Page 1 of 17 

### UNITED STATES ENVIRONMENTAL PROTECTI ON AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES 

### MEMORANDUM D ATE : 9 /23 /09 SUBJECT: Spirodiclofen : Occupational and Residential Exposure/Risk Assessment for th e

Tropical Fruit Subgroup PC Code: 12 4871 DP Barcode: D 36 3346 Decision No.: 404 221 Registration No. : 264
- 83 1 Petition No.: 8F7500 Regulatory Action: Section 3 Registrations Risk Assessment Type: ORE Case No.: NA T XR No.: NA CAS No.: 148477
- 71
- 8 MRID No.: 456973
- 13 40 CFR: §180.566 FROM: Lata Venkateshwara, Environmental Scientist

Health Effects Division/Risk Assessment Branch 1 (7509P) THROUGH: Kelly

M. Lowe, Environmental Scientist Dana Vogel, Branch Chief Health Effects Division/Risk Assessment Branch 1 (7509P) TO: Rita Kumar , PM (11)

R egistration Division Introduction The registrant, Baye r CropScience , has requested registration of the miticide spirodiclofen for use on the tropical fruit subgroup (avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla and star apple)
. Baye r CropScience have requested these crops be added to the end use product , ENVIDOR® 

### 2 SC Miticide (EPA Reg. No 264
- 831). N o residential uses are being requested at this time. This memorandum only addresses risk from occupational exposure to the proposed new uses of spirodiclofen . An aggregate human risk assessment for these new uses is presented in a separate Health Effects Division (HED) memorandum.Page 2 of 17 

### TABLE OF CONTENTS 1.0 Executive Summary
................................ ................................ ................................ .............. 3 2.0 Hazard Profile
................................ ................................ ................................ ....................... 4 3.0 Use Profile
................................ ................................ ................................ ............................ 6 4.0 Occupational Exposure
................................ ................................ ................................ ......... 6 4.1 Short and Intermediate Term Non
- Cancer Exposures
................................ .................... 6 4.1.1 Occupational Handler Exposure and Risk
................................ ................................ .. 6 4.1.2 Occupational Postapplication Exposure and Risk
................................ .................... 10 4.2 Cancer Exposures
................................ ................................ ................................ .......... 12 4.2.1 Occupational Handler Cancer Exposure and Risk
................................ .................... 12 4.2.2 Occupational Postapplication Cancer Exposure and Risk
................................ ........ 15 5.0 Non
- Occupational/Residential Exposure
................................ ................................ ................ 16 6.0 Non
- Occupational Off
- Target Exposure
................................ ................................ ............. 16Page 3 of 17



### 1.0 Executive Summary This document presents an occupational exposure/risk assessment of new spirodiclofen uses . The formulated end
- use product for the proposed crop uses are labeled under the trade name: ENV IDOR ® 

### 2 SC Miticide. Hazard Profile In the 2008 risk assessment (Memo, M. Clock
- Rust, 01
- Apr
- 08, DP339672), the Agency identified short
- term dermal and inhalation endpoints based on a subchronic oral toxicity study in dogs. For i ntermediate
- and long
- term dermal and inhalation risk assessments, a chronic oral toxicity study in dogs was selected. An oral study was selected because the endpoint of concern (i.e., adrenal, testes, etc.) was not measured in the 28
- day dermal toxicity study
. A dermal
- absorption factor of 2% is used for all dermal exposure assessments since dermal endpoints are from an oral study . The dermal absorption factor is based on a primate dermal
absorption study
. In the absence of an available 21/28 day inh alation study toxicity

by the inhalation route is considered to be equivalent to the toxicity by the oral route of exposure
. The HED Cancer Assessment Review Committee (CARC ) classified spirodiclofen as “Likely to be Carcinogenic to Humans” and assigned a Q 1 * 

### (mg/kg/day) - 1 

### of 1.49 x 10 - 2 

### in human equivalents based on male testes Leydig cell adenoma. Therefore, a low
- dose extrapolations method was used for human cancer risk assessment
. The level of concern (LOC) for short
- term dermal and inhalation scenarios is 300 and the LOC for intermediate and long
- term scenarios is 100. Use Profile Spirodiclofen is part of a new class of chemicals called tetronic acid insecticides. Tectronic acids are primaril y acaricides with insecticidal uses at higher doses. Th e mode of action occurs through the inhibition of lipid biosy nthesis, which inhibits the ability to develop through the various mite growth stages and the ability to reproduce in adults. Spirodiclofen is structurall y similar to spiromesifen, which is also a tetronic acid insecticide. Spirodiclofen is currently registered for use on grapes, citrus fruits, pome fruits, stone fruits , tree nuts , Christmas tree plantations, and hops . There are no registered or proposed residential uses. Spirodiclofen is prop osed b y Bayer CropScience for used in a 0 .28
- 0.31 lb active ingredient (ai)/ acre soluble concentrate (ENVIDOR ® 

### SC Miticide) on avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla and star apple. Occupational Exposure/

Risk No chemi cal
- specific handler exposure data were submitted in support of this Section 3 registration. It is the policy of the HED to use data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in PHED Surrogate Exposure Guide (8/98) to a ssess handler exposures for regulatory actions when chemical
- specific monitoring data are not available (HED Science Advisory Council for Exposure (ExpoSAC) Draft SOP # 7, datedPage 4 of 17



### 1/28/99). Handler and post
- application exposure is expected to be short
- term based on information provided on proposed labels (e.g., onl y one application allowed per crop season)
. A irblast and aerial applications were assessed. All short
- term risks for occupational handlers do not exceed HED's level of concern (i.e., MOE s ≥ 300 ) at baseline except for aerial handler which was with engineering controls. All post
- application risks are also not of concern (i.e. , MOEs ≥ 300). The proposed label for ENVIDOR ® 

### has a 12
- hour restricted entry interval (REI). Spirodiclofen is classified as Toxicity Category I I I for acute oral and acute dermal toxicity ; and Toxicity Category IV for acute inhalation, primary eye irritation and primary dermal irritation. It is a dermal sensitizer. Under the conditions described herein (i.e., reg arding hazard identification and application practices), the interim worker protection standard (WPS) REIof 12 hours is adequate to protect agricultural worker from post
- application exposures. Residential Exposure/Risk Spirodiclofen is not proposed or registe re d for any residential uses
. Review of Human Research This risk assessment relies in part on data from Pesticide Handlers Exposure Database (PHED) studies in which adult human subjects were intentionally exposed to a pesticide or other chemical . These studies have been reviewed and have been determined to be ethical. 2.0 Hazard Profile The toxicological factors used in this assessment are taken from: Memo, M. Clock
- Rust, 01
- Apr
- 08, DP339672, “Human
- Health Risk Assessment for Spirodiclofen fo r Use on Hops.” The acute toxicity

categories for spi rodiclofen are summarized in Table 1 . The doses selected for this risk assessment are summarized in Table 2. In the 2008 risk assessment, the Agency identified a short
- term duration dermal toxicological endpoint from a subchronic oral toxicity study in the dog. The point of departure (POD) i s the Lowest Observable Adverse Effect Level (LOAEL), 8.4 mg/kg/day . The toxic effects noted were increased adrenal gland weight which corroborated with histopatho logy finding s (cy toplasmic vacuoles in the Zona fasciculata of the adrenals). A dermal absorption rate of 2% was identified to extrapolate dermal exposure from oral study data. The level of concern is an uncertainty factor (UF) of 300 ( i.e., 10X for intraspecies variation, 10X for interspecies variation and 3X for use of a LOAELv ersus a No Observable Adverse Effect Level (NOAEL) )
. The short
- term duration inhalation toxicological endpoint is the same as identified (above) for short
- term duration dermal exposures. It is identified from the same subchronic feeding study in the dog. The toxic effects are the same as noted above. Since no inhalation absorption data are available, toxicity

by the inhalation route is considered to be equivalent to toxicity by the oralPage 5 of 17



### route of exposure. The level of concern is for MOEs < 300. The HED Cancer Assessment Review Committee (CARC) met on 5 May 2004 to discuss the carcinogenic potential of spirodiclofen (Memo, L. Brunsman, TXR NO. 0052535, “Spirodiclofen Quant itative Risk Assessment (Q 1 * 

### ) Based on Wistar Rat and CD
- 1 Mouse Dietary Studies with 3/4's Interspecies Scaling Factor”, 6 May 2004). The CARC classified spirodiclofen as “Likel y to be Carcinogenic to Humans” and assigned a Q 1 * 

### value of 1.49 x 10 - 2 

### mg a. i./kg bw/day
. Therefore, a low
- dose extrapolation method was used for human cancer risk assessment
. Quantification of cancer risk used a Q 1 * 

### (mg/kg/day) - 1 

### of 1.49 x 10 - 2 

### in human equivalents based on male rat testes Leydig cell adenoma. Spirodiclofen i s classified as Toxicity Category III for acute oral and acute dermal toxicity ; and Toxicity Category IV for acute inhalation, primary eye irritation and primary dermal irritation. It is a dermal sensitizer. Table 1. Acute Toxicity Profile for Spirod iclofen OPPTS Guideline Study Type Results Toxicity Category 870.1100 Ac ute oral toxicity / rat LD 50 => 2000 mg/kg (males and females) III 870.1200 Ac ute dermal toxicity / rat LD 50 => 2000 mg/kg (males and females) III 870.1300 Ac ute inhal ation toxicity / rat LC 50 => 5.03 mg/L (males and females) IV 870.2400 Primary eye irritation / rabbit Non
- irritating IV 870.2500 Primary dermal irritation / rabbit Non
- irritating IV 870.2600 Dermal sensitization / guinea pig Sensitizer

–Page 6 of 17



### Table 2 . Summary of Toxicology Endpoint Selection for Spirodiclofen for These Specific Uses Exposure Scenario Dose Used in Risk

Assessment, UF FQPA SF and Level

of Concern for Risk Assessment Study and Toxicological Effects Short
- t e rm

Incidental Oral ; Short
- term

Dermal; Short
- term

Inhalation (1
- 30 Days) LOAEL = 8.4 mg/kg/day ( dermal
- absorption rate= 2%) Occupational LOC for MOE = 300 Subchronic Oral Toxicity Study in Dogs LOAEL= 8.4 mg/kg/day based on increased adrenal gland weight (two out of four animals) which corroborated with histopathology findings (cytoplasmic vacuoles in the Zona fasciculata of the adrenal glands) in females; a NOAEL for females was not established. Long
- term

Dermal; Long
- term

Inhalation (>6 Months) Oral NOAEL= 1.38 mg/kg/day ( dermal
- absorption rate = 2%) Occupational LOC for MOE = 100 Chronic Oral Toxicity Study in Dogs See above under Chronic Dietary
.
Cancer (Oral, dermal, inhalation) Classification: “Likely to be Carcinogenic to Humans” with Q 1 * (mg/kg/day) - 1 = 1.49 x 10 - 2

. 

### 3.0 Use Profile Table 3 summarizes the proposed use pattern and formulation specified in the end
- use product containing spirodiclofen . The label directions for ENVIDOR® 2 SC Miticide (EPA Reg. No. 264
- 831 ) recommend a maximum application rate of 2 0 fluid ounces per acre or 0.31 lb ai/A for avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla, and star apple. The label does not provide an application interval and states to apply no more than one application per crop season.

Table 3 . Summary of Proposed Use Pattern for Spirodiclofen Crop Ty pe/Use Site Max Single

Application Rate (lb ai/A) Application

Equipment Application

Interval Maximum lb ai

per crop, season or year Max #

applications Pre
harvest Interval E NVIDOR® Miticide (EPA Reg # 264 - 831 ) 2 lb ai/gal liquid or 240 grams per liter Soluble Concentrate Liquid REI = 12 hours Tropical Fruit Subgroup 1 0.31 Airblast, aerial Not provided 0. 31 lb ai/acre 1 app per crop season 2 day 1 Crops include avocado, black sapote, cani stel, mamey sapote, mango, papaya, sapodilla, and star apple 

### 4.0 Occupational Exposure 4.1 Short and Intermediate Term Non - Cancer Exposures 4.1 .1 Occupational Handler Exposure and Risk EstimatesPage 7 of 17



### There is potential for occupati onal handler exposure from the proposed uses on agricultural crops. It is anticipated that the following scenarios could result in handler exposure: Mixer/L oaders: 1) Mixing/L oading L iquids for Airblast Applications (PHED); 2 ) Mixing/L oading L iquid s for Aerial Applications (PHED); Applicators: 3 ) Applying Spray s via Airblast Equipment (PHED); 4) Applying Spray s via Aerial Equipment (PHED) ; and Flagger: 5) Flagging to support aerial applications (PHED)
. No chemical
- specific data were available with which to assess potential exposure to pesticide handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data available in the Pesticide Handlers Exposure Database (PHED, August, 1998). For pesticide handlers , HED presents estimates of dermal exposure for “baseline” (i.e., workers wearing 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 protectiv e gloves or other personal protective equipment (PPE), as might be necessary. The spirodiclofen product label direct s mixers, loaders, applicators and other handlers to wear a long
- sleeve shirt, long pants, waterproof gloves and shoes plus socks. Handler exposure is expected to be short
- term based on information provided on the proposed label (e.g., onl y one application allowed per crop season) . The average adult body weight of 70 kg was used for estimating inhalation and dermal dose. Intermediate and l ong - term exposures are not expected, therefore, an intermediate and long
- term assessment was not conducted
. Daily dermal or inhalation handler exposures are estimated for each applicable handler task with the application rate, the area treated in a day , and the applicable dermal or inhalation unit exposure using the following formula: Daily Exposure (mg ai/day) = Unit Exposure (mg ai/lb ai handled) x Application Rate (lbs ai/area) x Daily Area Treated (area/day) 

### Where: Daily Exposure = Amount (mg a i/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 (mg ai/lb ai) derived from August 1998 PHED data; Application Rate = N ormalized application rate based on a logical unit treatment, such as acres; and Daily Area Treated = Normalized application area based on a logical unit treatment such asPage 8 of 17 acres (A/day). 

### The daily dermal or inhalation dose is calculated by normalizing the daily

exposure by

body weight and adjusting, if necessary , with an appropriate dermal or inhalation absorption factor using the following formula: 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 ai/kg body weight/day); Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption o r 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 (% of the total available absorbed); and Body Weight = Body w eight det ermined to represent the population of interest in a risk assessment (kg). 

### Non
- cancer dermal and inhalation risks for each applicable handler scenario are calculated using a MOE, which is a ratio of the NOAEL or LOAEL to the dail y dose. All MOE values we re calculated using the formula below:

MOE= NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day) 

### Total Average Daily Dose: When the dermal and inhalation endpoints, effects, and routes of exposure are the same, the doses may be added together to obtain a total dose using the following formula: TOTAL 

### Average Daily Dose = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day

### ) Table 4 presents the estimated risks for workers based on the short
- term dermal and inhalation exposures with baseline atti re , or with additional PPE
. HED has determined that risks are not of concern for short
- term exposures (i.e., MOEs > 3 00) with the PPE required on the label
. HED has no data to assess exposures to pilots using open cockpits. The only data available for e xposure to pilots is in enclosed cockpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long
- sleeve shirt, long pants, shoed and socks); pilots are not required to wear gloves. There were no risks of concern for aerial applicators.Page 9 of 17



### Table 4. Occupational Handler Dermal and Inhalation Exposures and Risk Estimates Dermal and Inhalation Unit Exposures (mg/lb ai) Application

rate (lb ai/A) a Area Treated

Daily (A) b Short
- term Doses (mg/kg/day) c Short
- term MOEs d
Mixer/Loader

– Airblast Application Dermal Baseline e : 2.9 Inhalation Baseline f: 0.0012 0. 3 1 40 Dermal Baseline: 0.01 Com

bined Baseline: 0.01 Dermal

Baseline: 820 Com

bined Baseline: 800 Inhalation Baseline: 0.00 02 Inhalati on Baseline: 40 ,000 Mixer/Loader

– Aerial Application Dermal Baseline: 2.9 Single layer w/gloves h : 0.023 Inhalation Baseline: 0.0012 0. 3 1 350 Dermal Baseline: 0.09 Single layer w/gloves : 0. 00071 Com

bined Baseline: 0.092
Com bined Single layer w/g loves: 0.00 27 Dermal

Baseline: 93 Single layer w/ gloves : 12,000 Com

bined Baseline: 92 Com bined Single layer w/gloves: 3,300 Inhalation Baseline: 0.00 2 Inhalation Baseline: 4,500 Applicator

–

Airblast Application Dermal Baseline: 0.36 Inhalatio n Baseline: 0.0045 0. 3 1 40 Dermal Baseline: 0.0 013 Com

bined Baseline: 0.0021 Dermal

Baseline: 6,600 Com

bined Baseline: 4,100 Inhalation Baseline: 0.000 8 Inhalation Baseline: 11,0 00 Applicator

–

Aerial Application Dermal Engin e ering Control g : 0.005 Inhalation Engin e ering Contro l g : 0.000068 0. 3 1 350 Dermal Engin e ering Contro l: 0.00016 Com

bined Engineering control: 0.00027 Dermal

E ngin e ering Contro l : 54,000 Com

bined Engineering control: 32,000 Inhalation Engin e ering Contro l: 0.00011 Inhalation E ngin e ering Contro l : 80,000 Flagger

– Aerial Application Dermal Baseline: 0.011 Inhalation Baseline: 0.00074 0.31 350 Dermal Baseline: 0.00 034 Com

bined Baseline: 0.0009 Dermal

Baseline: 25,000 Com

bined Baseline: 9,500 Inhalation Baseline: 0.000 5 4 Inhalation Baseline: 15,000 a Application rates are the maximum (single) recommended rates provided on the spirodiclofen product labels. b Ar ea treated per day values are HED estimates based on ExpoSAC Policy #9 “Standard Values for Daily Acres Treated in

Agriculture,” industry sources, and HED estimates. c Dose (mg/kg/day) = Unit exposure(mg/lb ai) x App Rate (lb ai/acre) x Area Treated (acres/day) x %Absorption (2 % dermal

and 100% inhalation assumed) / Body weight. The body weight is 70 kg for the in halation and dermal dose. d MOE = NOAEL or LOAEL /Dose; where the short
- term dermal and inhalation LO AE L = 8.4 mg/kg/day
.Page 10 of 17

e Baseline Dermal : Long - sleeve shirt, long pants, and no gloves. f Baseline I

nhalation: no respirator. g Eng Con Dermal and I nhalation Engineering control for the aerial application scenario is an enclosed cockpit and baseline attire (long
sleeve shirt, long pants, shoes, and socks)
. h PPE
- SL w/ gloves: Single layer plus chemical
- resistant gloves.

. 

### 4. 1. 2 Occupational Post - applic ation Exposure and Risk Estimates Since spirodiclofen is applied as a foliar spray
. HED expects that post
- application exposure will occur since spirodiclofen is applied as a foliar spray. Post
- application exposure is expected to be short
- term based on i nformation provided on the proposed label. P ost - application data has been submitted previously

for the use of spirodiclofen on citrus and apple. Post
- application exposures have been assessed usi ng the submitted dislodgeable foliar residue data as well as dermal transfer coefficients from HED’s ExpoSAC Policy Number 3.1 “Agricultural Transfer Coefficients” (August, 2000). Table 5 summarizes the scenarios assessed. In addition, the following assumptions were used in the calculations: Assumptions:

• Exposure Duration = 8 hours per day
• Body Weight = 70 kg
• Dermal Absorption = 2% Table 5: Anticipated Postapplication Activities and Dermal Transfer Coefficients Proposed Crops Policy Crop Group Category Application

Rate (lb ai/acre) Transfer

Coefficients (cm 2/hr) Activities Avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla, and star apple Tropical Fruit Subgroup 0.31 1500 Harvesting 3000 Thinning The information in the table is based on proprietary and non
- proprie tary data. 

### A DFR study

was submitted to the Agency by Bayer Corporation which examined the dissipation of residues on citrus and apple trees following application of spirodiclofen (ENVIDOR® 

### 2 SC Miticide). The study was reviewed by

HED and deemed accept able for use in occupational post
- application risk assessments (Memo, M. Dow, D285247, MRID 456973
- 13, June 29 , 2004 ). In the study , there were three test sites for citrus (California, Florida and Texas) and two apple test sites (Washington and Ontario, C anada). A single application was made at all test sites using ty

pical, orchard, airblast equipment. Maximum residues were identified at the Washington site for apples and those residue values were used in this risk assessment to estimate exposure from treatment of tropical fruit. Since the maximum application rate for apples in the study was 0. 11 lb ai/A, an adjustment of the residues was performed to account for the maximum application rate in this assessment (0.31 lb ai/A). A summary of the DFR data i s provided in Table 6
.Page 11 of 17



### Table 6: Summary of Apple DFR Data Used for Postapplication Assessment Trial Location Actual

Application Rate (lbs ai/A) Label

Recommended Maximum Application Rate (lbs ai/A) Day

after treatment DFR data provided in

study Adjusted DFR

data for differen ce in application rates a

Washington 0.11 0.31 0 0.169 0.476 1 0.165 0.465 2 0.161 0.454 3 0.157 0.443 4 0.154 0.433 5 0.150 0.423 6 0.146 0.413 7 0.143 0.403 8 0.140 0.394 9 0.136 0.384 10 0.13 3 0.375 11 0.130 0.366 12 0.127 0.358 13 0.124 0.349 14 0.121 0.341 15 0.118 0.333 16 0.115 0.325 17 0.113 0.318 18 0.110 0.310 19 0.107 0.303 20 0.105 0.296 21 0.102 0.289 22 0.100 0.282 23 0.098 0.275 24 0.095 0.269 25 0.093 0.263 26 0.091 0.256 27 0.089 0.250 28 0.087 0.245 29 0.085 0.239 30 0.083 0.233 a. DFR data in study collected after an application at a rate of 0. 11 lb ai/A. Maximum application rate assessed for spiro diclofen is 0.31

lb ai/A; therefore, the DFR data was adjusted to reflect this difference (0.31 lb ai/A / 0. 11 lb ai/A *DFR data) 

### Equations/Calculations: Daily dermal exposures were calculated on each postapplication day after application using the following equation: Daily Dermal Dose t = [DFR t (μg/cm

2 ) x 0.001 mg/μg x TC (cm 2/hr) x DA x ET (hrs)] / BW (kg) 

### Where, DFR t = dislodgeable foliage residue on day "t" (ug/cm2 ) ; TC = transfer coefficient (cm 2/hr) ; DA = dermal absorption factor ( 2 %) ; ET = exposure time (8 hr/day) ; and BW = body weight (70 kg)
.Page 12 of 17



### Once dail y exposures are calculated, the calculation of daily absorbed dose and the resulting Margin of Exposures use the same algorithms that are described above for the handler exposures. These calculations are completed for each day or appropriate block of time after application. HED has determined that short
- term risk estimates are not of concern (i.e., MOEs > 3 00) on the day of treatment (i.e., Day

0) for all po stapplication exposure activities. Table 7 presents a summary of occupational postapplication risks associated with use of spirodiclofen
. Table 7 . Post - application Risk Estimates for Spirodiclofen Crop Application

Rate (lb ai/A) Transfer Coefficient

(cm 2/hr) DFR

(ug/cm2 ) Day s After

Treatment Daily Dose 1

(mg/kg/ay) MOE 2 Tropical Fruit Subgroup 0. 3 1 1 , 500 0. 476 0 (12 hours) 0.0016 5 ,100 3 , 000 0.0 03 2 ,6 00 The information in the table is based on proprietary and non
-proprietary data. 1: Daily Dos e = [DFR (ug/cm2 ) x TC (cm2/hr) x 0.001 mg/μg x Dermal Absorption (2 % ) x 8 hrs/day] ÷ Body Weight (70 kg) 2: L OAEL/Daily Dose (Short
- term L OAEL = 8.4 mg/kg/day) 

### 4.2 Cancer Exposure Estimates This section presents the occupational handler exposure and cancer risk assessment from spirodiclofen
. 4.2.1 Occupational Handler Cancer Exposure and Risk Estimates Cancer risk estimates resulting from exposures to spirodiclofen were calculate d using a linear low
- dose extrapolation approach in which a Lifetime Average Dail y Dose (LADD) is first calculated and then compared with a Q 1 

### * that has been calculated for spirodiclofen based on dose response data (Q 1 

### * = 1
. 49 x 10 - 2 

### (mg/kg/day) - 1 

### ). Abs orbed average daily dose (ADD) levels were used as the basis for calculating the LADD values. These values also serve as the basis for the cancer risk estimates. Dermal and inhalation ADD values were first added together to obtain combined ADD values. LADD values were then calculated and multiplied by the Q 1 

### * to obtain cancer risk estimates. To estimate the carcinogenic risk from absorbed average daily dose, the values must be amortized over the working lifetime of occupational handlers. Based on use s cenario and use patterns, it is anticipated that commercial applicators would apply spirodiclofen approximately 30 day s per year. It was estimated that an individual farmer would handle spirodiclofen approximately

10 day s per year. As a result, HED consi dered two handler populations ( commercial and private handlers ) for the cancer risk assessment. Finall y, a 35 year career and a 70 year lifespan were used to complete the calculations. Generall y, HED considers occupational cancer risks estimates in the 1 0 - 6 

### 10 - 4 

### range to be not of concern. LADD values were calculated using the following equation: LADD = ADD * (Exposure Frequency / 365 days per year) * (Exposure duration * Lifetime)Page 13 of 17

Where: Lifetime Average Daily Dose = the amount as absorbed dose rec eived from exposure to a pesticide or degradate in a given scenario over a lifetime (mg/kg/day, also referred to as LADD); Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide or degradate in a given scenario on a dai ly basis (mg/kg/day, also referred to as ADD); Exposure Frequency = the annual frequency of exposure to an individual (days/year); Exposure Duration = the amount of a lifetime that an individual is exposed ( 35 years for occupational); and Lifetime = the average life expectancy of an individual (70 years). 

### Estimated cancer risk calculations were completed by multiplying the LADD values b y the Q 1 

### * for spirodiclofen (Q 1 

### * = 1
. 49 x 10 - 2 

### (mg/kg/day) - 1 

### ). Cancer risk estimates were calculated using th e following equation: Estimated Cancer Risk = LADD x Q1* Where: Estimated Cancer Risk = Probability of excess cancer cases over a lifetime (unitless); Lifetime Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide or degradate in a given scenario over a lifetime (mg//kg/day); and Q1* = Quantitative dose response factor used for linear, low
- dose response cancer risk calculations (mg/kg/day) - 1

. 

### Estimated spirodiclofen cancer risks for handlers are summarized below in Table s 8 and 9 . In most scenarios, estimated cancer risks are below 1 x 10 - 6 

### at some level of risk mitigation. C ancer risk estimates are below 1 x 10 - 4 

### with the single layer clothing, gloves, and no respiratory protection. Therefore, there are no concern s for occupational cancer risk for handlers.

Table 8 . Handler Cancer Risk Estimates for Commercial Spirodiclofen Handlers Scenario Mitigation Dermal Dose a (mg/kg/day) Inhalation

Dose a (mg/kg/day) Com

bined ADD b (mg/kg/day) Commercial

LADD c (mg/kg/day) Commercial

Cancer Risk d Mixer/Loader
Mixing/loading liquids airblast application (1) Baseline Dermal and

Inhalation 0.01 0.0002 0.01 4.3E
- 04 6.4E
- 06
Single layer w/gloves + Baseline Inhalation 0.000081 0.000 29 1.2E
- 05 1.8E
- 07 Mixing/loading liquids for aerial application (2) Baseline Dermal and

Inhalation 0.0 9 0.00 2 0.092 3.8E
- 03 5.6E
- 05Page 14 of 17



### Table 8 . Handler Cancer Risk Estimates for Commercial Spirodiclofen Handlers Scenario Mitigation Dermal Dose a (mg/kg/day) Inhalation

Dose a (mg/kg/day) Com

bined ADD b (mg/kg/day) Commercial

LADD c (mg/kg/day) Commercial

Cancer Risk d Single layer w/gloves + Baseline Inhalation 0.00071 0.0027 0.00011 1.6E
- 06 Applicator Applying spray using airblast (3) Baseline Dermal and Inhalation 0.0013 0.0008 0.0021 8.5E
- 05 1.3E
- 06
Applying spray using aerial (4) Engineering Controls

Dermal and Inhalation 0.00016 0.00011 0.00027 1.1E
- 05 1.6E
- 07 Flagger Flagging during aerial application (5) Basel ine Dermal and

Inhalation 0.00034 0.0005 0.0009 3.6E
- 05 5.4E
- 07 a. Dermal Dose and Inhalation Doses (mg/kg/day) = See Table 4. b. Combined ADD (mg/kg/day) = Dermal Dose (mg/kg/day) + Inhalation Dose ( mg/kg/day) c. Commerc ial Applicator LADD (mg/kg/d ay) = ADD x [(30 days/yr)/ (365 days/yr)] x (35 yrs/70yrs) d Commercial Applicator Cancer Risk = Commercial LADD x Q* [ 1.49 x 10 - 2 (mg/kg/day) - 1 ]


### Table 9 . Handler Cancer Risk Estimate s for Private Spirodiclofen Handlers S cenario Mitigation Dermal Dose a (mg/kg/day) Inhalation

Dose a (mg/kg/day) Com

bined ADD b (mg/kg/day) Private

LADD c (mg/kg/day) Private

Cancer Risk d Mixer/Loader Mixing/loading liquids airblast application (1) Baseline Dermal and

Inhalation 0.01 0.00 02 0.01 1.4E
- 04 2.1E
- 06

Mixing/loading liquids for aerial application (2) Baseline Dermal and

Inhalation 0.0 9 0.0002 0.092 1.3E
- 03 1.9E
- 05 Single layer w/ gloves + Baseline Inhalation 0.00071 0.0027 3.5E
- 05 5.3E
- 07 Applicator Applying spray using airblast (3) Baseline Dermal and Inhalation 0.001 3 0.000 8 0.0021 2.8E
- 05 4.2E
- 07
Applying spray using aerial (4) Engineering Controls

Dermal and Inhalation 0.0001 6 0.0001 1 0.0002 7 3.6E
- 06 5.3E
- 08Page 15 of 17



### Table 9 . Handler Cancer Risk Estimate s for Private Spirodiclofen Handlers S cenario Mitigation Dermal Dose a (mg/kg/day) Inhalation

Dose a (mg/kg/day) Com

bined ADD b (mg/kg/day) Private

LADD c (mg/kg/day) Private

Cancer Risk d Flagger Flagging during aerial application (5) B aseline Dermal and

Inhalation 0.00034 0.0005 0.000 9 1.2E
- 05 1.8E
- 07 a. Dermal and Inhalation Dose (mg/kg/day) = See Table 4. b. Combined ADD (mg/kg/day) = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day) c. Private Applicator LADD (mg/kg/day) = ADD x [( 1 0 days/yr)/ (365 days/yr)] x (35 yrs/70yrs) d Private l Applicator Cancer Risk = Private LADD x Q* [ 1.49 x 10 - 2 (mg/kg/day) - 1 ] 

### 4.2.2 Occupational Post - application Cancer Exposure and Risk Estimates The occupational exposure and cancer risk calculations for post
- application workers are presented in this section. The use of dissipation data and the manner in which daily post application dermal exposures w ere calculated are inherentl y different than with handler exposures. However, once dail y exposures are calculated, the calculation of LADD (Lifetime Average Dail y Dose) and the resulting cancer risk estimates use the same algorithms that are described abo ve for the handler exposures. Post
- application c ancer risk estimates are summarized in Table 10 below
. Exposure was assessed for individuals employed b y multiple establishments (i.e., commercial or migratory farmworkers) who could be exposed up to 30 day s per year. Dislodgeable foliar residue data for spirodiclofen were used along with transfer coefficients to calculate the LADDs. An average DFR value w as calculated using spirodiclofen
- specific dissipation data
. Based on a review of the proposed labe l, it was determined that: (1) onl y one application is allowed per crop season , (2) residues are assumed to dissipate over time, and (3) it is unlikely that workers will be exposed to Day

0 residues 30 day s a year. Therefore, HED used the average residue over 30 day s to estimate cancer risk. Lifetime Average Daily Dose = 

### ADD x Exposure Frequency x Exposure Duration 365 Days per Year 

### Lifetime where Lifetime Average Daily Dose = The amount as absorbed dose received from exp osure to a pesticide or degradate in a given scenario over a lifetime (mg/kg/day, also referred to as LADD); Average Daily Dose = The amount as absorbed dose received from exposure to a pesticide or degradate in a given scenario on a daily basis (mg/kg/ day , also referred to as ADD); Exposure Frequency = The annual frequency of exposure to an individual (30 days/year); Exposure Duration = The amount of a lifetime that an individual is exposed (35 years for occupational); and Lifetime = The avera ge life expectancy of an individual (70 years). 

### Estimated Cancer Risk = LADD x Q1*Page 16 of 17

Where: Estimated Cancer Risk = Probability of excess cancer cases over a lifetime (unitless); Lifetime Average Daily Dose = The amount as absorbed dose received from e xposure to a pesticide or degradate in a given scenario over a lifetime (mg/kg/day); and Q 1 * = Quantitative dose response factor used for linear, low
- dose response cancer risk calculations [3.59 x 10 - 3 

### ( mg/kg/day) - 1 ]. 

### Estimated spirodiclofen cancer risks for post
- application exposure are summarized in Table 10. The estimated cancer risks are below or equal to 1 x 10 - 6 

### . Therefore, there are no concerns for occupational cancer risk for post
- application workers. Table 10 . Cancer Exposure/Risk Estim ates for Spirodiclofen Post - application Workers Crop DAT a DFR b

(ug/cm2 ) Transfer

Coefficient c (cm 2/hr) Daily Dose d

(mg/kg/day) LADD e Cancer Risk f
Tropical Fruit Subgroup 1
- 30 0. 34 1 , 500 0.0012 0.000048 7.14E
- 07
3 , 000 0.0023 0.000096 1. 43E
- 06

a. DAT= 30 day residue average b. DFR value used is based on a DFR study submitted to the Agency by Bayer Corporation 

### in 2004 c. Transfer Coefficients selected in accordance with SAC for Exposure Policy 3.1 (August 2000) d. Daily Dose (mg/kg/day)= DFR (μg/ cm2 ) x 0.001 mg/ug x Tc (cm2/hr) x DA ( 2 %) x ET (8 hr/day)/70 kg e. LADD (mg/kg/day) = DD x [(30 days/yr)/ (365 days/yr)] x (35 yrs/70yrs) f. Cancer Risk = LADD x Q* [ 1.49 x 10 - 3 (mg/kg/day) - 1 ] 

### 5.0 Non - Occupational/Residential Exposure Estimates This docum ent only

presents the assessment of proposed agricultural uses of spirodiclofen
. No residential uses are being requested at this time and, in addition, there are no existing spirodiclofen products registered for residential use sites; therefore, no residential risk assessment has been conducted. 6.0 Non - Occupational Off - Target Exposure Estimates Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial application, but, to a l esser extent, could also be a potential source of exposure from the ground application method additionally employed for spirodiclofen . The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and 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, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied b y air, orchard airblastPage 17 of 17



### and ground h ydraulic 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 aerial as well as other application types where a ppropriate.