UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D

. C. 20460

Date:

Subject: September 12, 2013 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### Propoxur. Occupationa l and Residential Exposure Assessment in Response to the Natural Resources Defense Council Petition for Pet Collars

PC Code: 04 7802 Decision No.: 469552 Petition No.: NA DP Barcode: 0405246 Registration No.: NA Regulatory Action: Petition Response Case No.: NA Risk Assessment Type: Occupational/Residentia l Exposure Assessment TXRNo.:NA CAS No.: 114-26-1 M RI DNo.: NA



### From:

T hrough:

To:

Introduction 40CFR:NA

Shalu Shelat

, Industrial Hygienist

# 1)\A**~ ~**  "\Jl \'1.-\.rJ

Risk Assessment Branch VI Heal t h Effects Division (7509P)



### Felec i a Fort, Branch Chief

# ~- • C(, 

# r ;/- 'f 

# /J');/ /.3

Risk Assessment Branch VI

# ~**~** Health Effects Division (7509P)

and

Alexandra Lamay

, ExpoSAC Designated Reviewer 

# tf

# ~ AV Kelly 

### 0' Rouke, ExpoSAC Designated Reviewer

# ~1'1.,4>~~ E xposure Science Advisory Committee (ExpoSAC) I 

## HED

Kaitlin Keller
Risk Management and Implementation Branch 3 Pesticide Re

- Evaluation Division (7508P)

The purpose of this document is to provide an exposure and risk assessment for the insecticide
active ingredient, propoxur, as it is formulated in pet collar products

. This assessment has been
conduc t ed as a response to a petition submitted by the Natural Resources Defense Council 

### (NRDC) and posted in the public docket 

### (EPA-HQ-OPP -2 009

- 0207)

. The exposure es t imates for propoxur use in pet collars had been previously addressed as part of the N

- Methyl Carbamate

Page I of25Cumulative Risk Assessment (2007) and most recent l y in 201 0 in response to the NRDC petition (D371250 and D379902; S

. Shelat). The current assessment is a reevaluation of the previous pet collar assessment to include propoxur data t ha t has been recently submitted to the Agency. The

assessment incorporates a propoxur Comparative Cholinesterase Assay (TXR# 0056440) and a propoxur Pet Collar Residue Transfer Study (S. She l at, D393899; 10 / 12112).

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 Residential SOPs (Residential Handler and Treate d Pets SOP) as well as a registrant-submitted residue transfer study (MRID 48589903). 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) August 1

, 2013

Page 2 of25Page 3 of 25 

### Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4 2.0 Risk Assessment Conclusions and Recommendations

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

................................ ................................ ............................. 6 2.2 Label Recommendations from Occupational Assessment

................................ ............... 6 2.3 Label Recomm endations from Residential Assessment

................................ .................. 6 2.4 Data Deficiencies and Requirements

................................ ................................ ............... 6 3.0 Hazard Characterization

................................ ................................ ................................ ....... 6 4.0 Us e Profile

................................ ................................ ................................ ........................... 8 5.0 Residential Exposure and Risk Estimates

................................ ................................ ............ 9 5.1 Residential Handler Exposure/Risk Estimates

................................ ................................ . 9 5.2 Residential Post

- application Exposure/Risk Estimates

................................ .................. 11 5.3 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 14 5.4 Spray Drift

................................ ................................ ................................ ...................... 17 5.5 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 17 6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 17 6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 17 6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 20 Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

..................... 21 Appendix B. Summary of Occupational and Residential Cancer Algorithms

............................. 25Page 4 of 25



### 1.0 Executive Summary

Propoxur [o

- isoprop oxyphenyl methylcarbamate ] is a carbamate insecticide with a number of currently active labels for use by pest control operators to control ants, roaches, hornets, and other pests in and around commercial, industrial, and institutional buildings as well as in food handling establishments and outside residences

. Propoxur may also be used by homeowners in granular, paste, and impregnated formulations ( i.e., pet collars and bait strips) of the insecticide. It was first registered in 1963

. E xposures to propo xur can be expected to occur via the occupational and residential handler and post

- application routes of exposure.

T he tox icology database for propoxur is complete as described in 40 CFR, Part 158. As with other NMCs

, propoxur inhibits acetylcholinestera se (AChE) by carbamylation of the serine hydroxyl group located in the active site of the enzyme . Toxicological characteristic s of

propoxur , like the other NMCs involves maximal ChE inhibition ( within 15 minutes for adults and 30 minutes for post

- natal day 11 pups) followed by rapid reactivation of the enzyme and then recovery ( 4 hours for adults, and longer for PND11 pups) . As such, the critical duration of exposure for propoxur is acute ChE inhibition of brain and RBC AChE measured at the peak time of ef fect. EPA used the same benchmark dose ( BMD ) modeling approach that was developed for the OP cumulative risk assessment to assess the N

- Methyl carbamate s

.
A BMD analysis was conducted for both oral and inhalation endpoints. The acute oral Point of Departure (PoD) is based on a BMDL 10 

### of 0.0285 mg/kg/day for RBC ChE inhibition at the peak time of inhibition (30 minutes) in male and female PND11 pups (combined) in the acute comparative cholinesterase assay (CCA) . The inhalation POD is based on a BMDL 10 

### of 0.0076 mg/L (residential human equivalent dose of 1.67 mg/kg) for brain ChE inhibition in female adults in a chronic inhalation toxicity study. No dermal risks are expected from dermal exposure of any duration because no adverse effects were observ ed at the highest dose tested (1000 mg/kg/day) in a 90 day dermal toxicity study. Propoxur is classified as a Group B2: Probable human carcinogen by the U.S. EPA with a linear low

- dose approach for quantification of risk using the oral slope factor (Q 1 

### *) o f 3.52 x 10 - 3 

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

### . However, this linear low

dose approach was based on concentrations of exposure that were orders of magnitudes greater than what is currently allowable for propoxur.

The recently submitted acute CCA study indicates that PND 11 pups are more sensitive than the adult rats for brain and RBC cholinesterase inhibition (combined sex data). However, there is no evidence of i ncreased quantitative susceptibility in the rat and rabbit developmental toxicity studies, or the 2

- generation reproductive studies. Although there was an increase in susceptibility in the CCA study, HED’s degree of concern for the susceptibility observed is low because the oral regulatory endpoints for propoxur are based on the PND11 pup BMDL10 for RBC ChE inhibit ion. Therefore, HED concluded that the 10x FQPA Safety Factor could be reduced to 1x for oral exposure. However, for residential inhalation exposures, HED is incorporating a data

derived FQPA safety factor based on the relative sensitivity of pups versus adults for RBC CHE inhibition in the CCA study. This factor is necessary to protect sensitive lifestages because the inhalation POD is based on brain ChE inhibition in adult animals.Page 5 of 25



### Dermal risk estimates for children (1 < 2 years old) and adults were n ot assessed because no endpoints have been identified for dermal exposure. Inhalation risk estimates for children (1 < 2 years old) and adults have also not been assessed because inhalation exposure from applying a collar to a pet or companion animal is c onsidered to be negligible based on the nature of the propoxur impregnated collar. Incidental oral ingestion (hand to mouth) risk estimates were assessed for children (1 < 2 years old). Exposure via hand to mouth is a viable route of exposure for children coming into contact with a pet or companion animal that has been treated with a propoxur impregnated pet collar.

Residential post

- application risk from exposure to the propoxur pet collar was assessed using the Standard Operating Procedures (SOPs) fo r Residential Pesticide Exposure Assessment (2012) 1 

### along with propoxur specific pet collar data submitted by the registrant ( Determination of Transferable Residues of Propoxur from the Hair of Dogs Wearing Collars Impregnated with Propoxur, MRID 48589903) . HED has also received information from Wellmark, Inc and Sergeants Pet Care Products detailing the range of marketed collar sizes that are currently registered for both dogs and cats.

Based on the Agency's current practices, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for propoxur at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for propoxur

.
Occupational handler dermal cancer risk estimates range from 4E

- 07 to 1E

- 06. The residential handler cancer dermal risk estimates range from 3E

- 08 to 1E

- 07. The residential post

application dermal cancer risk estimates range from 4E

- 07 to 1E

- 06 and 8E

- 07 to 2E

- 06 for the 180 and 365 day exposure periods, respective ly. Non

- cancer risk estimates for the post

application incidental oral ingestion route of exposure result in risk estimates that exceed HED’s level of concern (MOEs <100) ranging from 37 to 120.

Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include the Residential SOPs (Residential Handler and Treated Pets SOP) as well as registrant

- submitted residue transfer study (MRID 48589903 ) are (1) subject to ethics 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 Human Studies Review B oard. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 2



### .

2.0 Risk Assessment Conclusions and Recommendations

No data gaps have been identified for propoxur at this time.

1 http://www.epa.gov/pesticides/science/EPA

- OPP

- HED_Residential%20SOPS_Feb2012.pdf

2 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.htmlPage 6 of 25



### 2.1 Summary of Risk Estimates

2.2 Label Recommendations from Occupational Assessment

HED has n o label recommendations based on the occupational assessment.

2.3 Label Recommendations from Residential Assessment

HED has n o label recommendations based on the residential assessment. It should be noted that there are risks of concern (MOEs < 100) for propoxur impregnated collars ranging from an MOE of 37 to 85 for the small, medium, and large cat collars and small, medium dog collars . (See Section 5.2)

2.4 Data Deficiencies and Requirements

There are no data deficiencies or requirements identified for propoxur at this time.

3 .0 Hazard Characterization

Acute Toxicity

Propoxur is in the tox icity category II by oral route, and category III by dermal and inhalation

routes. Prop oxur is a mild irritant to the eyes of rabbits (Toxicity Category III), but is not a dermal irritant (category IV), or dermal sensitizer.

Table 4

. 3

. 1 Acute Toxicity Profile

Guideline No. Study Type Results Toxicity Category

870.1100 Acute oral [rat] LD 50 (M) = 94 mg/kg

LD 50 (F) = 68 mg/kg II

870.1200 Acute dermal [rabbit] LD 50 : >2000 mg/kg III

870.1300 Acute inhalation [rat] LC 50 >0.498 mg/L III

870.2400 Acute eye irritation [rabbit] Mild Irritant III

870.2500 Acute dermal irritation [rabbit] No Irritation IV

870.2600 Skin sensitization [guinea pig] Non sensitizer N/A



### Toxicological PODs Used for Risk Assessment

The toxicology database is complete for propoxur . The toxicity profile can be characterized for all effects, including potential neurotoxicity, developmental and reproductive toxicity, and immunotoxicity. Acceptable studies for developmental toxicity in rats and rabbits, 2

- generation reproduction in rats, a comparative cholinesterase assay (CCA) and neurotoxicity are available.Page 7 of 25



### A BMD analysis was conducted for both oral and inhalation endpoints. The acute oral Point of Departure (PoD) is based on a BMDL 10 

### of 0.0285 mg/kg/day for RBC ChE inhibition at the peak time of inhibition (30 minutes) in male and female PND11 pups (combined ) in the acute comparative cholinesterase assay (CCA) . The inhalation POD is based on a BMDL 10 

### of 0.0076 mg/L (residential human equivalent dose of 1.67 mg/kg) for brain ChE inhibition in female adults in a chronic inhalation toxicity study. No dermal risks are expected from dermal exposure of any duration because no adverse effects were observed at the highest dose tested (1000 mg/kg/day) in a 90 day dermal toxicity study. Propoxur is classified as a Group B2: Probable human carcinogen by the U.S. EPA with a linear low

- dose approach for quantification of risk using the oral slope factor (Q 1 

### *) of 3.52 x 10 - 3 

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



### .

Table 4

. 3

. 2 Summary of Toxicological Doses and Endpoints for Propoxur for Use in Dietary and Non

Occupational Human Health Risk A ssessments

Exposure/ Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Incidental Oral Acute BMDL 10 =

0.0285 mg/kg/day UF A = 10 x

UF H = 10 x FQPA SF= 1 x Acute RfD = aPAD =0.000285 mg/kg/day Acute comparative cholinesterase assay

( MRID 48784802, 48784803 BMD 10 =

0.0427 mg/kg/day
BMDL 10 = 0.0285 mg/kg/day based on RBC ChE inhibition in male and female PND11 pups (combined)

Inhalation Acute BMDL 10

F= 0.0076 mg/L

Residential HEC = 1.67 mg/kg; 7 mg/m 3 ; 0.007 mg/L UF A = 3X

UF H = 10X FQPA SF= 11X Residential

(children) LOC= 330 Residential (adult) LOC= 30 Chronic inhalation study

- Rats (MRID 42648001; 40836402)

BMD 10 F= 0.0095 mg/L
BMDL 10 F = 0.0076 mg/L based on ChE

in the brain
BMD 10 M= 0.016 mg/L
BMDL 10 M = 0.011 mg/L based on ChE

in the brain

Dermal A risk assessment for dermal exposure of any duration is not required as no adverse effects were observed at the highest dose tested (1000 mg/kg/day) (MRID 41066001).

Cancer (oral, dermal, inhalation) Classification: Group B2; “ Probable Human Carcinogenic ” based on dose

- related and highly

significant increased incidence of urinary bladder papillomas and carcinomas in both sexes, and a borderline statistically significant increased incidence of uterine carcinoma s in high

- dose females

(MRID 00142725). The Q 1 * is 3. 52 x 10 - 3 (mg/kg/day 

### )

.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. LOC = level of concern.



### AbsorptionPage 8 of 25



### A dermal absorption factor of 19.6 % was used for th e exposure assessment (MRID 43736616)

. A bsorption by the inhalation route is considered to be equivalent to the estimated toxicit y by the oral route of exposure, however, inhalation exposure is considered to be negligible based on the nature of the propoxur impregnated collar.

Body Weight The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal effects.

4 .0 Use Pro file

There are a number of cur rently active labels registered for propoxur to control ants, roaches, hornets, and other pests in and around commercial, industrial, and institutional buildings as well as in food handling establishments and outside residen ces. Propoxur is also registered as granular and impregnated formulations (i.e., pet collars and ba it strips) of the insecticide. This document assesses the impregnated pet collar formulations of propoxur as listed below in Table 4.1.

Table 4 .1. Summary of Registered Propoxur Pet Collars

Applic. Type Formulation

[EPA Reg. No.] Weight

of Collar (grams

per collar) % Active

Ingredient Applic. Rate

(mg ai per collar ) Use Directions and

Limitations

Wellmark International

Small Dog 2724

- 254 ,

2724

- 493 19.8

10% 1980

Buckle collar around dog’s/puppy’ /cat’s neck. Fit to size. Leave 2

- 3 / 1

- 2 extra inches on the collar for adjustment, cut off excess length and dispose of in trash. (Up to 5 to 8 months) Medium Dog 2724

- 254 ,

2724

- 493 34 3400

Large Dog 2724

- 254 ,

2724

- 493 34 3400

Small Cat 2724

- 275,

2724

- 491 10.5 1050

Medium Cat 2724

- 275,

2724

- 491 10.5 1050

Large Cat 2724

- 275,

2724

- 491 10.5 1050

Sergeants Pet Care Products, Inc

Small Dog 2517

- 61

2517

- 144 19

9% 1710 Place collar around pet’s neck, adjust for fit, and buckle in place.

Leave 2 or 3 inches for extra adjustment. Cut off and dispose of excess length. (Up to 3 to 6 months) Medium Dog 2517

- 61,

2517

- 78

, 2517

- 144 28.5 2565

Large Dog 2517

- 61,

2517

- 144

, 2517

- 144 32.1 2889Page 9 of 25

Table 4 .1. Summary of Registered Propoxur Pet Collars

Applic. Type Formulation

[EPA Reg. No.] Weight

of Collar (grams

per collar) % Active

Ingredient Applic. Rate

(mg ai per collar ) Use Directions and

Limitations

Small Cat 2517

- 61,

2517

- 144 14 1260

Medium Cat 2517

- 78

,

2517

- 144 16.3 1467

Large Cat 2517

- 78

,

2517

- 144 16.3 1467



### 5 .0 Residential Exposure and Risk Estimates

This assessment addresses the exposure and risk estimates from non

- occupational handler and post

- application exposures of propoxur through the dermal, inhalation, and incidental oral ingestion routes of exposure related to the impregnated pet collar use. R e sidential uses have been assessed in this document to reflect updates to HED’s 2012 Residential SOPs 3 

### along with policy changes for body weight assumptions. Additionally, the assessment incorporates recently submitted chemical specific comparative cholinesterase assay ( MRID 48784802 ) and residue transfer study ( MRID 48589903 ).

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 t hat 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:

Applying propoxur impregnated pet collars to companion animals

Residential Handler Exposure Data and Assumptions A series of assumptions and exposure fact ors served as the basis for completing the residential handler risk assessments. Each assumption and factor is detailed below.

Application Rate : Application rates for the propoxur impregnated collars vary with the size of the marketed collars and are stated in Table 4.1.

3 Available: http://www.epa.g ov/pesticides/science/residential

- exposure

- sop.htmlPage 10 of 25



### 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 SOPs 4



### .

Exposure Duration: Residential handler exposure is expected to be short

- term in duration. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners

.

Days P er Y

ear of Exposure: Residential handler exposure is expected to occur several times per year. The length of t ime a single collar remains efficacious on the companion animals ranges from 3 to 8 months , thus a residential handler would re

- apply the collar 2

- 4 times per year

. As a conservative assumption i t is assumed that residential handlers would be exposed for 4 days out of 365 days per year . This assumption is determined by the efficacious lifetime of the collar.

Years P er Lifetime of Exposure: It is assumed that residential handlers would be exposed for 50 years out of a 78 year lifespan.

Lifetime Expectan cy: Life expectancy values are from the Exposure Factors Handbook 2011 Edition Table 18

- 1 (U.S. EPA, 2011). The table shows that the overall life expectancy is 78 years based on life expectancy data from 2007. In 2007, the average life expectancy for mal es was 75 years and 80 years for females. Based on the available data, the recommended value for use in cancer risk assessments is 78 years.

Residential Handler 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 SOPs 5



### . Combining Exposures/Risk Estimate s: D ermal and inhalation risk estimate s were not combined in this assessment, since no toxicological effects were determined from the dermal exposure study

. I nhalation risk estimates

are not provided because exposure from the inhalation route is considered negligible for the companion animal pet collar scenario.

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates

No dermal non

- cancer risks are expected from dermal exposure of any duration because no adverse effects were observed at the highest dose tested (1000 mg/kg/day) in a 90 day dermal toxicity study; therefore, a quantitative non

- cancer dermal assessment was not completed for the

propoxur . Additionally, exposure is considered to be negligible from the inhalation route for the impregnated collar scenario, therefore a non

- cancer inhalation assessment was also no t completed for this use.

4 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

5 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 11 of 25



### Residential Handler Cancer Exposure and Risk Estimate Equations A Q 1 * 

### was identified for propoxur based on dose

- related and highly significant increased incidence of urinary bladder papillomas and carcinomas in both sexes, and a borderline statistically significant increased incidence of uterine carcinomas in high

- dose females

. Although a non

- cancer dermal risk assessment was not performed due to the lack of an adverse affect in the non

- cancer dermal study , a dermal cancer exp osure and risk assessment was performed because dermal exposure does contribute to the overall cancer risk for propoxur. Dermal exposure s were calculated based on the use pattern and algorithms as provided in the 2012 Residential SOPs. The calculated der mal average daily dose was used to determine the Lifetime Average Daily Dose (LADD ). The LADD represents the overall lifetime exposure and dose which is utilized in the cancer risk assessment. Cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a LADD is first calculated and then compared with a Q 1 

### * that has been calculated for propoxur based on dose response data in the appropriate toxicology study (Q 1 

### * = 3.52x10 - 3 

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

### ). The algorithms used to estimate the LADD and cancer risk for residential handlers can be found in Appendix B

.
Summary of Residential Handler Cancer Exposure and Risk Estimates A cancer dermal assessment was completed for propoxur. The cancer risk estimates for the dermal route of exposure ranged from 3 E

- 08 to 1E

- 07

.

Table 5.1. 1 . Residential Handler Cancer Exposure and Risk Estimates for Propoxur

.
Exposure Scenario LADD (mg/kg/day) Cancer Risk Estimate 2

Dermal 1 Q 1 * = 3.52 x10 - 3

Wellmark International Small Dog Collar 1.8E

- 05 6 E

- 08 Medium Dog Collar 3.1E

- 05 1 E

- 07 Large Dog Collar 3.1E

- 05 1 E

- 07 Small Cat Collar 9.5E

- 06 3 E

- 08 Medium Cat Collar 9.5E

- 06 3 E

- 08 Large Cat Collar 9.5E

- 06 3 E

- 08 Sergeant’s Pet Care Product s, Inc Small Dog Collar 1.6E

- 05 6 E

- 08 Medium Dog Collar 2.3E

- 05 8 E

- 08 Large Dog Collar 2.6E

- 05 9 E

- 08 Small Cat Collar 1.1E

- 05 4 E

- 08 Medium Cat Collar 1.3E

- 05 5 E

- 08 Large Cat Collar 1.3E

- 05 5 E

- 08

1 Dermal LADD (mg/kg/day) = Dermal dose (mg/kg/day) × [Days per year of exposure ( 4 days/yr) ÷ 365 days/year] × [ 50 Years per lifetime of exposure (yrs) ÷ Lifetime expectancy ( 78 yrs)]. 2 Cancer risk estimates = Total LADD (mg/kg/day) * Q 1 * , where Q 1 * = 3.52x10 - 3 (mg/kg/day)

- 1

.



### 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 propoxur

. The quantitative exposure/risk

assessment for residential post

- application exposures is based on the following scenarios:
Post

- application dermal exposures from treated pets for adults and children 1<2 years old
Post

- application incidental oral exposure from treated pets for children 1<2 years oldPage 12 of 25



### The lifestages selected for each post

- application scenario are based on an analysis provided as an Appendix in the 2012 Residential SOPs 6 

### . These lifestages are not the only lifestages that could be potentially exposed for these post

- application scenarios; however, the assessment of these lifestages is health protective for the exposures and risk estimates for any other potentially exposed lifestages.

Residential Post

- application Exposure Data and Assumptions A series of assumptions and exposure factors se rved as the basis for completing the residential post

- application risk assessment . Each assumption and factor is detailed in the 2012 Residential SOPs 6



### . In addition to the standard assumptions as detailed in the SOPs, a propoxur

- specific Transferable Residue study from the hair of dogs wearing collars impregnated with propoxur (MRID 48589903) has been submitted to the Agency. Review of the study data provided results in a 0.072% Fraction of Available Residue (FAR) (D393899, S. Shelat, 10/12/2012). The 0.072% FAR was calculated based on the four hour sample for Day 0 after treatment in the Transferable Residue Study. The four hour Day 0 sample wa s the most appropriate for th e non

cancer assessment

. The 0.072% value was used in lieu of the default 2% FAR as stated in the 2012 Residential SOPs

. An FAR of 0.013% wa s utilized in the cancer post

- application assessment to represent a year

- long exposure period (365 days). The 0.013% FAR was derived as the FAR over the course of the 28 days study through a regression analysis.

Days P er Y

ear of Exposure: Residential p ost

- application exposure is expected occur throughout the year. The length of time a single collar remains efficacious on the companion animals ranges from 3 to 8 months. It is assumed that the potential for residential post

- application exposure may be u p to a year round

exposure because collars may be replaced several times a year as their lifetime expires or the exposure duration may be less as pest pressures change . Based on this use pattern, the residential

cancer post

- application scenario assumes ex posure for 180 days and 365 days per year to represent both partial and full year exposure to companion animal collars

.

Years P er Lifetime of Exposure: It is assumed that residential post

- application exposure would occur for 50 years out of a 78 year life span.

Lifetime Expectancy: Life expectancy values are from the Exposure Factors Handbook 2011 Edition Table 18

- 1 (U.S. EPA, 2011). The table shows that the overall life expectancy is 78 years based on life expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and 80 years for females. Based on the available data, the recommended value for use in cancer risk assessments is 78 years.

Residential Post

- application Non

- Cancer Exposure and Risk Equations The algorithms used to estimate residential post

- application exposure and dose can be found in Appendix A and/or the 2012 Residential SOPs 6



### .

6 Available: http://www.epa.gov/pesticides/science/r esidential

- exposure

- sop.htmlPage 13 of 25



### Combi ning Exposure and Risk Estimates Dermal and incidenta l oral r isk estimate s were not combined in this assessment, since no toxicological effects were determined from the dermal exposure route . Therefore, the incidental oral exposures via hand to mouth, is the only applicable route of the non

- cancer exposure and risk assessment for the treated pets exposure scenario.

Summary of Residential Post

- application Non

- Cancer Exposure and Risk Estimates A non

- cancer dermal assessment for adults and children 1<2 year s old was not performed based on the dermal toxicological information for propoxur ; however, a non

- cancer incidental oral assessment was completed for propoxur. The non

- cancer risk estimates for the oral route of

exposure results in risk estimates of conc ern (MOEs < 100) ranging from 37 to 120.

Table 5.2.1. Residential Post

- application Non

- cancer Hand to Mouth Exposure and Risk Estimates for Propoxur.

Lifestage Post

- application Exposure Scenario Application Rate 1 (mg ai/collar) Dose

(mg/kg/day) 2 MOEs 3 Use Site Route of Exposure

Wellmark International

Child (1< 2 years old) Small Dog Collar

Hand to Mouth 1980 0.0006 47

Medium Dog Collar 3400 0.0004 64 Large Dog Collar 3400 0.0003 100
Small Cat Collar 1050 0.0006 44 Medium Cat Collar 1050 0.0004 74 Large Cat Collar 1050 0.0002 120

Sergeants Pet Care Products, Inc

Child (1< 2 years old) Small Dog Collar

Hand to Mouth 1710 0.0005 55

Medium Dog Collar 2565 0.0003 85 Large Dog Collar 2889 0.0002 120
Small Cat Collar 1260 0.0008 37
Medium Cat Collar 1467 0.0005 53 Large Cat Collar 1467 0.0003 85

1 Based on registered label s as stated in Table 4.1

. 2 Dose (mg/kg/day) equations: provided in Appendix A 3 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).



### Residential Post

- application Cancer Exposure and Risk Estimate Equations As was done for residential handlers, post

- application dermal cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a LADD is first calculated and then compared with a Q 1 

### * that has been calculated for propoxur based on dose response data in the appropriate toxicology study (Q 1 

### * = 3.52x10 - 3 

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

### ). The algorithms used to estimate the LADD and cancer risk for residential post

- application e xposure can be found in Appendix B

.
The adult dermal post

- application cancer risk estimates range from 4E

- 07 to 1E

- 06 and 8E

- 07 to 2E

- 06 for the 180 days and 365 days exposure periods, respectfully

. Tables 5.2.2 and 5.2.3 provide the cancer risk estimates.

Summary of Residential Post

- application Cancer Exposure and Risk EstimatesPage 14 of 25

Table 5.2.2. Residential Post

- application Cancer Exposure and Risk Estimates for Propoxur (180 days)

. Lifestage Post

- application Exposure Scenario LADD (mg/kg/day) 1 Cancer Risk

Estimate 2

Wellmark International

Adult Dermal Small Dog Collar 2.7E

- 04 9E

- 07 Medium Dog Collar 2.0E

- 04 7E

- 07 Large Dog Collar 1.2E

- 04 4E

- 07
Small Cat Collar 2.8E

- 04 1E

- 06
Medium Cat Collar 1.7E

- 04 6E

- 07 Large Cat Collar 1.1E

- 04 4E

- 07 Sergeants Pet Care Products, Inc

Adult Dermal Small Dog Collar 2.3E

- 04 8E

- 07 Medium Dog Collar 1.5E

- 04 5E

- 07 Large Dog Collar 1.1E

- 04 4E

- 07
Small Cat Collar 3.4E

- 04 1E

- 06
Medium Cat Collar 2.4E

- 04 8E

- 07 Large Cat Collar 1.5E

- 04 5E

- 07

1 Dermal LADD (mg/kg/day) = Dermal dose (mg/kg/day) × [Days per year of exposure ( 180 days/yr) ÷ 365 days/year] × [ 50 Years per lifetime of exposure (yrs) ÷ Lifetime expectancy ( 78 yrs)]. 2 Cancer risk estimates = Total LADD × Q 1 * , where Q 1 * = 3.52x10

- 3 (mg /kg/day)

- 1

Table 5.2. 3

. Residential Post

- application Cancer Exposure and Risk Estimates for Propoxur (365 days)

. Lifestage Post

- application Exposure Scenario LADD (mg/kg/day) 1 Cancer Risk

Estimate 2

Wellmark International

Adult Dermal Small Dog Collar 5.4E

- 04 2E

- 06 Medium Dog Collar 4.0E

- 04 1E

- 06 Large Dog Collar 2.5E

- 04 9E

- 07
Small Cat Collar 5.7E

- 04 2E

- 06
Medium Cat Collar 3.4E

- 04 1E

- 06 Large Cat Collar 2.1E

- 04 8E

- 07 Sergeants Pet Care Products, Inc

Adult Dermal Small Dog Collar 4.7E

- 04 2E

- 06 Medium Dog Collar 3.0E

- 04 1E

- 06 Large Dog Collar 2.1E

- 04 8E

- 07
Small Cat Collar 6.9E

- 04 2E

- 06
Medium Cat Collar 4.8E

- 04 2E

- 06 Large Cat Collar 3.0E

- 04 1E

- 06

1 Dermal LADD (mg/kg/day) = Dermal dose (mg/kg/day) × [Days per year of exposure ( 365 days/yr) ÷ 365 days/year] × [ 50 Years per lifetime of exposure (yrs) ÷ Lifetime expectancy ( 78 yrs)]. 2 Cancer risk estimates = Total LADD × Q 1 * , where Q 1 * = 3.52x10

- 3 (mg /kg/day)

- 1



### 5

. 3 Residential Risk Estimates for Use in Aggregate Assessment

Table s 5.2.1 and 5.2.3 reflect the residential risk estimates that are recommended for use in the aggregate assessment that will be conducted as part of the Preliminary Risk Assessment during Registration Review for propoxur

. There is no recommended residential exposure for use in the adult non

- cancer aggregate assessment because no dermal non

- cancer assessment was performed for adults.Page 15 of 25



### The recommended residential exposure for use in the children 1<2 years old non

- cancer aggregate assessment reflects hand

- to

- mouth exposures from post

- ap plication exposure to large dog treated with Wellmark, Inc propoxur impregnated collars (MOE is 100). The recommended residential exposure for use in the adult aggregate cancer assessment reflects dermal exposure from the post

- application exposur e to small cat s with Sergeants Pet Care propoxur impregnated collars (dose is 6.9E

- 04 mg/kg/day ).Page 16 of 25 Table 5

. 3 .1. Recommendations for the Residential Exposures for the Propoxur Aggregate Assessment

. 1

Lifestage Residential Handler Residential Post

- application

Dose (mg/kg/day) 2 MOE Dose (mg/kg/day) 3 MOE 4

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral Total Cancer Exposure Scenarios

Adult 3.1E

- 05 N/A 3.1E

- 05 N/A N/A N/A 6.9 E

- 0 4 N/A N/A 6.9 E

- 0 4 N/A N/A N/A N/A

Short

- Term Exposure Scenarios (non

- cancer)

Child N/A N/A N/A 0.0003 0.0003 N/A N/A 100 100

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed from Table 5.1.1

. Total = dermal + inhalation , if applicable

. 3 Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all sce narios assessed from Table 5.2.1 and 5.2. 3 . Total = dermal + inhalation + incidental oral, where applicable. 4 Residential Post

- application MOE = the MOEs associated with the highest doses identified in Table 5.2.1. Total = 1 ÷ (1/Dermal MOE) + (1/Inhala tion MOE) + (1/Incidental oral MOE) , if applicable

.Page 17 of 25



### 5

. 4 Spray Drift

This assessment is conducted for the p ropoxur end use product formulated as an impregnated pet collar and is un likely to result in spray drift

.

5

. 5 Residential Bystander Post

- Application Inhalation Exposure

A quantitative residential post

- application inhalation exposur e assessment was not performed because the inhalation route of exposure is considered negligible for the compan ion pet collar scenario and would n ot result in bystander inhalation exposure.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HE D 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 potentiall y 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:

Ready to Use Impregnated Flea and Tick Collar Application

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 : Application rates for the propoxur impregnated collars vary with size of target companion animal and are stated in Table 4.1.

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, include a registrant

- submitted occupational exposure studies (MRID 44433303) . Some of the se data are proprietary, and subject to the data protection provisions of FI FRA. 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 SurrogatePage 18 of 25



### Reference Table 7 

### ”, which, along with addit ional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 8



### .

Area Treated or Amount Handled : The amount handled for occupational handlers treating companion animals with propoxur impregnated collars is assumed to be 5 collars per day.

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, incl uding the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultural practices surrounding that use site. For propoxur impregnated collars, i t is reasonable to believe that groomers or veterinary professional s may apply collars to companion animals throughout the year. Although the exposure duration for pet collars can be considered long er

- term, propoxur is part of the N

- methyl carbamate chemical class. Toxicological characteristics of propoxur, like the othe r NMCs involves maximal ChE inhibition (within 15 minutes for adults) followed by rapid reactivation of the enzyme and then recovery (4 hours for adults). Since peak inhibition of cholinesterase occurs rapidly with recovery occurring within hours, the dai ly exposure to propoxur is the main non

- cancer toxicological duration of concern. In this case, we will conduct short

- term scenarios to be protective of the daily exposure duration.

Mitigation/Personal Protective Equipment: Estimates of dermal exposure were calculated for “baseline,” attire defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator

.
Days per Year of Exposure: To assess cance r risk, it is assumed that groomers and veterinary would handle 5 collars per day and be exposed 30 days per year. This would total 150 coll ars handled over the course of one

year.

Years per Lifetime of Exposure: It is assumed that handlers would be expo sed for 35 years out of a 78 year lifespan.

Lifetime Expectancy: Life expectancy values are from the Exposure Factors Handbook 2011 Edition Table 18

- 1 (U.S. EPA, 2011). The table shows that the overall life expectancy is 78 years based on life expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and 80 years for females. Based on the available data, the recommended value for use in cancer risk assessments is 78 years.

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

.
Combining Exposures/ Risk Estimates :

7 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

8 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.htmlPage 19 of 25



### D ermal and inhalation risk estimate s were not combined in this assessment, since no toxicological effects were determined from the dermal exposure study. Inhalation risk estimates are not provided because exposure from the inhalation route is considered negligible for the companion animal pet collar scenario.

Summary of Occupational H andler Non

- Cancer Exposure and Risk Estimates

A dermal and inhalation non

- cancer assessment was not completed based on the information provided abov e.

Occupational Handler Cancer Exposure and Risk Equations A Q 1 * 

### was identified for propoxur based on dose

- related and highly significant increased incidence of urinary bladder papillomas and carcinomas in both sexes, and a borderline statistically significant increased incidence of uterine carcinomas in high

- dose females

. Although a non

- cancer dermal risk a ssessment was not performed due to the lack of an adverse affect in the non

- cancer dermal study, a dermal cancer exposure and risk assessment was performed because dermal exposure does contribute to the overall cancer risk for propoxur. The calculated der mal average daily dose was used to determine the Lifetime Average Daily Dose (LADD ). The LADD represents the overall lifetime exposure and dose which is utilized in the cancer risk assessment. Cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a LADD is first calculated and then compared with a Q 1 

### * that has been calculated for propoxur based on dose response data in the appropriate toxicology study (Q 1 

### * = 3.52x10 - 3 

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

### ). The algorithms used to estimate the LADD and cancer risk for residential handlers can be found in Appendix B.

Summary of Occupational Handler Cancer Exposure and Risk Estimates

A cancer dermal assessment was completed for propoxur. The occupational handler dermal cancer risk estimate s range from 4 E

- 07 to 1 E

- 06

.

Table 6.1.2. Occupational Handler Cancer Exposure and Risk Estimates for Propoxur

.

Exposure Scenario Groomers and Vetrinary Professionals LADD (mg/kg/day) Cancer Risk Estimate 2

Dermal 1 Q* = 3.52 x10 - 3

Wellmark International

Dermal Small Dog Collar 0.000221 8E

- 07

Medium Dog Collar 0.00038 1E

- 06 Large Dog Collar 0.00038 1E

- 06 Small Cat Collar 0.000117 4E

- 07 Medium Cat Collar 0.000117 4E

- 07 Large Cat Collar 0.000117 4E

- 07

Sergeants Pet Care Products, Inc

Dermal Small Dog Collar 0.000191 7E

- 07

Medium Dog Collar 0.000285 1E

- 06 Large Dog Collar 0.000322 1E

- 06 Small Cat Collar 0.000141 5E

- 07 Medium Cat Collar 0.000163 6E

- 07 Large Cat Collar 0.000163 6E

- 07Page 20 of 25

1 Dermal LADD (mg/kg/day) = Dermal dose (mg/kg/day) × [Days per year of exposure ( 30 days/yr) ÷ 365 days/year] × [Years per lifetime of exposure ( 50 yrs) ÷ Lifetime expectancy (yrs)]. 2 Cancer risk estimates = Total LADD × Q 1 * , where Q 1 * = 3.52 x 10 - 3 (mg/kg/day)

- 1



### 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 refe rred to as re

entry exposure). In the case of t he pet collar scenario, it is assumed that occupational (professional groomer or veterinary professional) post

- application activities are expected to be significantly less than residential post

- application exposure, thus no qua ntitative occupational post

- application exposure and risk assessment has been performed.Page 21 of 25



### Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

Residential Non

- cancer Handler Algorithms

Dermal and Inhalation Handler Exposure Algor ithm Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given formulation

- application method combination, is estimated by multiplying the formulation

application method

- specific unit exposure by an estimate of the amoun t 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/ft 2 

### , lb ai/gal); and A = number of animals treated per day.

The daily doses are calculated using the following formula:

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),
E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/or inhalation), and BW = body weight (kg).

Residential Non

- cancer Post

- application Algorithms

Post

- application Dermal Exposure Algorithm The following method is used to calculate dermal exposures that are attributable to an adult or child contacting a treated companion pet:

E = TC * TR * ET

where:

E = exposure (mg/day); TC = transfer coefficient (cm 2 

### /hr);
TR = transferable residue (mg/cm 2 

### ); and
ET = exposure time (hours/day).Page 22 of 25



### where:

TR = transferable residue (mg/cm 2 

### ); AR = application rate or amount applied to anim al (mg);
F AR 

### = fraction of the application rate available as transferable residue; and SA = surface area of the pet (cm 2 

### ).

Absorbed dermal dose, normalized to body weight, is calculated as:

D = E * AF BW

where:
D = dose (mg/kg

- day);
E = exposure (mg/day); AF = absorption factor (dermal); and BW = body weight (kg).

Table A

- 1 : Treated Pets

– Inputs for Residential Post

- application Dermal Exposure Algorithm Notation Exposure Factor Units Point Estimates

AR Application rate (mg) Table 4.1

SA Surface Area of Animal

(cm 2 ) Small Cat, Dog Cat

– 1,500 Dog

– 3,000

Medium Cat, Dog Cat

– 2,500 Dog

– 7,000

Large Cat, Dog Cat

– 4,000 Dog

– 11,000

F AR Fraction of AR Available for Transfer 0.072% or 0.013%

TC Transfer Coefficient

–

Liquids (cm 2 /hr) Adult 5,200

Children 1 < 2 years old 1,400

Transfer Coefficient

– Solids (cm 2 /hr) Adult 140,000

Children 1 < 2 years old 38,000

ET Exposure Time

(hours per day) Adult 0.77

Children 1 < 2 years old 1.0

BW Body weight

(kg) Adult 80

Children 1 < 2 years old 11Page 23 of 25



### Post

- application Hand

- to

- Mouth Exposure Algorithm Exposure from hand

- to

- mouth activity is calculated as follows (based on algorithm utilized in SHEDS

- Multimedia):

E = [HR * (F

M 

### * SA H 

### ) * (ET * N_Replen) * (1

- (1

- SE) (Freq_HtM/N

- Replen) 

### )]

where:
E = exposure (mg/day);
HR = hand residue loading (mg/cm 2 

### ); SA H 

### = surface area of one child hand (cm 2 

### );
F M 

### = fraction hand surface area mouthed /event (fraction/event);
ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour); SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

HR = E * Fai hand s 

### 2 * SA H



### where:
HR = hand residue loading (mg/cm 2 

### );
E = dermal exposure (mg); Fai hands 

### = fraction of a.i. on hands compared to total residue from dermal transfer

coefficient study (unitless); and SA H 

### = surface area of one child hand (cm 2 

### ).

Oral dose, normalized to body weight, is calculated as:

D = E BW where:
D = dose (mg/kg

- day);
E = exposure (mg/day); and BW = body weight (kg).

Table A

- 2 : Treated Pets

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure Algorithm Notation Exposure Factor (units) Point Estimate(s)

Fai hands Fraction of a.i. on hands from transfer coefficient studies (unitless) Solid = 0.37 Liquid = 0.040

F M Fraction hand surface area mouthed /event (fraction/event) 0.13

N_Replen Replenishment intervals per hour 4Page 24 of 25

Table A

- 2 : Treated Pets

– Inputs for Residential Post

- application Hand

- to

- Mouth Exposure (intervals/hr)

ET Exposure time

(hours/day) Children 1 < 2 years old 1.0

SE Saliva extraction factor 0.48

Freq_HtM Hand

- to

- mouth events per hour (events/hr) Children 1 < 2 years old 20

SA H Typical surface area of one

child hand (cm 2 ) Children 1 < 2 years old 150

BW Body Weight (kg) Children 1 < 2 years old 11



### Occupational Non

- cancer Handler Algorithms

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

where:

E = e xposure (mg ai/day), UE = u nit e xposure (μ g ai/ lb ai), AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal ), and A = a rea treated or amount handled (e.g., A/day, gal/day)

.
The daily doses are calculated using the following formula:

where:

ADD = average daily dose a bsorbed in a given scenario (mg ai/ kg / day),
E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/or inhalation), and BW = body weight (kg)

.
Occupational Non

- cancer Post

- application Algorithms

Not applicable.Page 25 of 25



### Appendix B. Summary of Occupational and Residential Cancer Algorithms

After the development of the ADD values, the next step required to calculate carcinogenic risk estimates is to amortize these values over the anticipated lifetime, which results in the LADD. LADD values a re calculated using the following equation:

where :

LADD = absorbed dose over a lifetime (mg ai /kg/day), ADD = average daily dose absorbed in a given scenario (mg ai/kg/day)

, Days per Year of Exposure = annual frequency of an application by an individual (days/year), Years per Lifetime of Exposure = amount of a lifetime that an individual would be expected to use pesticides (years), and Lifetime Expectancy = average life expectancy of an individual (years).

C ancer risk estimate calculations a re completed by comparing the LADD values calculated above to the Q 1 

### * for the chemical . Cancer risk estimate s a re calculated using the following equation:

w here:



### Cancer Risk Estimate = probability of incidence of cancer cases over a lifet ime (unitless), Dermal LADD = absorbed dose from dermal exposure over a lifetime (mg ai /kg/day)

, Inhalation LADD = absorbed dose from inhalation exposure over a lifetime (mg ai /kg/day)

, and Q 1 

### * = quantitative dose response factor used for linear, low

- dose response cancer risk estimate calculations (mg/kg/day) - 1



### .