF – OMA006) 72155-ON lawns, hardscapes and ornamentals

0.0019 0.00026 lbai/gal 1 gal 7.0E-9 100,000,000

Applicator Granular Push lawns 0.00088 0.044 2.77e-7 27,000,000



### Page 10 of 21Table 4.1.2: Indaziflam Handler Exposure and Risk Turf Exposure Scenarios Use Site Inhalation Unit Exposure (mg/lb ) a Application Rate b (lb ai/acre) Area Treated (A/day) Inhalation MOE d
Dose c (mg/kg/day)

Spreader (ORETF – OMA003) 72155-OR Hose End Sprayer Ready to Use (ORETF – OMA004) 72155-IO lawns, hardscapes and ornamentals 0.011 0. 094 0.5 7.39E-6 1,000,000

a. Inhalation Unit Exposure derived from PHED Versi on 1.1 and ORETF Handler Exposure Study MRID 44972201 b. Application Rate based on proposed labels

c. Inhalation Dose = Unit Exposur e (mg/lb) x Application Rate (lb ai/day) x Area Treated/BW d. Inhalation MOE = NOAEL (7.5 mg/kg/day) Inhalation Dose



### 4.2 Residential Postapplication Exposure

Since a dermal endpoint was not selected th e only postapplication re sidential scenario quantitatively assessed for this action is oral non-dietary ingestion exposures for children (i.e. soil ingestion, and hand-/object-to-mout h). The oral postapplication scenarios resulting from commercial and residential applications were a ssessed using the HED Draft Standard Operating Procedures (SOP ’s) for Residential Exposure Assessments, 2000. Residential postapplication oral exposure and risk resulting in MOEs greater than or equal to 100 are not of concern.

4.2.1 Hand-To-Mouth Assumptions, Exposure, and Risk

This scenario assumes that pesticide residue s are transferred to the skin of children playing on treated areas and are subsequen tly ingested as a result of hand-to-mouth transfer.

Assumptions:

• On the day of application, it may be assumed that 5% of the a pplication rate is available on turf grass as transferable residue.

• Oral postapplication exposure was estimat ed using the standard assumption for the initial fraction of residues available and assuming a 10% daily dissipation rate.

• The median surface area of both hands is 20 cm 2 

### for children.

• It is assumed that there is a one-to- one relationship between the dislodgeable residues on the turf and on the surf ace area of the skin after contact.

• The mean rate of hand-to-mouth activity is 20 times/hour for short-term exposure scenarios.

• The saliva extraction factor is 50%

• The children are assumed to weigh 15 kg

• Duration of exposure for children is a ssumed to be 2 hours per day for turf

Page 11 of 21

### Equations:

TTR t 

### = AR x F x (1-D) t 

### x CF2 x CF3

AR = application rate (lb ai/ft 2 or lb ai/acre or mg ai) F = fraction of ai available on turf (unitless) D = fraction of residue that dissipates daily (unitless) (0.1)
t = postapplication day on which exposure is being assessed CF2 = weight unit conversion factor to convert the lbs ai in the application rate to ug for DFR value (4.54E 8 ug/lb) CF3 = area unit conversion factor to convert the surface area units (ft 2 ) in the application rate to cm 2 for the DFR value (1.08E -3 ft 2 /cm 2 or 2.47E -8 acre/cm 2 ) TTR = Turf Transferable Residue



### PDR = TTR x SA x FQ x ET x SE x CF1 BW

PDR = potential dose rate (mg/day) TTR = turf transferable residue (ug/cm 2 turf) SA = surface area of the hands (cm 2 /event) FQ = frequency of hand-to-mouth activity (20 events/hr for short-term) ET = exposure time (hr/day) CF1 = weight unit conversion factor to convert ug units in the TTR value to mg for the daily exposure (0.001 mg/ug for turf) SE = Saliva Extraction Factor (50%) BW = 15 kg



### Hand-to-Mouth Exposure and Risk

All short-term hand-to-mouth (HTM) scenarios resulted in MOEs greater than the level of concern (MOEs ≥ 100) and therefore pose no risk of concern. Although a quantitative assessment of intermediate-term HTM exposur e was not performed since the short- and intermediate-term endpoints are the same, short-term exposure and risk would be protective of intermediate-term exposure. Table 4.2.1 provides a summary of the shortand intermediate-term HTM exposures.

Table 4.2.1: Hand-To-Mouth Exposure and Risk Product TTR 1 (ug/cm 2 ) SA (cm 2 /event) FQ SE ET (hr/day) CF BW (kg) HTM Dose 2 (mg/kg/day) HTM MOE 3
Commercial Product BCS AA10717 Turf Fertilizer (432-RUOL; 432- RUOA; and 432- RUOT) and 20 WSP (432-RUOO) 3.98E-2 20 20 0.5 2 0.001 15 1.06E-3 7,000

Residential Product Lawn 3FL (72155-IO) 5.27E-2 20 20 0.5 2 0.001 15 1.41E-3 5,300

1. Turf Transferable Residues = (TTR) = AR (0.071 lb ai/A = commercial product; or 0.094 lb ai/A = residential product) x F (0.05) x (1-D) 0 x CF2 (4.54E8 μg/lb) x CF3 (2.47E-8 acre /cm 2 ) = 3.98E-2 or 5.27E-2 ug/cm 2
2. HTM Dose = TTR t x SA x FQ x ET x SE x CF1



### Page 12 of 21BW 3. HTM MOE = NOAEL (7.5 mg/kg/ day)/HTM Dose (mg/kg/day)



### 4.2.2 Object to Mouth (Ingestion of Trea ted Turf) Assumptions and Equations

This scenario estimates doses to toddlers, resu lting from incidental ingestion of pesticide and or residential turf grass that has been pr eviously treated with pesticides. It assumes that pesticide from a treated object or turf is ingested by toddlers who play on treated

areas.

Assumptions:

• On the day of application it may be assume d that 20% of the application rate is available to be ingested.

• Oral postapplication exposure was estimat ed using the standard assumption for the initial fraction of residues availabl e and assuming a 10% dissipation rate.

• Assumed ingestion rate for grass for children (3 years old) is 25 cm 2 

### /day.

• Children are assumed to weigh 15 kg.

Equations:

GR t 

### = AR x F x (1-D) t 

### x CF2 x CF3

GR t = grass residue on day t (ug/cm 2 ) AR = application rate (lb ai/A) F = fraction of ai available on the grass (unitless) D = fraction of residue that dissipates daily (unitless) (0.1)
t = postapplication day on which exposure is being assessed CF2 = weight unit conversion factor to convert the lbs ai in the application rate to μg for grass residue value (4.54E8 μg/lb) CF3 = area unit conversion fact or to convert surface area units (A) in the application
rate to cm 2 for grass residue value (2.47E-8 A/cm 2 )



### PDD = GR t 

### x IgR x CF1

PDD = potential daily dose (mg/kg/day) GR t = grass residue (ug/cm 2 ) IgR = ingestion rate of grass (cm 2 /day) CF1 = weight unit conversion factor to convert the μg of residues on the grass to mg to provide units of mg/day (1E-3 mg/μg 

### )

Object-To-Mouth (OTM) Exposure and Risk

The object-to-mouth scenario resulted in a MO E greater than the level of concern (MOEs ≥ 100) and therefore poses no risk of concern. Table 4.2.2 provides a summary of the OTM exposure and risk.

Page 13 of 21Table 4.2.2: Object–to- Mouth Exposure and Risk Product GR 1 (ug/cm 2 ) CF (mg/μg 

### ) IgR (cm 2 /day) BW (kg) OTM Dose 2 (mg/kg/day) OTM MOE 3

BCS AA10717 Turf Fertilizer (432-RUOL; 432-RUOA; and 432-RUOT) and 20 WSP (432-RUOO) 1.59E-1 0.001 25 15 2.65E-4 28,000

Lawn 3FL (72155-IO) 2.11E-1 0.001 25 15 3.51E-4 21,000

1. GR (grass residue) = Application Rate x F x (1-D) 0 x CF2 x CF3 2. OTM Dose = GR 0 x IgR x CF1 3. OTM MOE = NOAEL (7.5 mg/kg/ day)/OTM Dose (mg/kg/day)



### 4.2.3 Incidental Ingestion of Soil A ssumptions, Exposure and Risk

This scenario assumes pesticide residues in soil are ingested by toddlers who play on treated areas as a result of normal mouthing activities.

Assumptions:

• on the day of application, it is assumed that 100% of the application rate is located within the soil’s uppermost 1 cm.

• Postapplication must be assessed on the same day the pesticide is applied.

• Assumed soil ingestion rate for children is 100 mg/day.

• Children are assumed to weigh 15 kg.

Equations:

SR 0 

### = AR x F x (1-D) t 

### x CF2 x CF3 x CF4

SR 0 = soil residue on day 0 (ug/g) AR = application rate (lb ai/A) F = fraction of ai available in uppermost cm of soil (1 cm) D = fraction of residue that dissipates daily (unitless)
t = postapplication day on which exposure is being assessed (day 0) CF2 = weight unit conversion factor to convert the lbs ai in the application rate to μg for soil residue value (4.54E8 μg/lb) CF3 = area unit conversion fact or to convert surface area units (A) in the application
rate to cm 2 for soil residue value (2.47E-8 A/cm 2 ) CF4 = volume to weight unit conversion factor to convert the volume units (cm 3 ) to weight units for the SR value (0.67 cm 3 /g soil)



### PDD = SR 0 

### x IgR x CF1

PDD = potential daily dose on day 0 SR 0 = soil residue on day 0 (ug/g) IgR = ingestion rate of soil (mg/day) CF1 = weight unit conversion factor to convert the μg of residues on the soil to mg to provide units of mg/day (1E -6 g/μg)



### Page 14 of 21

### Soil Ingestion Exposure and Risk

The soil-ingestion scenario resulted in a MO E much greater than the level of concern (MOEs ≥ 100) and therefore poses no risk of concern. This assessment should be considered conservative in that it assumed no dissipation of soil residues would occur over the exposure period. Table 4.2.3 provides a summary of th e soil ingestion exposure and risk.

Table 4.2.3: Soil Ingestion Exposure and Risk Product SR 1 (ug/g) CF (g/μg 

### ) IgR (mg/day) BW (kg) Dose 2 (mg/kg/day) MOE 3

BCS AA10717 Turf Fertilizer (432-RUOL; 432-RUOA; and 432-RUOT) and 20 WSP (432-RUOO) 5.33E-1 0.000001 25 15 3.56E-6 2.11E6

Lawn 3FL (72155-IO) 7.06E-1 0.000001 25 15 4.71E-6 1.59E6

1. SR 0 (soil residue) = Application Rate (lb ai/A) x F(1) x (1-D) 0 x 0.67 x (4.54x10 8 μg/lg)x (2.47 x 10 -8 A/cm 2 ) 2. Soil Ingestion Dose (mg/kg/day) = SR 0 (μg/g) x IgR (mg/day) x CF1 (g/μg)/BW (kg) 3. Soil Ingestion MOE = NOAEL (7.5 mg/kg/day)/Soil Ingestion Dose (mg/kg/day)



### 4.2.4 Episodic Ingestion of Granules

This scenario was assessed using the Reside ntial SOP and provides a standard method for estimating postapplication doses among toddler s from incidental i ngestion of pesticide granules.

Assumptions and Factors :

• Ingestion rate for dry pesticide formulati on (granules) is 0.3 gram/day for 3 year old child.

• Average weight of toddler is 15 kg.

• Ingestion of granules is c onsidered an episodic event a nd not a routine behavior. Because HED does not believe that this would occur on a regular basis, our concern for human health is related to acute poisoning rather than short -term residue exposure. Therefore and acute dietary dose (NOAEL = 50 mg/kg/day) is used to estimate exposure and risk result ing from episodic inge stion of granules.

Equations and Calculations :

PDD = IgR x F x CF1 ÷ BW

PDD = Potential Daily Dose IgR = ingestion rate of dry pesticide formulation (0.3 grams/day) F = fraction of ai in dry formulation (0.0005) CF = weight unit conversion factor to convert g units to mg for daily exposure (1,000 mg/g) BW = Body Weight (15kg)



### Ingestion of Granules MOE = NOAEL (50 mg/kg/day) ÷ Dose

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### Exposure and Risk

The episodic oral MOE for incidental ingesti on of granules is 5,000 and therefore is not of concern. Table 4.2.4 provides a summary or exposure risk.

Table 4.2.4: Postapplication Exposure and Risk for Incidental Ingestion of Granules

Scenario IgR (g/day) F CF1 (mg/g) Dose a (mg/kg/day) MOE b

Lawn 3FL Granule Reg. No. 72155-OR 0.3 0.0005 1000 0.001 5,000
a. Dose = IgR x F x CF1 ÷ BW b. MOE = acute dietary NOAEL (50 mg/kg/day)/Dose



### 4.3 Combined Residential Risk Estimates

HED combines risk values resulting from se parate exposure scenarios when it is likely they can occur simultaneously based on the use- pattern and the behavior associated with the exposed population. In evaluating combin ed residential uses of indaziflam, HED reviewed all non-dietary sour ces of exposure which consisted of only adult inhalation handler (lawns only) exposure and child posta pplication oral exposures of toddlers. The oral postapplication exposure resulted from hand-to-mouth exposure only, since it represents the worst case of oral exposure. To include exposure from object-to-mouth and soil ingestion in addition to hand-to-mouth could result in a very conservative estimation of exposure as it would overesti mate the potential of oral exposure. A postapplication assessment for adults (homeo wner and golfer) was not performed since there is no dermal endpoint and all uses are outdoors where inhalation exposure is expected to be minimal. Therefore, a combin ed residential assessment is not required. Table 4.3 identifies the residential scenario s and MOEs for adult and children subpopulations simply for use in performing an aggregate exposure assessment in the indaziflam human health risk assessment.

Table 4.3: Combined Resi dential Exposure and Risk Product Use Site Handler Inhalation MOE 1 Post-application Inhalation MOE Hand-to-Mouth MOE 2 MOE

Adult Handler Lawn 3FL Concentrate /Ready to spray 72155-IO Lawns, hardscapes and ornamentals 370,000 NA NA 370,000

Child Postapplication Lawn 3 FL (72155-IO) Lawns, hardscapes and ornamentals NA NA 5,300 5,300

1. See Table 4.1.2: Indaziflam Handler Exposure and Risk 2. See Table 4.2.1 Hand-To-Mouth Exposure and Risk



### Page 16 of 21

### 4.4 Other (Spray Drift, etc)

Spray drift is always a potential source of exposure to resident s nearby to spraying operations. It is noted that the 0.094 lb ai/acre application rate for turf was modeled to estimate postapplication resident ial exposure of children (ages 1 to 6 years of age). As this rate is equal to or higher than many of th e agricultural application rates, this scenario is protective of any exposure of farm children via spray drift from agricultural indaziflam applications.

5.0 OCCUPATIONAL EXPOSURE

The proposed use of indaziflam is for c ontrol of many annual grasses and broadleaf weeds in turf (lawns, sod farms, golf courses, recreational fields, etc), ornamentals and trees. It is also proposed for use as a pre-emergent herbicid e for weed control in parks, rail roads, utility, industrial and municipal sites. Indaziflam is available for use by commercial and professional applicators (formu lated as a water soluble packet and turf fertilizers). Therefore, the potential for occupational handler and postapplication exposure does exist.

5.1 Occupational Handlers

Based upon the proposed use pattern, HED expe cts the most highly exposed occupational pesticide handlers are likely to be:

1) mixing/loading liquids for aer ial applications (PHED); 2) mixing/loading liquids for ground applications (PHED); 3) mixing/loading liquids for ri ght-of-way sprayer (PHED); 4) mixing/loading water soluble packets (PHED); 5) loading granulars of fertilizers using tr actor-drawn granular spreader (PHED); 6) applying sprays via aerial equipment (PHED); 7) applying sprays via groundboom equipment (PHED); 8) applying spray using right- of-way sprayer (PHED); 9) applying granules using solid broadcast spreader (PHED); 10) loading/applying granules by LCO fo r push cyclone spreader (ORETF); 11) loading/applying granules for belly grinder (PHED); 12) flagging for aerial sprays applications (PHED); 13) mixing/loading/applying liquids with low-pressure handwand (PHED); 14) mixing/loading/applying liquids with a backpack sprayer (PHED); and 15) mixing/loading/applying liquids with handgun sprayer (ORETF).

No chemical specific data were available to assess potential exposure to pesticide handlers. The estimates of exposure to pe sticide handlers are ba sed upon surrogate study data available in the PHED (v. 1.1, 1998) and from the Outdoor Residential Exposure Task Force (ORETF). For pe sticide handlers, it is HED st andard practice to present estimates of dermal exposure for “baseline” th at is, for workers wear ing a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves, as well as for “baseline” and the use of prot ective gloves or other

Page 17 of 21

### Personal Protective Equipment (PPE) as might be necessary. The proposed product label involved in this assessment di rects applicators and other ha ndlers to wear long sleeved shirt and long pants, shoes plus sock s, and chemical resistant gloves.

Handler exposure is expected to be short- or intermediate-term in duration based on information provided on proposed labels. In addition, the short- and intermediate-term toxicological endpoints are the same; therefor e, the estimates of risk for short-term duration exposures are protective of those fo r intermediate-term durations. Long-term exposures are not expected; therefore, a long-term assessment was not conducted.

As indicated previously, a derm al endpoint was not selected; therefore, a dermal exposure assessment was not conducted. Daily inhalation handler exposures are estimated for each applicable handler task with the applicati on rate, the area treated in a day, and the applicable inhalation unit exposur e using the following formula:

Daily Exposure (mg ai/day) = Unit Exposu re (mg ai/lb ai handled) x Application Rate (lbs ai/area) x Daily Area Treated (area/day)

Where:

Daily Exposure = Amount (mg or μg ai/day) inhaled that is available for inhalation absorption; Unit Exposure = Unit exposure value (mg or μg ai/lb ai) derived from August 1998 PHED data or from ORETF data; Application Rate = Normalized application rate based on a logical unit treatment, such as acres, square feet, or gallons. Maximum values are generally used (lb ai/A, lb ai/sq ft, lb ai/gal); and Daily Area Treated = Normalized appli cation area based on a logical unit treatment such as acres (A/day), square feet (sq ft/day), gallons per day (gal/day).


### The daily inhalation dose is calculated by normalizing the daily exposure by body weight and adjusting, if necessary, w ith an appropriate dermal or inhalation absorption factor using the following formula:

Average Daily Dose (mg/kg/day) = Daily Ex posure (mg ai/day) x (Absorption Factor (%/100) / Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day); Daily Exposure = Amount (mg ai/day) inhaled that is available for inhalation absorption; Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the lungs (% of the total available absorbed; 100% ); and Body Weight = Body weight determined to represent the population of interest in a risk assessment (70 kg for indaziflam).



### Page 18 of 21

### Inhalation risks for each applic able handler scenario are calculated using a MOE, which is a ratio of the NOAEL or LOAEL to the da ily dose. In the case of indaziflam, a NOAEL was used in the calculation. All MOE values were calculated using the formula below: MOE= NOAEL (mg/kg/day) / Daily Dose (mg/kg/day)

Occupational Handler Exposure and Risk

Table 5.1 presents the estimated risks for workers based on the short- and intermediateterm inhalation exposures at baseline (i.e. no respirator). Short- and intermediate-term risks for handlers are not of con cern (i.e., MOEs are above 100).

Table 5.1. Occupational Handler Inhalation Exposures and Risks

Exposure Scenario and Product Target site Application Rate a Inhalation Unit Exposures (mg/lb ai) Area Treated Daily b Inhalation Doses (mg/kg/day) c Inhalation MOEs d

Mixer/Loader
Liquids for Aerial Applications (PHED) Esplanade F forestry 0.125 lb ai/A 1200 A 0.002571 2900

Liquids for Ground Applications (PHED) Esplanade F forestry 0.125 lb ai/A 0.000429 10,000 200 A

25 A 3.81E-5 196,000 Liquids for Ground , and Right-of-Way, Applications (PHED) Esplanade 200SC non-crop areas, rail road yards, roadsides, ornamental and perennial plantings, fence rows, utilities, hardscapes, industrial, municipal and government site 0.089 lb ai/A Baseline e : 0.0012

40 A 6.1-5 120,000

Non-crop areas, turf

grass, nurseries,

landscapes 5 A 1.22E-6 6,000,000

Golf course and fields grown for

ornamentals 40 A 9.74E-6 770,000

sod farm and , Christmas tree farms 0.071 lb ai/A (non-crop)

80 A 1.95E-5 390,000 Water Soluble Packets Ground Applications (PHED) BCS-AA10717 20 WSP
forestry 0.088 lb ai/A Baseline e 0.00024

200 A 0.000060E-5 120,000

Lawns, recreational

fields and parks 5 A 8.62E-6 870,000

golf course 40 A 6.9E-5 100,000 Loading Granulars for Tractor Drawn Spreader Applications

(PHED) BCS-AA10717 plus turf fertilizer

(0.0142%, 0.0213%, and

0.0284%) sod farm 0.071 lb ai/A Baseline e : 0.0017

80 A 0.000138 54,000



### Page 19 of 21Table 5.1. Occupational Handler Inhalation Exposures and Risks

Exposure Scenario and Product Inhalation Unit Area Inhalation Inhalation Application Target site Rate a Exposures (mg/lb ai) Treated Doses MOEs d Daily b (mg/kg/day) c
Applicators

Applying Sprays via Aerial Equipment

(PHED) forestry 0.125 lb ai/A Esplanade F Eng control f : 0.000068 1200 A 0.000146 51,000

0.125 lb ai/A Esplanade F 0.000264 28,000

forestry 0.088 lb ai/ABCSAA10717

20 WSP 200 A

0.000186 40,000

non-crop areas, rail road yards, roadsides, ornamental and perennial plantings 0.089 lb ai/A Esplanade 200SC 40 A 3.76E-5 200,000

Non-crop sites, turf and recreation fields 5 A 3.75E-6 2,000,000

Golf course and field grown for ornamentals and nurseries 40 A 3.0E-5 250,000 Applying Sprays via Groundboom Equipment

(PHED)

Sod and Christmas tree farms, 0.071 lb ai/ABCSAA10717

20 WSP Baseline e : 0.00074

80 A 6.0E-5 120,000

Applying Sprays via Right-of-Way Equipment

(PHED) non-crop areas, rail road yards, roadsides, ornamental and perennial plantings, fence rows, utilities, hardscapes, industrial, municipal

and government sites, 0.089 lb ai/A Esplanade

200SC Baseline e : 0.0039 25 A 0.000124 60,000

Lawns, turf, sports and recreation parks 5 A 6.09E-6 1,000,000

golf courses 40 A 4087E-5 150,000 Applying Granules using Solid Broadcast Spreader (PHED) sod farms 0.071 lb ai/ABCSAA10717 plus turf fertilizer (0.0142%, 0.0213%, and 0.0284%) 0.0063

80 A 9.74E-5 77,000

Lawns, turf, sports and recreation parks 5 A 3.7E-5 200,000

golf courses 40 A 0.000296 25,000 LCO Push Cyclone Granular Spreader (OMA001)ORETF sod farms 0.071 lb ai/A

0.0073

80 A 0.00532 12,000



### Page 20 of 21Table 5.1. Occupational Handler Inhalation Exposures and Risks

Exposure Scenario and Product Inhalation Unit Area Inhalation Inhalation Application Target site Rate a Exposures (mg/lb ai) Treated Doses MOEs d Daily b (mg/kg/day) c

Belly Grinder (PHED) Lawns, turf, sports and recreation parks 0.062 1 A 6.29E-5 120,000

Flaggers Flagging for Aerial Sprays Applications

(PHED) Esplanade F forestry 0.125 lb ai/A Baseline e : 0.00035 350 A 0.000219 34,000

Mixer/Loader/Applicator 0.125 lb ai/A 5 A 0.000268 28,000 Forestry Esplanade F 0.0248 lb ai/gal 40 gals 0.000425 18,000

0.089 lb ai/A 5 A 0.000191 39,000 Mixing/Loading/ Applying Liquids with Low Pressure

Handwand and

Back Pack

(PHED) non-crop areas, rail road yards, roadsides, ornamental and perennial plantings, fence rows, utilities, hardscapes, industrial, municipal

and government sites Esplanade 200SC 0.0178 lb ai/gal Baseline e : 0.03

40 gals 0.000305 25,000

0.071 BCS-A10717

20 WSP Baseline e : 0.0072 0.0000365 200,000 Mixing/Loading/ Applying Liquid Concentrates with a Handgun Sprayer

(LCO ORETF) Non-crop sites, turf, recreation fields, Christmas tree farms, ornamentals and nurseries 0.089 Esplanade

200SC 0.0018 5 A

0.000014E-5 650,000

a Application rates = maximum application rates from labels. b Amount handled per day values are HED estimates of acr es treated per day based on Exposure SAC SOP #9 “Standard Values for Daily Acres Treated in Agricultu re,” industry sources, and HED estimates. c Dose (mg/kg/day) = Unit exposure(mg/lb ai) x App Rate (l b ai/acre) x Area Treated (acres/day) x %Absorption (100% inhalation) / Body weight (70 kg). d MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day) e Baseline Inhalation: no respirator. f. Eng Con: Engineering control is enclosed cab, or enclosed cockpit.

. 

### 5.2 Occupational/Commercial Postapplication Exposure

HED assumes that inhalation exposures are mi nimal following outdoor applications of an active ingredient, due to the la rge volume of air exchange. Therefore, a quantitative inhalation postapplication risk assessment was not conducte d. Furthermore, since a dermal endpoint was not selected, a pos tapplication exposure assessment was not conducted either. Therefore, the REI will be based on acute toxicity of the technical material, indaziflam. Since indaziflam has low acute toxicity by all routes of exposure (Toxicity Category III, oral and dermal and Ca tegory IV, inhalation) and is not an ocular or dermal irritant or a dermal sensitizer, HED has no objection to the proposed 12-hour restricted entry interval (RE I) in accordance with the WPS.

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