Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

28-0CT-20 15 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Spirotetramat. Occupational and Residential Exposure Assessment for a 

Proposed Use on Citrus Trees Grown in Residential Areas 

PC Code: 39220 I 

Decision No.: 495325 

Petition No.: NA 

OP Barcode: 0429878 

Registration No.: 432-xxx 

Regulatory Action: Section 3 

Risk Assessment Type: Occupational/Residential Exposure Assessment Case No.: 7452 

TXR No.: NA CAS No.: 2033 13-25- 1 

MRID No.: NA 40 CFR: § 180.641 

From: 

Through: 

To: 

Introduction 

Health 

K

Risk 

elly 

Assessment 

M. 

Effec

Lowe, 

ts Division 

Environmental 

Branch 

(H

l 

ED, 

(RAB 

7509P) 

Scientist 

I) 

~ 

Charles Smith, Branch Chief 

RAB l/HED (7509P) 

and 

(_-.-~ 

~ 

Shalu Shelat, ExpoSAC Reviewer ~ < 

Barry O'Keefe, ExpoSAC Reviewer /] ~ I~ Exposure Science Advisory Committee (ExpoSAC) I HE~ 

Rita Kumar 

Fungicide Branch 

Registration Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an 

exposure and risk assessment for the proposed use of spirotetramat on citrus trees in residential 

areas. When registered, this will be the first residential use of spirotetramat. No risk estimates 

of concern were identified; all short- and intermediate-term occupational handler (with baseline 

attire) and short-term residential handler MO Es were greater than the level of concern (LOC = 

100). 

Page I of 13 
It is HED policy to use the best available data to assess exposure. Several sources of generic 

data were used in this assessment as surrogate data in the absence of chemical-specific data, 

including the Pesticide Handlers Exposure Database Version 1.1 (Pl-IED 1.1 ); the Agricultural 

Handler Exposure Task Force (AHETF) database; and the Outdoor Residentia l Exposure Task 

Force (ORETF) database. Some of these data are proprietary, and subject to the data protection 

provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on 719115. 

Page 2of 13 
Table of Contents 

1.0 Executive Summary .................................................................................................................. 4 

2.0 Risk Assessment Conclusions and Recommendations ............................................................. 5 

2.1 Summary of Risk Estimates .................................................................................................. 5 

2.2 Data Deficiencies and Requirements ............. ....................................................................... 5 

3.0 1-Iazard Characterization ............................................................................................................ 5 

4.0 Proposed Use Profile ........................................................... ...................................................... 7 

5.0 Residential Exposure and Risk Estimates ................................................................................. 7 

5.1 Residential Handler Exposure/Risk Estimates ...................................................................... 7 

5.2 Residential Post-application Exposure/Risk Estimates ........................................................ 8 

5.3 Residential Risk Estimates for Use in Aggregate Assessment ............................................. 9 

6.0 Occupational Exposure and Risk Estimates ............................................................................. 9 

6.1 Occupational Handler Exposure/Risk Estimates .................................................................. 9 

6.2 Occupational Post-application Exposure/Risk Estimates ................................................... 11 

Page 3 of 13 
1.0 Executive Summary 

Spirotetramat is a systemic insecticide, active against sucking insects. It can control hidden pests 

and protect new shoots. Spirotetramat is currently registered for use on a variety of agricultural 

crops, and is being proposed for use on citrus trees in residential areas. When registered, this 

will be the first residentia l use for spirotetramat. The proposed end-use product is a soluble 

concentrate (SC), 14ACP703 SC Insecticide/Miticide (EPA Reg. #432-xxxx), which contains 2 

lb ai/gallon or 22.4% ai. The proposed label allows for up to 2 foliar spray applications per year 

(with a 2 1 day retreatment interval) using handheld sprayers at a maximum single application 

rate of lO fl ozJA (0.156 lb ai/A), 4.25 fl ozJlOO gal (0.066 lb ai/100 gal) or 0.23 fl ozJlOOO ft2 

(0.0036 lb ai/ l 000 ft2). It is anticipated that there will be short- and intermediate-term 

occupational handler exposure, as well as short-term residential handler and post-application 

exposures from the proposed ornamental use. 

For spirotetramat, a dermal endpoint was not selected. Dermal endpoints were chosen in 

previous risk assessments; however, reevaluation of the toxicological database yielded no dermal 

hazard. Since there is no concern for enhanced sensitivity/susceptibility to offspring from 

spirotetramat exposure, the effects of concern in adults and offspring are adequately assessed in 

the dermal toxicity study where no adverse dermal or systemic effects were observed up to the 

limit dose. The inhalation point of departure (POD) is based on a 90-day oral toxicity study in 

dogs with a no observed adverse effect level (NOAEL) of 32 mg/kg/day. The LOC for 

inhalation exposure scenarios is for MO Es < I 00 ( 1 OX for interspecies extrapolation and 1 OX for 

intra.species variation). Since the NOAEL for inhalation risk assessment was chosen from an 

oral study, it was assumed that toxicity via the inhalation route is equivalent to oral toxicity. 

The residential handler exposure and risk estimates indicate that the short-term inhalation MOEs 

are not of concern to HED (i.e., MO Es :::: I 00). While residential post-application exposure may 

potentially occur for adults entering treated areas, there is no dermal POD for spirotetramat, 

therefore, a quantitative assessment was not conducted. 

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm inhalation MOEs are not of concern to HED (i.e., MOEs :::: 100) with baseline attire (e.g., 

long-sleeved shirt, long pants, shoes plus socks, no gloves or respirator). Since the product is 

proposed for use in residential settings only, it is not anticipated that commercial applicators 

would not return to the treated area after application. Therefore, a quantitative occupational 

post-application assessment was not conducted. 

Human Studies Review 

This risk assessment re lies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

PH ED 1.1; the AHETF database; and the ORETF database are (1) subject to ethjcs review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Page 4of13 
Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website 1

• 

2.0 Risk Assessment Conclusions and Recommendations 

2.1 Summary of Risk Estimates 

There are no residential or occupational risk estimates of concern for the proposed use of 

spirotetramat on residential citrus trees. All residential MOEs are greater than 5,500,000 and all 

occupational MOEs are greater than 690,000. 

2.2 Data Deficiencies and Requirements 

In accordance with the updated Part 158 data requirements (2007), a turf transferable residue 

(TTR) study is required for all occupational or residential turf uses, and one or more dislodgeable 

foliar residue (DFR) studies are required when a pesticide has residential or occupational uses 

that could result in post-application dermal exposure. Spirotetramat has no registered or 

proposed turf uses; therefore, a TTR study is not required at this time. A DFR study has been 

submitted for spirotetramat (MRID 46904605) and has been reviewed by the Agency (D407669); 

however, since there is no dermal point of departure, the study has not been used in this 

assessment. 

3.0 Hazard Characterization 

Acute Toxicity 

Spirotetramat is classified as Toxicity Category Ill for acute oral and acute dermal toxicity, 

Toxicity Category IV for acute inhalation toxicity, and Toxicity Category II for primary eye 

irritation. Spirotetramat is not an irritant to the skin of rabbits (Toxicity Category IV), but was 

shown to be a skin sensitizer in mice. Table 3. 1 presents a summary of the acute toxicity 

information for spirotetramat. 

Ta ble 3.1. Acute Tox icitv Profile - Soirotetrama t 

Guideline No. Study Type MRID(s) 

870.1100 Acute oral (rat) 46904527 

870.1200 Acute dermal (rat) 46904529 

870.1300 Acute inhalation (rat) 46904530 

870.2400 Primary eye irritation (rabbit) 46904531 

870.2500 Primary dermal irritation (rabbit) 46904532 

870.2600 Dermal sensitization (mouse) 46904565 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

hnp://www.epa.gov/pesticides/science/post-app-exposure-data.html 

Page 5of 13 

Results Toxicity 

Category 

LDso >2000 mg/kg (F) 111 

LDso >2000 mg/kg (M&F) III 

LCso >4.183 mg/L (M&F) IV 

Corneal opacity and iritis II (grade I); cleared by day 8 

Negative IV 

Positive NIA (Local Lymph Node Assay) 
Toxicological PO Os Used for Risk Assessment 

For spirotetramat, a dennal endpoint was not selected. Denna! endpoints were chosen in 

previous risk assessments; however, reevaluation of the toxicological database yielded no dennal 

hazard. Since there is no concern for enhanced sensitivity/susceptibility to offspring from 

spirotetramat exposure, the effects of concern in adults and offspring are adequately assessed in 

the dermal toxicity study where no adverse dermal or systemic effects were observed up to the 

limit dose. The inhalation POD is based on a 90-day oral toxicity study in dogs with a NOAEL 

of 32 mg/kg/day. The lowest-observed adverse-effect level (LOAEL) of72 mg/kg/day is based 

on depressed red blood cell parameters, thymus atrophy, and decreased food consumption. The 

LOC for inhalation exposure scenarios is for MO Es <100 (I OX for interspecies extrapolation and 

l OX for intraspecies variation). Since the NOA EL for inhalation risk assessment was chosen 

from an oral study, it was assumed that toxicity via the inhalation route is equivalent to oral 

toxicity. 

As part of the revised 40 CFR Toxicology Data Requirements, subchronic inhalation and 

subchronic neurotoxicity (SCN) studies are necessary for registered uses; however, the Hazard 

and Science Policy Council (HASPOC) concluded, using a weight-of-evidence approach, that 

these studies are not required at this time (TXR# 0056480). Although the SCN study is not 

required according to HASPOC, a SCN study has been submitted, and the results of the study 

incorporated into the current assessment (neurotoxic effects were not displayed up to the highest 

dose tested). 

A summary of the toxicological PODs and endpoints chosen for the relevant exposure scenarios 

for human risk assessment are found in Table 3.2. 

Table 3.2. Summa ry of Toxicological Doses and Endpoints for Spirotetramat for Use in Human Health Risk 

Assessments. 

Exposure Scenario POD Uncenainty LOC for Risk Study and Toxicological Effects Factors Assessment 

Dermal 

Shon- and In a dermal toxicity study in rats. no adverse effects were observed up to the limit dose. Since there is IntermediateTerm ( 1-30 days no evidence of increased susceptibility. a dermal assessment is not needed. 

and 1-6 months) 

OAEL = 32 90-Day om! toxicity (dog) 

Inhalation mg/kg/day UFA= IOX LOAEL -= 72 mg/kg/day [F] 

Shon-and UFtt = !OX Occupational I based on depressed RBC 

Intermediate- Inhalation toxicity is FQPA SF = IX Residential LOC for parameters (red blood cell count. 

Term ( 1-30 days considered equivalent MOE = 100 hemoglobin level and 

and 1-6 months) to oral toxicity. hematocrit). thymus atrophy and 

decreased food consumption. 

Cancer (oral. Classification: .. not likely to be carcinogenic 10 humans .. based on lack of evidence of carcinogenicity 

dem1al. inhalation) in rats and mice. 

Abbrevinuons: UF = uncenamt)' factor. UF,. =extrapolation from ammal to human (mtcrspec1es). UF" =potential vanauon in sensitivity among 

members ofihc human population (intraspccics), FQPA SF ~ FQPA Safe!)' Factor. NOAEL • no-observed advcrsc-cITect level. LOAEL = 

lowest-observed adverse·eITect level. MOE= margin of exposure. LOC = level cf concern. 

Body Weight 

Since the inhalation POD is not based on developmental and/or fetal effects, the body weight 

appropriate for inhalation assessments is 80 kg. 

Page 6of13 
4.0 Proposed Use Profile 

Bayer CropScience has submitted a draft label for 14ACP703 SC Insecticide/Miticide (EPA Reg. 

#432-xxxx). Information pertaining to the proposed end-use product is listed in Table 3.3. 

There are no required label changes at this time. 

Table 3.3. Summary of Directions for Use of Spirotetramat. 

Applic. Timing, Formulation Applic. Rate (lb Max. No. Max. Yearly 

Type. and [EPA Reg. o.] ai/A) Applic. per Year Applic. Rate (lb Use Directions and Limitations 

Equip. ai/A) 

Residentia l Citrus Trees 

10 n ov A = 0. 156 

Apply to ful l- lb ai/A 

size mature Soluble 

trees Concentrate 4.25 fl oz/100 gal 

Do not apply within I 0 days 

[432-xxxx] prior to bloom. during bloom. = 0.066 lb ai/100 2 20 n ov A = or until petal fall is complete. 

Foliar gal 0.32 lb ai/A 

application 2 lb ai/gal Rctreauncnl interval = 21 days using handhe ld 22.4% ai 0.23 n oz/1000 fl2 sprayers = 0.0036 lb 

ai/I 000 ft2 

5.0 Residential Exposure and Risk Estimates 

There is the potential for residential short-term handler and post-application dermal and 

inhalation exposure from the proposed use on residential ornamentals; however, since a dermal 

POD has not been selected for spirotetramat, a quantitative assessment of dermal risk was not 

conducted. 

5.1 Residential Handler Exposure/Risk Estimates 

HED uses the term "handlers" to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment. 

The quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios: (1) mixing/loading/applying a liquid formulation using a manuallypressurized handwand, (2) mixing/loading/applying a liquid formulation using a hose-end 

sprayer, and (3) mixing/loading/applying a liquid formulation using a backpack sprayer. 

Residential Handler Exposure Data and Assumptions 

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Each assumption and factor is detailed below. 

Page 7of 13 
Application Rate: Maximum application rates, as outlined in Table 3.3, were used to assessed 

residential handler exposure. 

Unit Exposures and Area Treated or Amount Handled: Unit exposure values and estimates for 

area treated or amount handled were taken from HED's 2012 Residential SOPs2

• 

Exposure Dural ion: Although the product can be applied every 21 days, a maximum of only 2 

applications can be made per year; therefore, only short-term residential handler exposure was 

assessed. 

Residential Handler Non-Cancer Exposure and Risk Estimate Equations 

The algorithms used to estimate exposure and dose for residential handlers can be found in 

Appendix A and/or the 2012 Residential S0Ps

3

. 

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates 

The residential handler exposure and risk estimate indicates that the short-term inhalation MO Es 

are not of concern to HED (i.e., MOE::::_ 100). 

Table 5.1. Residential Handler Non-cancer Exposure and Risk Estimates for S1>irotetramat. 

Inhalation Unit Maximum Amount Inhalation 

Level of (LOC = 100) Exposure Scenario Concern Exposure Appl ication Handled Dose (mg/lb ai) Rate1 Oaily2 

(mg/kg/day)3 MOE4 

Mix er/Loader/ Aoolicator 

Manuallypressurized 0.018 0.00066 5 0.00000074 43,000,000 

hand wand 100 

Hose-end sprayer 0.0014 0.00066 II 0.00000013 250,000,000 

Backpack sprayer 0.14 0.00066 5 0.0000058 5,500.000 1 Based on proposed loocl (EPA Reg. #432-xxxx). 2 Based on HED"s 2012 Residential SOPs (http://www e11a,gov/pcsticides/scicncc/residential-exnQsurc-sop.html). 

l Inhalation Dose = lnhalatim Uni I Exposure (mg/lb ai) x Application Rate (lb ai/gal) x Amount I land led (gallons/day) + Body Weight (ID kg). 

• Inhalation MOE = Inhalation NOAEL (32 mg/kg/day) + Inhalation Dose (mg/kg/day). 

5.2 Residential Post-application Exposure/Risk Estimates 

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with spirotetramat. For the spirotetramat 

proposed use on residential citrus trees, there would be the potential for dermal exposure for 

adults and children (6 to <11 years old); however, since there is no dermal POD, a quantitative 

assessment of dermal risk is not necessary and has not been conducted. Post-application 

inhalation exposure while performing activities in previously treated gardens or trees has not 

been quantitatively assessed due to the combination of low vapor pressure for spirotetramat (1.5 

x 1 o·8 Pa at 25°C) and the expected dilution in outdoor air. 

2 Available: htlp://www.epa.gov/pesticides/science/residential-cxposure-sop.html 

3 Available: htto://www .epa.gov/pesticides/science/resident ial-exposure-sop.htm I 

Page 8of13 
5.3 Residential Risk Estimates for Use in Aggregate Assessment 

Table 5.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for spirotetramat. 

• The recommended residential exposure for use in the adult aggregate assessment reflects 

handler inhalation exposure when using a backpack sprayer. 

Table 5.3.1. Recommendations for the Residential Exposures for the Spirotetramat Aggregate Assessment. 

Lifestage Dose (mg/kg/day)1 MOE2 

(Scenario) Dermal Inhalation Oral Total Dermal Inhalation Oral Total 

Adult 

(Backpack Sprayer) NA 

Short-term Residential Handler 

0.0000058 NA 0.0000058 NA 

1 Dose= the highest dose for each applicable lifcstage of all scenarios assessed from Table 61. I. 2 MOE= the MOEs associated with the highest doses identified in Table 6.1. 

6.0 Occupational Exposure and Risk Estimates 

6.1 Occupational Handler Exposure/Risk Estimates 

5,500,000 NA 5,500,000 

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: ( 1) mixing/loading/applying a liquid formulation using a manuallypressurized handwand, (2) mixing/loading/applying a liquid formulation using a mechanicallypressurized handgun, and (3) mixing/loading/applying a liquid formulation using a backpack 

sprayer. 

Occupational Handler Exposure Data and Assumptions 

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis. 

Application Rate: Maximum application rates, as outlined in Table 3.3, were used to assessed 

occupational handler exposure. 

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific. data, 

Page 9 of 13 
include PHED 1.1, the AHETF database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data 

protection provisions of FTFRA. The standard values recommended for use in predicting handler 

exposure that are used in this assessment, known as "unit exposures", are outlined in the 

"Occupational Pesticide Handler Unit Exposure Surrogate Reference Table4", which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website5

. 

Area Treated or Amount Handled: An estimate of 40 and 1000 gallons handled/day was used in 

the occupational handler exposure calculations for backpack/manually-pressurized handwands 

and mechanically-pressurized handguns, respectively, based on guidance in ExpoSAC Policy 

9.1. 

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 

days to six months as intermediate-term. Exposure duration is determined by many things, 

including the exposed population, the use site, the pest pressure triggering the use of the 

pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

reasonable to believe that occupational handlers will not apply the same chemical every day for 

more than a one-month time frame; however, there may be a large agribusiness and/or 

commercial applicators who may apply a product over a period of weeks (e.g., completing 

multiple applications for multiple clients within a region). 

For spirotetramat, based on the proposed use, short- and intermediate-term exposures are 

expected since there is the potential for multiple applications at the maximum application rate. 

The proposed label is for use on residential citrus trees, and the product could be used by 

professional applicators for multiple clients. The label does state that the product can be applied 

up to 2 times per year with a 21 day interval. It should also be noted that for spirotetramat, both 

the short- and intermediate-term PO Os are the same; therefore, estimates of short-term 

exposure/risk are protective of any repeated exposure for longer than 30 days. 

Mitigation/Personal Protective Equipment: The proposed product label for this use recommends 

that applicators and other handler must wear protective eyewear, long-sleeved shirts and long 

pants, chemical-resistant gloves, and shoes plus socks. 

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations 

The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates 

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm inhalation MO Es are not of concern to HED (i.e., MOE ~ l 00). 

4 Available: http://www.epa.gov/oppOOOO I /science/handler-exposure-table.pdf 5 A vai I able: http://www.epa.gov/pesticides/science/handler-exposure-data.htm I 

Page 10of13 
Table 6. 1. 1. Occupational Ha ndler Non-Cancer Exposure a nd Risk Estimates fo r Spirotetra mat. 

Inhalation Unit Inhalation Exposure Maximum Amount Handled (LOC = 100) Exposure ccnario Crop or Target (ul!/lb ai)1 

Application Ratc2 Oaily3 

Dose Mitigation Level (mj!,/kg/day)4 MOE5 

Mix er/loader/ A ool icator 

Manual ly-prcssurized 140 handwand for fo liar (baseline) 40 0.0000463 690,000 

applications 

Backpack sprayer for Residential 30 0.00066 40 0.0000099 3,200.000 foliar annlications Citrus trees (baseline) 

Mechanically- 3.9 pressurized handgun for (baseline) IOOO 0.000032 1 1,000,000 

fol iar applications 1 . . .. Based on lhe '"Occupational Pesuc1dc Handler U111t Exposure Surrogate Reference Table" (May20 13); Level of 1111t1 gat1on: Baseline (longsleeved shirt. long pants, shoes plus socks). 

Based on proposed looel (EPA Reg.# 432-xxxx). 1 Exposure Science Advisory Council Policy 119. l. 

' Inhalation Dose = lnhalatiCll Unit Exposure (μg/lb ai) x Conversion Factor (0.001 mg/11g) x Application Rate (lb ai/gal) x Amount Handled 

(gal/day) + BW (80 kg). 

~ Inhalation MOE = Inhalation NOAF.L (32 mg/kg/day)+ Inhalation Dose (mg/kg/day). 

6.2 Occupational Post-application Exposure/Risk Estimates 

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). For the proposed use of spirotetrarnat, occupational post-application exposure 

is not anticipated since the use is on residential citrus trees. Professional applicators would not 

be expected to return to a residential area to perform functions associated with previously treated 

residential citrus trees. Therefore, a quantitative occupational post-application assessment was 

not conducted. 

Page 11 of 13 
Appendix A. Summary of Occupational and Residential Non-cancer Algorithms 

R ESIDENTIAL NON-CANCER H ANDLER ALGORITHMS 

Gardens and Trees -- Inhalation Handler Exposure Algorithm 

Daily inhalation exposure (mg/day) for residential pesticide handlers, for a given formulationapplication method combination, is estimated by multiplying the formulation-application 

method-specific unit exposure by an estimate of the amount of active ingredient handled in a 

day, using the equation below: 

E = UE *AR* A 

where: 

E = exposure (mg/day); 

UE = unit exposure (mg/lb ai); 

AR = application rate (e.g., lb ai/ft2, lb ai/gal); and 

A = area treated or amount handled (e.g., ft2/day, gal/day). 

O CCUPATIONAL NON-CANCER H ANDLER ALGORITHMS 

Potential daily exposures for occupational handlers are calculated using the following formulas: 

where: 

E 

UE 

AR 

A 

= 

= 

= 

E=UE *AR* A * 0.001 mg!ug 

exposure (mg ai/day), 

unit exposure (μg ai/lb ai), 

maximum application rate according to proposed label (lb ai A or lb ai/gal), and 

area treated or amount handled (e.g., Alday, gal/day). 

The daily doses are calculated using the following formula: 

where: 

ADD = 

E 

AF = 

BW 

ADD= 

E*AF 

BW 

average daily dose absorbed in a given scenario (mg ai/kg/day), 

exposure (mg ai/day), 

absorption factor (dermal and/or inhalation), and 

body weight (kg). 

Page 12 of 13 
Margin of Exposure: Non-cancer risk estimates for each application handler scenario are 

calculated using a Margin of Exposure (MOE), whjch is a ratio of the toxicological endpoint to 

the daily dose of concern. The daily dermal and inhalation dose received by occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula: 

where: 

MOE 

POD = 

ADD = 

POD 

MOE= -

ADD 

margin of exposure: value used by HED to represent risk estimates (urutless), 

point of departure (mg/kg/day), and 

average daily dose absorbed in a given scenario (mg ai/kg/day). 

Page 13 of 13