Page 1 of 14 UNITED STATES ENVIRONMENTA L PROTECTION AGENCY WA SHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION DATE: June 7 , 2010 MEMORANDU M SUBJECT: Indaziflam: Occupational and Residential Exposure Assessment for the First

Food Use of the Herbicide on Citrus Fruit, Stone Fruit, Pome Fruit, Grapes, Tree Nuts, Pista c hios and Olives
. PC Code: 080818 DP Number: D 3 76907 Decision No.: 41657 0 Registration Nos.: 264
- xxxx (Indaziflam 200 SC Herbicide and Indaziflam 500 SC Herbicide) Petition Nos: 9F7589, 9E7588 Regulatory Action: Section 3 Registration Assessment Type: Occupational/Residential Case No .: NA TXR No.: NA CAS Number : 950782
- 86
- 2 MRID: NA 40 CFR: NA
FROM: Margarita Collantes, Biologist

Risk Assessment Branch (RAB) II Health Effects Division (7509P) THROUGH: Richard A. Loranger, Ph.D., 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 the Health Effects Divis i on (HED) conduct an exposure and risk assessment fo r proposed uses of the active ingredient indaziflam to control annual grasses and broadleaf weeds in citrus fruit, stone fruit, pome fruit, grapes, tree nuts, pistachios and olives
. Occupational handler and postapplication exposure assessments were conduc ted for the proposed i ndaziflam uses. Residential use patterns are not expected for the proposed uses but have been assessed in a previous memorandum
.Page 2 of 14 TABLE OF CONTENTS
1.0 EXECUTIVE SUMMARY
................................ ................................ ................................ . 3 2.0. HAZARD CHARACTERIZATION
................................ ................................ ................... 4 2.1 Hazard Profile
................................ ................................ ................................ .................. 4 2.2 FQPA and Uncertainty Factor Considerations
................................ ................................ . 5 3.0 PROPOSED USE PATTERNS
................................ ................................ ........................... 7 4.0 RESIDENT IA L (NON
- OCCUPATI ONAL) EXPOSURE
................................ ................. 7 5.0 OCCUPATI ONAL EXPOSURE
................................ ................................ ........................ 9 5.1 Occupational Handlers
................................ ................................ ................................ ... 10 5.2 Occupational Postapplication Exposure
................................ ................................ ......... 13 5.2.1 Postapplication Inhalation Exposure
................................ ................................ ....... 13 5.2.2 Postapplication Dermal Exposure
................................ ................................ ........... 14Page 3 of 14

1.0 EXECUTIVE SUMMARY Indaziflam ([1,3,5
- triazine
- 2,4
- diamine,N
- [(1R , 2S)
- 2,3
- dihydro
- 2,6
- dimethyl
- 1H
- inden
- 1
- yl ]
- 6
- (1
- flu o roethyl)]) is a selective, pre
- emergent and post
- emergent alkyl azine herbicide that controls w eeds b y inhibiting cellulose biosynthesis in plants. The proposed end
- use products evaluated in this assessment include Indaziflam 200 SC Herbicide and Indaziflam 500 SC Herbicide, both formulated as s uspension concentrates containing 19.05% and 45.05 % ind aziflam as the active ingredient, respectivel y. The se products are used as a pre - emergent herbicide for weed control in citrus fruit that have been established for at least one year after transplanting , and in stone fruit, pome fruit, grapes, tree nuts, pi stachios and olives that have been established for at least three ye ars after transplanting. Proposed uses are anticipated to result in short
- and intermediate
- term durations of exposure. Proposed Use Profile For all crops, i ndaziflam may be applied to the soil as a uniform broadcast or band application using ground application equipment only (i.e., ground

boom and hand gun) . Chemigation and aerial applications are prohibited. The maximum single application rate is 0.085 lb ai/A and the maximum annual app lication rate is 0.13 lb ai/A. The minimum retreatment interval is 30 day s (except 90 day s in Florida and Georgia). The pre
- harvest interval is 7 day s for citrus and 14 day s for the other crops. Hazard Characterizatio n Indaziflam shows low acute tox icity by all routes of exposure (Toxicity Category I II, oral and dermal and Category

IV, inhalation) and is not an ocular or dermal irritant or a dermal sensitizer. The point of departure (PoD) selected for regulation of oral, dermal and inhalation risk at all durations is the no observed adverse effect level (NOAEL) of 7.5 mg/kg/day , based on brain, spinal cord and sciatic nerve degenerative lesions observed at the lowest observed adverse effect level (LOAEL) of 15 mg/kg/day from a subchronic oral (gava ge) dog study. Since the dermal PoD was selected from an oral study a 7 .3 % dermal absorption factor was used to estimate dermal exposure. Since the dermal and i nhalation PoDs were the same, margins of exposure (MOEs) were combined to provide a total marg in of exposure for handler exposure scenario s . Indaziflam is classified as “Not likely to be carcinogenic to humans.” FQPA and Uncertainty

Factors HED recommends reduction of the FQPA safety factor to 1X. HED has retained the traditional uncertainty fac tors of 10X for inter
- species extrapolation and 10X for intra
- species variability
. Therefore, HED’s level of concern (LOC) for residential and occupational handler and postapplication risk is equal to a Margin of Exposure ( MOE ) of 100. Scenarios resultin g in MOEs greater than or equal to 100 do not exceed HED ’s level of concern
.Page 4 of 14

Residential Exposure: A residential assessment for use of indaziflam on turf was previously conducted and resulted in no risks of concern. No new residential uses are being req uested at this time. The previous residential assessment resulted in handler and postapplication MOEs ranging from 2,800 to 2,100,000. Occupational Handler Exposure : No chemical specific data were available to assess potential exposure to pesticide handl ers. The estimates of exposure to pesticide handlers are based 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 exposure and risk s re sulted in total MOEs ranging from 3 6 0 to 43,000 and; therefore, do not exceed HED ’s level of concern
. Occupational Postapplication Exposure Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not p erformed for the proposed uses of indaziflam , primarily because it has a very low vapor pressure , it is applied at relatively low application rates (maximum rate is 0.085 lbs ai/A), and it is not projected to be applied via ty picall y high inhalation exposure application equipment (e.g., airblast or aerial equipment). The proposed uses for indaziflam are ground
directed uses where no crop foliage is treated. Currently , HED has no data to assess postapplication dermal exposures to treated soil by occupational workers. In general, such exposures are considered to be negligible. Therefore, for the proposed soil
- directed uses, postapplication exposures and risks to occupational workers were not quantitatively assessed , but are not considered to be of concern
. Restricted Entry

Interval T he restricted entry

interval (REI) is based on the acute toxicity of indaziflam technical material. Active ingredients classified as category III or IV for acute dermal toxicity , eye irritation potential, and skin irritation p otential are assigned a default REI of 12 hours under the Worker Protection Standard for Agricultural Pesticides
. Based on the acute toxicity profile of indaziflam, the 12
- hour REIwhich appears on the proposed labels is adequate
. Review of Human Researc h 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 Exposure Database (PHED), and the Outdoor Residentia l Exposure Task Force (ORETF) Database, have been determined to require a review of their ethical conduct, have received that review, and have been determined to be ethicall y conducted.
2.0. HAZARD CHARACTERIZATION 2. 1 Hazard Profile Indaziflam shows low acute toxicity by all routes of exposure (Toxicity Category I II, oral and dermal and Category

IV, inhalation) and is not an ocular or dermal irritant or a dermal sensitizer. The database for acute toxicity for indaziflam is complete and is summarized below in TablePage 5 of 14

2.1a. The short
- and intermediate
- term incidental dermal and inhalation no observed adverse effect level (NOAE L) of 7.5 mg/kg/day is based on brain, spinal cord and sciatic nerve degenerative lesions observed at the LOAEL of 15 mg/kg/day from a subchronic oral (gavage) dog study
. Since the dermal PoD was selected from an oral study , a 7 .3 % dermal absorption factor was used to estimate human dermal absorption. Since no inhal ation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (i.e., 100% inhalation absorption is assumed)
. T he dermal and inhalation PoDs were the same; there fore, margins of exposure (MOEs) were combined to provide a total margin of exposure for handler exposure scenarios. The selected PoD (neurotoxicity ) is the most sensitive NOAEL available from a study of appropriate exposure duration (90
- day s) for short
- and intermediate
- term exposure. The subchronic oral dog study was selected over other studies because the dog was the most sensitive species for neurotoxicity

and the subchronic study had the overall lowest NOAEL. Although a 28
- day dermal toxicity

study in the rat showed no effects at the limit dose (including neuropathology), it was not selected as a PoD for the dermal exposure scenario due to the significantl y greater sensitivity for neurotoxicity

seen in the dog relative to the rat. Neurotoxic effects in the dog were identified at doses that were 10
- 20 times lower than in the rat. The PoD is nonetheless considered conservative because the effects in the dog were observed following gavage dosing, in contrast to a relativel y slower dermal absorption rat e expected for occupational exposure . Indaziflam is classified as “Not likely to be carcinogenic to humans.” A summary

of the toxicological doses and PoDs for occupational exposure scenarios is provided in Table 2.1b
. 2.2 FQ PA and Uncertainty Fact or Considerations HED recommends reduction of the FQPA safety factor to 1X. The toxicity database for indaziflam is complete, including the required studies that characterize potential susceptibility of infants and children. There was no evidence of increased quantitative or qualitative pre
- and/or postnatal susceptibility ; developmental effects in the rat were observed only at high doses in the presence of maternal/parental toxicity . Although indaziflam causes neurotoxicity , the effects are well charact erized and served as the basis for endpoint selection. Therefore, the risk assessment is protective of potential neurotoxicity and other effects which occurred at higher doses. HED has retained the traditional uncertainty factors of 1 0X for inter
- speci es extrapolation and 10X for intra
- species variability . Therefore, HED’s level of concern (LOC) for residential and occupational handler and postapplication exposure is an MOE of 100. Therefore, scenarios resulting in MOEs greater than or equal to 100 do not exceed HED’s level of concern.Page 6 of 14

Table 2.1a Acute Toxicity Profile - Indaziflam Guideline No. Study T ype MRID(s) Results Toxicity Category 870.1100 Ac ute oral
- rat 47443281 LD 50 > 2000 mg/kg (both sexes) III 870.1200 Ac ute dermal
- rabbit 474432 82 LD 50 > 2000 mg/kg (both sexes) III 870.1300 Ac ute inhalation
- rat 47443283 LC 50 > 2.3 mg/L (both sexes) IV 870.2400 Ac ute eye irritation
- rabbit 47443284 Non
- irritant IV 870.2500 Ac ute dermal irritation
- rabbit 47443285 Non
- irritant IV 870.2600 S kin sensitization
- guinea pig 47443286 Not a sensitizer (Buehler method) N/A
Table 2.1b Summary of Toxicological Doses and Points of Departure for Indaziflamfor Use in Occupational and Residential Risk Assessments Exposure/ Scenario Point of Departure

(P o D) Uncertainty

Factors Level of Concern

for Risk Assessment Study and Toxicological Effects Incidental Oral Short
- Term

(1 to 30 days) and Intermediate
Term (1 to 6 mo nths) 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 dog

LOAEL = 15 mg/kg/day, based on axonal degenerative microscopic findings in the brain, spinal cord and sciatic nerve. Dermal Short
Term (1 to 30 days) and Intermediate
term (1 to 6 mo nths) NOAEL = 7.5

mg/kg/day DAF = 7.3% UF A=10X

UF H =10X FQPA SF = 1X (residential) Occupational &

Residential LOC MOE = 100 Subchronic oral (gavage) in the dog

LOAEL = 15 mg/kg/day, based on axonal degenerative microscopic findings in the brain, spinal cord and s ciatic nerve. Dermal, Long
Term (>6 mo nths) Not required for this assessment (exposure is seasonal; long
- term occupational exposure scenarios are not anticipated). Inhalation Short
- Term

(1 to 30 days) and Intermediate
Term (1 to 6 mo nths) 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 dog

LOAEL = 15 mg/kg/day, based on axonal degenerative micros copic findings in the brain, spinal cord and sciatic nerve. Inhalation Long
- Term

(> 6 months) Not required for this assessment (exposure is seasonal; long
- term occupational exposure scenarios are not anticipated). Cancer (oral, dermal, inhalation) Classi fication: “Not likely to be Carcinogenic to Humans” Point of Departure (P o D) = A data point or an estimated point that is derived from observed dose
- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation inPage 7 of 14

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
3.0 PROPOSED USE PATTERNS Table 3 provides a summary of the proposed uses of indaziflam
. The proposed product label involve d in this assessment directs handlers to wear long sleeved shirt and long pants, shoes plus socks, and chemical resistant gloves. Table 3: Proposed Uses of Indaziflam Product Use Site Target of Application Treatment

Ty pe Application Method Maximum

Appli cation Rate Comments
Indaziflam 200 SC Herbicide (5.0 to 6.5 fl oz product/A) 1.67 lbs a.i./gal and Indaziflam 500 SC Herbicide (2.0 to 2.6 fl o z product/A) 4.16 lbs a.i./gal (EPA Reg. 264
- xxxx) Citrus

Fruit, Stone Fruit, Pome Fruit, Grapes, Trees Nuts, Pistachios, Olives Soil

(preemergence control of annual grasses and broadleaf weeds) Broadcast

and band application Groundboom,

handgun 0.085 lb

ai/A per application Only apply to citru s trees that

have been established for at least one year after transplanting
. Only apply to all other labeled tree and vine crops that have b een established for at least three year s after transplanting
. Retreatment Interval : 30 day s (except 90 days in FL and GA) P reharvest I nterval : 7 day s for citrus, 14 days for other crops Maximum annual application rate is 0.13 lb ai/A
. Do not apply by chemigation or air
.
4.0 RESIDENTIAL (NON - OCCUPATIONAL) EXPOSURE A residential assessment for use of indaziflam on turf was previously conducted in D372538 (M. Collantes; 4/2 1/10). No new residential uses are being requested at this time
. Handler MOEs were significantly

greater than 100 (ranging from 3,000 to 510,000) and are not of concern. Dermal postapplication exposures were assessed for adults and children. Additi onally, oral non
dietary ingestion exposures were assessed for children (i.e. soil ingestion, and hand
- /object
- to mouth). The postapplication scenarios resulting from commercial and residential applications were assessed using the HED Draft Standard Operating Procedures (SOP’s) for Residential Exposure Assessments, 2000
. All adult and children residential lawn and golf dermal scenarios resulted in MOEs greater than the level of concern (ranging from 2,800 to 90,000) for short
- termPage 8 of 14

exposure and are not of concern to HED. Since the short
- and intermediate
- term dermal endpoints are the same, onl y short
- term dermal exposures were assessed for adults and children. HED estimates short
- term dermal postapplication exposure based on day
- 0 residues. Using day
- 0 residues to assess intermediate
term exposure does not take into account dissipation of residues over time and thus results in a conservative estimation. Therefore, the short
- term dermal postapplication exposure assessment represents the worst case scenario and is protective of intermediate
- term dermal exposure. All short
- term hand
- to - mouth (HTM), object
- to - mouth (OTM) and soil ingestion scenarios resulted in MOEs ranging from 5,300 to 2,100,000; therefore, these exposures pose no risk of concern to HED. Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for the proposed uses of indaziflam at this time primarily because it has a very

low vapor pressure (vapor pressure less than 5 x 10 - 10 mmHg at 25oC), it is applied at low application rates (maximum rate is 0.085 lbs ai/A), and it is not projected to be applied via ty picall y high inhalation exposure application equipment (e.g., airblast or aerial equipment). However, volatilizatio n of pesticides may be a potential source of postapplication inhalation exposure to individuals nearb y to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fun gicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, t he Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for indaziflam. 4.1 Spray Drift Spray drift is a potential source of exposure for residents living in close proximity to spraying operations. This situation is particularl y the case with aerial application. However, to a lesser extent, spray

drift resulting from the ground application of indazi f lam could also be a potential source of exposure. The Agency has been working with the Spray Drift Task Force (a m embership of US pesticide registrants), EPA Regional Offices, State Lead Agencies for pesticide regulation, and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by

the Spray

Drift Task Force, and is developing a policy on how to appropriatel y apply the data and the AgDRIFT computer model to i ts risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off
- target drift, and risks associated with pesticide application.Page 9 of 14

Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. It is noted that the 0.094 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure o f children (ages 1 to 6 ye ars of age) . As this rate is equal to or higher than many of the commercial application rates, this scenario is protective of any exposure of children via spray drift from commercial indaziflam applications. 4. 2 Combined Residential Exposure : HED combines risk values resulting from separate exposure scenarios when it is likely they can occur simultaneousl y based on the use
- pattern and the behavior associated with the exposed population. HED evaluated the following combine d residential uses of indaziflam, 1.) adult dermal and inhalation handler (lawns onl y) exposure, and 2.) child postapplication dermal and oral exposures. Since HED generally does not combine adult handler and dermal postapplication exposure, such a combin ed quantitative residential exposure estimate was not provided. However, combined residential scenario assessments for children which could occur simultaneously

were performed and did not result in risks of concern. Table 4. 2 : Combined Residential Exp osure and Risk Product Use Site Handler Total MOE 1 Post - application

Derm al MOE 2 Hand - to - Mouth

MOE 3 Combined

MOE 4 Adult Lawn 3FL Concentrate /Ready to spray 72155
- IO Lawns, hardscapes and ornamentals 3,000 4,700 NA NA

Child Lawn 3 FL (72155
- IO) Lawns, hardscapes and ornamentals NA 2,800 5,300 1,800
1. See Table 4.1.2: Indaziflam Residential Handler Exposure and Risk (Hand Held Pump) ; D372538; 4/21/10 2. See Table 4.2.2b Dermal Postapplication Exposure and Risk (DFR data) ; D372538; 4/21/10 3. See Table 4.2.3 Hand
- To
- Mouth Exposure and Risk ; D372538; 4/21/10 4. Adult Combined MOE = NA = HED does not combine adult handler and postapplication exposure Child Combined MOE = NOAEL (7.5 mg/kg/day)/dermal postapplication dose (0.00266) + HTM dose (0.00141) HED did not combine risk resulting from adult homeowner handler, postapplication and golfer exposure to treated turf because HED considers the probability of co
- oc c urre nce for these scenarios to be low
. 5.0 OCCUPATIONAL EXPOSURE The proposed uses of indaziflam are for control of annual grasses and broadleaf weeds in citrus fruit, stone fruit, pome fruit, grapes, tree nuts, pistachios and olives. This document assesses occupational exposures and risks from the proposed uses of Indaziflam 200 SC Herbicide (suspension concentrate, 19.05% ai , 1.67 lb ai/gal ) and Indaziflam 500 SC Herbicide (suspension concentrate, 45.05% ai, 4.16 lb ai/gal ).Page 10 of 14

5.1 Occupational Handlers The quantitative exposure/risk assessment for occupational handlers is based on the following exposure scenarios , which are considered to be the most highly exposed scenarios by

HED : 1) mixing/loading liquids for ground boom applications (PHED); 2) applying spray s using groundboom equipm ent (PHED); and 3) mixing/loading/appl yi ng liquids with handgun sprayer (ORETF). Unit Exposures: No chemical specific data were available to assess potential exposure to pesticide handlers. The estimates of exposure to pesticide handlers are based upon sur rogate study data available in the PHED (v. 1.1, 1998) and from the Outdoor Residential Exposure Task Force (ORETF). The ORETF data were designed to replace the present PHED data with higher
- confidence, higher quality data that contain more replicates than the PHED data for those scenarios. In this assessment, ORETF data w ere used to assess mixing/loading/appl yi ng with handgun equipment (data from MRID 44972201). Mitigation Approaches: For pesticide handlers, it is HED standard practice to present estimates of dermal and inhalation exposure for “baseline , ” i.e., a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves and no respirator. If further exposure mitigation is needed to achieve an MOE greater than the LOC , then personal protective equipment (such as chemical
- resistant gloves, double layer body protection and/or respirators) or engineering controls may be considered. The proposed product label involved in this assessment directs handlers to wear long sleeved shirt and long pants, shoes plus socks, and chemical resistant gloves. Exposure Duration: Although, h andler exposure is expected to be short
- or intermediate
- term in duration based on information provided on proposed labels , intermediate
- term exposure is considered to be less likely
. In addition, the short
- and intermediate
- term toxicological PoDs are the same; therefore, the estimates of risk for short
- term duration exposures are protective of those for intermediate
term durations. Long
- term exposures are not expected; therefore, a long
- term assessment was not conducted. Application Rate: The proposed maximum application for all crops is 0.0 8 5 lb ai/A
. Area Treated: The area treated in a day

is base d on HED Exposure Science Advisory Committee SOP No. 9.1 and professional judgment
. An area of 80 acres per day was assumed for mixing/loading and applying using groundboom equipment and an area of 25 acres per day was assumed for mixing/loading/appl yi ng using handgun equipment mounted on motorized vehicle
.Page 11 of 14

Body Weight: The average adult body

weight of 70 kg was used for estimating dermal and inhalation dose, since the selected toxicological PoDs are not sex - specific. Absorption Factor s : Since the short
- and intermediate
- term dermal PoD was based on an oral study , a dermal absorption factor of 7. 3 percent was used to estimate dermal exposure for short
- and intermediate
term durations. Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure (i.e
. , 100% inhalation absorption is assumed). Equations and Calculations: Daily handler exposures are estimated for each applicable handler task with the application rate, the area treated in a day , and the applicable dermal and inhalation unit exposure using the following formula: Daily Exposure: Daily

handler exposures are estimated for each applicable handler task with the application rate, the amount of acres treated in a day , and the applicable unit exposure using the following formula: Daily Exposure (mg ai/day) = Unit Exposure (μg ai/lb ai handled) * Application Rate (lbs ai/A) * Daily Amount Handled (lbs/day) * Conversion Factor (mg/1,000 μg) Where: Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption, Unit Exposure = Unit exposure value (μg ai/day), Application Rate= Normalized application rate based on a logical unit treatment, such as acres; maximum values are used (lb ai/A), and Daily Amount Handled = Normalized application area based on a logical unit treatment such as acres (A/day). Daily Dose: Daily

dose (inhalation or dermal) was calculated b y normalizing the daily dermal or inhalation exposure value by body weight and accounting for dermal and i nhalation absorption. Average Daily Dose (mg/kg/day) = Daily Exposure (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) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption, Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the skin or lungs, andPage 12 of 14 Body Weight = Body w eight determined to represent the population of interest in a risk assessment. Margin of Exposure (MOE): The dail y dermal dose and dail y inhalation dose received b y occupational handlers w ere compared to the appropriate point of departure (i.e ., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values were calculated separately for dermal and inhalation exposure levels using the following formula: MOE = NOAEL (mg/kg/day)

Average Daily Dose (mg/kg/day) Where: MOE = Margin of exposure value used by HED to represent risk or how close a chemical exposure is to being a concern (unitless), ADD = Average daily dose (ADD) is absorbed dose received from exposure to

pestic ide, and NOAEL = Dose level in a toxicity study, where no observed adverse effects occurred in the

study. Combined Risks: Dermal and inhalation risks for short
- and intermediate
- term exposures were combined in this assessment, since the toxicologi cal effects for the dermal and inhalations routes were the same. Dermal and inhalation risks were combined to determine a total MOE using the following formula:

Total MOE = 1/ ((1/ Dermal MOE) + (1/Inhalation MOE)) Handlers Exposure and Risk : Summaries of the risks for occupational handlers are included in Table 5.1 . The results of the occupational handler exposure and risk assessment indicate that short
- and intermediate
- term dermal, inhalation and total MOEs were greater than the level of concern (MOEs ≥ 100) at the baseline clothing level ( i.e. single layer clothing and no respirator), when baseline data are available. There are no baseline dermal data to ass ess the mixing/loading/applying handgun scenario. The proposed product label involved in this assessment directs handlers to wear long sleeved shirt and long pants, shoes plus socks, and chemical resistant gloves. When baseline attire plus chemical
- resistant gloves are used for this scenario, short
- and intermediate
- term dermal and total MOEs were greater than th e level of concern (MOEs ≥ 100).Page 13 of 14

Table 5.1. Occupational Handler Exposures and Risks a Exposure Scenario Crop or Target App
. Rate b (lb ai/A) Area Treated Dailyc (acres) Unit Exposure d Dose e (μg/kg/day) MOE f, g Dermal (mg/lb ai) Inhalatio n

( m g/lb ai) Dermal Inhalation Dermal Inhalation Total Mixer/Loader Groundboom Equipment (PHED data) Citrus Fruit, Pome

Fruit, Stone Fruit, Grapes, Tree Nuts, Pistachios, Olives 0.085 80 2.9 0.0012 0.021 0.0001 16 3 6 0 6 5 , 000 3 6 0 Applicator Groundbo om Equipment (PHED data) Citrus Fruit, Pome

Fruit, Stone Fruit, Grapes, Tree Nuts, Pistachios, Olives 0.085 80 0.014 0. 000 74 0.000099 0.000072 76 , 000 100 , 000 4 3 , 000
Mixer/Loader/Applicator Handgun Sprayer (ORETF data) Citrus Fruit, Pome

Fruit, Stone Frui t, Grapes, Tree Nuts, Pistachios, Olives 0.085 2 5 0.45 (with gloves) 0.00 18 0.001 (with gloves) 0.000055 7, 5 00

(with gloves) 140,000 7, 1 00

(with gloves)
a . Risks represent baseline attire ( l ong - sleeve shirt, long pants, no respirator), except where indicate d (i.e. addition of chemical
- resistant gloves for the mixer/loader/applicator handgun scenario). b
. Application rates = maximum application rates from labels. c . Amount handled per day values are HED estimates of acres treated per day based on Exposur e SAC SOP #9 .1 “Standard Values for Dai ly Acres Treated in Agriculture ” and professional judgement. d. Unit Exposures based on PHED Version 1.1 or ORETF data. e . Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/acre) x Area Treated (acres/d ay) x % Absorption (7.3% dermal and 100% inhalation) / Body weight (70 kg). f
. Dermal and Inhalation MOE = NOAEL (7.5 mg/kg/day) / Dose (mg/kg/day) g . Total MOE = 1 / (1/ Dermal MOE) + (1/ Inhalation MOE). 5.2 Occupational Postap plication Exposure 5.2.1 Postapplicati o n Inhalation Exposure Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for the proposed uses of indaziflam at this time primarily because it ha s a very

low vapor pressure (vapor pressure less than 5 x 10 - 10 mmHg at 25oC ) , it is applied at low application rates (maximum rate is 0.085 lbs ai/A), and it is not projected to be applied via ty picall y high inhalation exposure application equipment (e.g. , airblast or aerial equipment). However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearb y to pesticide applications. The Agency sought expert advice and input on issues related to volati lization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for indaziflam.Page 14 of 14

5.2.2 Postapplication Dermal Exposure The proposed uses for indaziflam are ground
- dire cted uses where no crop foliage is treated. Currently , HED has no data to assess postapplication dermal exposures to treated soil by occupational workers. In general, such exposures are considered to be negligible. Therefore, for the proposed soil
- direct ed uses, postapplication exposures and risks to occupational workers were not quantitativel y assessed , but are not considered to be of concern
. Restricted Entry Interval T he restricted entry

interval (REI) is based on the acute toxicity of indaziflam technical material. Active ingredients classified as category III or IV for acute dermal toxicity , eye irritation potential, and skin irritation potential are assigned a default REI of 12 hours under the Worker Protection Standard for Agricultural Pestic ides
. Based on the acute toxicity profile of indaziflam, the 12
- hour REIwhich appears on the proposed labels is adequate
.