 

	

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)  SEQ CHAPTER
\h \r 1 		

THROUGH:	Kelly M. Lowe, Environmental Scientist

Dana Vogel, Branch Chief

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

TO:		Rita Kumar, PM (11)		  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 

		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.

TABLE OF CONTENTS

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc240349222"  1.0	Executive
Summary	  PAGEREF _Toc240349222 \h  3  

  HYPERLINK \l "_Toc240349223"  2.0	Hazard Profile	  PAGEREF
_Toc240349223 \h  4  

  HYPERLINK \l "_Toc240349224"  3.0	Use Profile	  PAGEREF _Toc240349224
\h  6  

  HYPERLINK \l "_Toc240349225"  4.0	Occupational Exposure	  PAGEREF
_Toc240349225 \h  6  

  HYPERLINK \l "_Toc240349226"  4.1	Short and Intermediate Term
Non-Cancer Exposures	  PAGEREF _Toc240349226 \h  6  

  HYPERLINK \l "_Toc240349227"  4.1.1	Occupational Handler Exposure and
Risk	  PAGEREF _Toc240349227 \h  6  

  HYPERLINK \l "_Toc240349228"  4.1.2	Occupational Postapplication
Exposure and Risk	  PAGEREF _Toc240349228 \h  10  

  HYPERLINK \l "_Toc240349229"  4.2	Cancer Exposures	  PAGEREF
_Toc240349229 \h  12  

  HYPERLINK \l "_Toc240349230"  4.2.1	Occupational Handler Cancer
Exposure and Risk	  PAGEREF _Toc240349230 \h  12  

  HYPERLINK \l "_Toc240349231"  4.2.2	Occupational Postapplication
Cancer Exposure and Risk	  PAGEREF _Toc240349231 \h  15  

  HYPERLINK \l "_Toc240349232"  5.0 Non-Occupational/Residential
Exposure	  PAGEREF _Toc240349232 \h  16  

  HYPERLINK \l "_Toc240349233"  6.0	Non-Occupational Off-Target Exposure
  PAGEREF _Toc240349233 \h  16  

 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 dermal-absorption 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 10-2 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 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 1/28/99). 

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 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 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 10-2 in
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	

–



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 	Pre-harvest 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

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

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 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.

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 Controlg:

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: 9,500



	Inhalation 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.  

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
(long-sleeve 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.

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).

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  tc \l3 "2.1.4 	Cancer Permethrin Handler
Exposure and Risk Assessment 

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 -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)

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:

 EQ 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 10-6 at 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.

  SEQ CHAPTER \h \r 1 

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

	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]   

  SEQ CHAPTER \h \r 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



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
tc \l3 "2.2.4	Occupational Postapplication Exposure and Risk Estimates
for Cancer 

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 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*

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

DAT= 30 day residue average

DFR value used is based on a  DFR study  submitted to the Agency by
Bayer Corporation in 2004  

Transfer Coefficients selected in accordance with SAC for Exposure
Policy 3.1 (August 2000)

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

LADD (mg/kg/day) = DD x [(30 days/yr)/ (365 days/yr)] x (35 yrs/70yrs) 

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. 

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 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.

Page   PAGE  3  of   NUMPAGES  17 

