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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF 

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM 

DATE: 9/23/09

SUBJECT: Spirodiclofen: Occupational and Residential Exposure/Risk Assessment for the 

Tropical Fruit Subgroup

 

PC Code: 124871 DP Barcode: D363346

Decision No.: 404221 Registration No.: 264-831

Petition No.: 8F7500 Regulatory Action: Section 3 Registrations

Risk Assessment Type: ORE Case No.: NA

TXR 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)

Registration Division

Introduction 

The registrant, Bayer 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). Bayer CropScience have requested these crops be added to the 

end use product, ENVIDOR®2 SC Miticide (EPA Reg. No 264-831). No 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.
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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............................................................................. 16
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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: 

ENVIDOR® 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 intermediate- 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 dermalabsorption study. In the absence of an available 21/28 day inhalation 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 Q1

*

(mg/kg/day)

-1

of 1.49 x 10-2in 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 primarily acaricides with insecticidal uses at higher doses. The mode of action occurs 

through the inhibition of lipid biosynthesis, which inhibits the ability to develop through the 

various mite growth stages and the ability to reproduce in adults. Spirodiclofen is structurally 

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 

proposed by 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 chemical-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 assess 

handler exposures for regulatory actions when chemical-specific monitoring data are not 

available (HED Science Advisory Council for Exposure (ExpoSAC) Draft SOP # 7, dated 
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1/28/99). 

Handler and post-application exposure is expected to be short-term based on information 

provided on proposed labels (e.g., only one application allowed per crop season). Airblast and 

aerial applications were assessed. All short-term risks for occupational handlers do not exceed 

HED's level of concern (i.e., MOEs ≥ 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 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. 

Under the conditions described herein (i.e., regarding hazard identification and application 

practices), the interim worker protection standard (WPS) REI of 12 hours is adequate to protect 

agricultural worker from post-application exposures. 

Residential Exposure/Risk

Spirodiclofen is not proposed or registered 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 for Use on Hops.” The

acute toxicity categories for spirodiclofen 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) is the 

Lowest Observable Adverse Effect Level (LOAEL), 8.4 mg/kg/day. The toxic effects noted 

were increased adrenal gland weight which corroborated with histopathology findings

(cytoplasmic 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 LOAEL versus 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 oral 
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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 

Quantitative Risk Assessment (Q1

*

) 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 “Likely 

to be Carcinogenic to Humans” and assigned a Q1

*

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 Q1

*

(mg/kg/day)

-1

of 1.49 x 10-2in human equivalents based 

on male rat testes Leydig cell adenoma.

Spirodiclofen is 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 Spirodiclofen

OPPTS Guideline Study Type Results Toxicity 

Category

870.1100 Acute oral toxicity / rat LD50 => 2000 mg/kg (males and females) III

870.1200 Acute dermal toxicity / rat LD50 => 2000 mg/kg (males and females) III

870.1300 Acute inhalation toxicity / 

rat LC50 => 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 –
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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-term 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 Q1* (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 20 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 

Type/Use 

Site

Max Single 

Application 

Rate (lb ai/A)

Application 

Equipment

Application 

Interval

Maximum lb ai 

per crop, season 

or year

Max # 

applications 

Preharvest 

Interval 

ENVIDOR® Miticide (EPA Reg #264-831)

2 lb ai/gal liquid or 240 grams per liter

Soluble Concentrate Liquid

REI = 12 hours

Tropical 

Fruit 

Subgroup1

0.31 Airblast, aerial Not provided 0.31 lb ai/acre 1 app per 

crop season

2 day

1 Crops include avocado, black sapote, canistel, 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 Estimates
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There is potential for occupational handler exposure from the proposed uses on agricultural 

crops. It is anticipated that the following scenarios could result in handler exposure:

Mixer/Loaders:

1) Mixing/Loading Liquids for Airblast Applications (PHED);

2) Mixing/Loading Liquids for Aerial Applications (PHED);

Applicators:

3) Applying Sprays via Airblast Equipment (PHED);

4) Applying Sprays 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 protective gloves or other personal 

protective equipment (PPE), as might be necessary. The spirodiclofen product label directs

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., only one application allowed per crop season). The average adult body weight of 70 

kg was used for estimating inhalation and dermal dose. Intermediate and long-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 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 (mg ai/lb ai) derived from August 1998 PHED 

data;

Application Rate = Normalized 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 as 
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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 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 (% of the total available 

absorbed); and

Body Weight = Body weight determined 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 daily dose. All MOE values were 

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 attire, or with additional PPE. HED has determined that risks are not of 

concern for short-term exposures (i.e., MOEs > 300) with the PPE required on the label.

HED has no data to assess exposures to pilots using open cockpits. The only data available for 

exposure 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.
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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 MOEsd

Mixer/Loader – Airblast Application

Dermal

Baselinee: 2.9

Inhalation

Baselinef: 0.0012

0.31 40

Dermal

Baseline: 0.01 Combined

Baseline: 

0.01

Dermal

Baseline: 

820 Combined

Baseline: 

800 Inhalation

Baseline: 

0.0002

Inhalation

Baseline: 

40,000

Mixer/Loader – Aerial Application

Dermal

Baseline: 2.9

Single layer 

w/glovesh: 0.023

Inhalation

Baseline: 0.0012

0.31 350

Dermal

Baseline: 0.09

Single layer 

w/gloves: 

0.00071

Combined

Baseline: 

0.092

Combined

Single layer 

w/gloves: 

0.0027

Dermal

Baseline: 

93

Single layer 

w/ gloves: 

12,000

Combined 

Baseline: 

92

Combined

Single layer 

w/gloves: 

3,300

Inhalation

Baseline: 

0.002

Inhalation

Baseline: 

4,500

Applicator –Airblast Application

Dermal

Baseline: 0.36

Inhalation

Baseline: 0.0045

0.31 40

Dermal

Baseline: 

0.0013 Combined

Baseline: 

0.0021

Dermal

Baseline: 

6,600 Combined

Baseline: 

4,100 Inhalation

Baseline: 

0.0008

Inhalation

Baseline: 

11,000

Applicator –Aerial Application

Dermal

Engineering Controlg:

0.005

Inhalation

Engineering Control

g

:

0.000068

0.31 350

Dermal

Engineering 

Control: 

0.00016

Combined 

Engineering 

control: 

0.00027

Dermal

Engineering 

Control:

54,000

Combined

Engineering 

control: 

32,000

Inhalation

Engineering 

Control: 

0.00011

Inhalation

Engineering 

Control: 

80,000

Flagger –Aerial Application

Dermal

Baseline: 0.011

Inhalation

Baseline: 0.00074

0.31 350

Dermal

Baseline: 

0.00034

Combined

Baseline: 

0.0009

Dermal

Baseline: 

25,000 Combined

Baseline: 

Inhalation 9,500

Baseline: 

0.00054

Inhalation

Baseline: 

15,000

a Application rates are the maximum (single) recommended rates provided on the spirodiclofen product labels.

b Area 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 inhalation and dermal dose. 

d MOE = NOAEL or LOAEL/Dose; where the short-term dermal and inhalation LOAEL = 8.4 mg/kg/day. 
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e Baseline Dermal: Long-sleeve shirt, long pants, and no gloves.

f Baseline Inhalation: no respirator.

g Eng Con Dermal and Inhalation Engineering control for the aerial application scenario is an enclosed cockpit and baseline attire (longsleeve shirt, long pants, shoes, and socks).

h PPE - SL w/ gloves: Single layer plus chemical-resistant gloves.

.

4.1.2 Occupational Post-application 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 information provided on the proposed label. Post-application data has been 

submitted previously for the use of spirodiclofen on citrus and apple. Post-application exposures 

have been assessed using 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 

(cm2/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-proprietary 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 acceptable 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, Canada). A single application was made at all 

test sites using typical, 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 is provided in

Table 6.
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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 

difference in 

application 

ratesa

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 0.133 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 spirodiclofen 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 Doset = [DFRt (μg/cm2) x 0.001 mg/μg x TC (cm2/hr) x DA x ET (hrs)] / BW (kg)

Where,

DFRt = dislodgeable foliage residue on day "t" (ug/cm2);

TC = transfer coefficient (cm2/hr);

DA = dermal absorption factor (2%) ;

 ET = exposure time (8 hr/day); and

BW = body weight (70 kg).
Page 12 of 17

Once daily 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 > 300) on the 

day of treatment (i.e., Day 0) for all postapplication 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

(cm2/hr)

DFR 

(ug/cm2)

Days After 

Treatment

Daily Dose1

(mg/kg/ay) MOE2

Tropical Fruit 

Subgroup 0.31

1,500

0.476 0

(12 hours)

0.0016 5,100

3,000 0.003 2,600

The information in the table is based on proprietary and non-proprietary data.

1: Daily Dose = [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: LOAEL/Daily Dose (Short-term LOAEL = 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 calculated using a linear 

low-dose extrapolation approach in which a Lifetime Average Daily Dose (LADD) is first 

calculated and then compared with a Q1* that has been calculated for spirodiclofen based on 

dose response data (Q1* = 1.49 x 10-2(mg/kg/day)-1). Absorbed 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 Q1* 

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 scenario and use 

patterns, it is anticipated that commercial applicators would apply spirodiclofen approximately

30 days per year. It was estimated that an individual farmer would handle spirodiclofen

approximately 10 days per year. As a result, HED considered two handler populations 

(commercial and private handlers) for the cancer risk assessment. Finally, a 35 year career and a 

70 year lifespan were used to complete the calculations. Generally, HED considers occupational 

cancer risks estimates in the 10 -610 -4range 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 received 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 daily 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 by the Q1* 

for spirodiclofen (Q1* = 1.49 x 10-2(mg/kg/day)-1). Cancer risk estimates were calculated using 

the 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 Tables 8 and 9. In 

most scenarios, estimated cancer risks are below 1 x 10-6at some level of risk mitigation. 

Cancer risk estimates are below 1 x 10-4 with the single layer clothing, gloves, and no respiratory 

protection. Therefore, there are no concerns 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)

Combined 

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 0.00029 1.2E-05 1.8E-07

Mixing/loading 

liquids for aerial 

application (2)

Baseline Dermal and 

Inhalation 0.09 0.002 0.092 3.8E-03 5.6E-05
Page 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)

Combined 

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)

Baseline 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. Commercial Applicator LADD (mg/kg/day) = 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 Estimates for Private Spirodiclofen Handlers

Scenario Mitigation

Dermal 

Dose a

(mg/kg/day)

Inhalation 

Dose a

(mg/kg/day)

Combined 

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 0.0002 0.01 1.4E-04 2.1E-06

Mixing/loading 

liquids for aerial 

application (2)

Baseline Dermal and 

Inhalation 0.09

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 0.0013 0.0008 0.0021 2.8E-05 4.2E-07

Applying spray 

using aerial (4)

Engineering Controls

Dermal and Inhalation 0.00016 0.00011 0.00027 3.6E-06 5.3E-08
Page 15 of 17

Table 9. Handler Cancer Risk Estimates for Private Spirodiclofen Handlers

Scenario Mitigation

Dermal 

Dose a

(mg/kg/day)

Inhalation 

Dose a

(mg/kg/day)

Combined 

ADD b

(mg/kg/day)

Private

LADD c

(mg/kg/day)

Private

Cancer

Risk d

Flagger

Flagging

during aerial 

application (5)

Baseline Dermal and 

Inhalation 0.00034 0.0005 0.0009 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 [(10 days/yr)/ (365 days/yr)] x (35 yrs/70yrs)

d Privatel 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 postapplication dermal exposures were calculated are inherently different than with handler 

exposures. However, once daily exposures are calculated, the calculation of LADD (Lifetime 

Average Daily Dose) and the resulting cancer risk estimates use the same algorithms that are 

described above for the handler exposures. 

Post-application cancer risk estimates are summarized in Table 10 below. Exposure was 

assessed for individuals employed by multiple establishments (i.e., commercial or migratory

farmworkers) who could be exposed up to 30 days per year. Dislodgeable foliar residue data for 

spirodiclofen were used along with transfer coefficients to calculate the LADDs. An average 

DFR value was calculated using spirodiclofen-specific dissipation data. Based on a review of 

the proposed label, it was determined that: (1) only 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 days a year. Therefore, HED used the average residue over 30 

days 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 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 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 average 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 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 [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 Estimates for Spirodiclofen Post-application Workers

Crop DAT a DFR b

(ug/cm2)

Transfer 

Coefficient c 

(cm2/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 document 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 always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser 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 appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast 
Page 17 of 17

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 aerial as well as other application types where appropriate.