UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

Date: 

Subject: 

September 12, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Propoxur. Occupational 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 

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

TXRNo.:NA CAS No.: 114-26-1 

MRIDNo.: NA 

From: 

Through: 

To: 

Introduction 

40CFR:NA 

Shalu Shelat, Industrial Hygienist 1)\A ~ ~ "\Jl \'1.-\.rJ 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

Felecia Fort, Branch Chief ~- • C(, r ;/- 'f /J');/ /.3 

Risk 

Health 

Assessment 

Effects Division (7509P) 

Branch VI ~ ~ 

and 

Alexandra Lamay, ExpoSAC Designated Reviewer tf ~ AV 

Kelly 0' Rouke, ExpoSAC Designated Reviewer ~1'1.,4>~~ Exposure 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 

conducted as a response to a petition submitted by the Natural Resources Defense Council 

(NRDC) and posted in the public docket (EPA-HQ-OPP-2009-0207). The exposure estimates 

for propoxur use in pet collars had been previously addressed as part of the N-Methyl Carbamate 

Page I of25 
Cumulative Risk Assessment (2007) and most recently 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 that 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. Shelat, 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 Treated 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 of25 
Page 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 Recommendations from Residential Assessment .................................................. 6

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

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

4.0 Use 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............................. 25
Page 4 of 25

1.0 Executive Summary

Propoxur [o-isopropoxyphenyl 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. Exposures to propoxur can be expected to occur via the 

occupational and residential handler and post-application routes of exposure.

The toxicology database for propoxur is complete as described in 40 CFR, Part 158. As with 

other NMCs, propoxur inhibits acetylcholinesterase(AChE) by carbamylation of the serine 

hydroxyl group located in the active site of the enzyme. Toxicological characteristics 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 effect. EPA used the same benchmark dose (BMD) modeling approach that was 

developed for the OP cumulative risk assessment to assess the N-Methyl carbamates. 

A BMD analysis was conducted for both oral and inhalation endpoints. The acute oral Point of 

Departure (PoD) is based on a BMDL10 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 BMDL10 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 (Q1*) of 3.52 x 10-3(mg/kg/day)-1. However, this linear lowdose 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 increased 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 

inhibition. 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 dataderived 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 not 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 considered 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) for 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 postapplication 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, respectively. Non-cancer risk estimates for the postapplication 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 Board. 

Descriptions of data sources, as well as guidance on their use, can be found at the Agency 

website2. 

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.html
Page 6 of 25

2.1 Summary of Risk Estimates

2.2 Label Recommendations from Occupational Assessment 

HED has no label recommendations based on the occupational assessment.

2.3 Label Recommendations from Residential Assessment

HED has no 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 toxicity category II by oral route, and category III by dermal and inhalation 

routes. Propoxur 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] LD50 (M) = 94 mg/kg

LD50 (F) = 68 mg/kg II

870.1200 Acute dermal [rabbit] LD50: >2000 mg/kg III

870.1300 Acute inhalation [rat] LC50 >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 BMDL10 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 BMDL10 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 (Q1*) 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 NonOccupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental Oral 

Acute

BMDL10 = 

0.0285

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD =

aPAD

=0.000285 

mg/kg/day

Acute comparative cholinesterase assay 

(MRID 48784802, 48784803 BMD10 = 

0.0427 mg/kg/day

BMDL10 = 0.0285 mg/kg/day based on 

RBC ChE inhibition in male and female 

PND11 pups (combined)

Inhalation 

Acute

BMDL10

F= 0.0076 

mg/L

Residential

HEC =

1.67 

mg/kg;

7 mg/m3;

0.007 mg/L

UFA = 3X

UFH = 10X

FQPA SF= 11X

Residential 

(children) 

LOC= 330

Residential 

(adult)

LOC= 30

Chronic inhalation study - Rats (MRID 

42648001; 40836402)

BMD10 F= 0.0095 mg/L

BMDL10 F= 0.0076 mg/L based on ChE 

in the brain

BMD10 M= 0.016 mg/L

BMDL10 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 carcinomas in high- dose females 

(MRID 00142725). The Q1* 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. UFA = extrapolation from animal to human (interspecies). UFH = 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. 

Absorption
Page 8 of 25

A dermal absorption factor of 19.6% was used for the exposure assessment (MRID 43736616). 

Absorption by the inhalation route is considered to be equivalent to the estimated toxicity 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 Profile 

There are a number of currently 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 residences. Propoxur is also registered as 

granular and impregnated formulations (i.e., pet collars and bait 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 2889
Page 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. Residential uses have 

been assessed in this document to reflect updates to HED’s 2012 Residential SOPs3along 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 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: 

Applying propoxur impregnated pet collars to companion animals

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.

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.gov/pesticides/science/residential-exposure-sop.html
Page 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 SOPs4.

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 Per Year of Exposure: 

Residential handler exposure is expected to occur several times per year. The length of time 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 it 

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 Per Lifetime of Exposure:

It is assumed that residential handlers would be exposed for 50 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. 

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 SOPs5.

Combining Exposures/Risk Estimates:

Dermal and inhalation risk estimates 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 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 not 

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.html
Page 11 of 25

Residential Handler Cancer Exposure and Risk Estimate Equations

A Q1

* 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 exposure and risk assessment was 

performed because dermal exposure does contribute to the overall cancer risk for propoxur. 

Dermal exposures were calculated based on the use pattern and algorithms as provided in the 

2012 Residential SOPs. The calculated dermal 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 Q1* that has been calculated for propoxur based on dose response data in the appropriate 

toxicology study (Q1* = 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 3E-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 Estimate2

Dermal1 Q1* = 3.52 x10-3

Wellmark International

Small Dog Collar 1.8E-05 6E-08

Medium Dog Collar 3.1E-05 1E-07

Large Dog Collar 3.1E-05 1E-07

Small Cat Collar 9.5E-06 3E-08

Medium Cat Collar 9.5E-06 3E-08

Large Cat Collar 9.5E-06 3E-08

Sergeant’s Pet Care Products, Inc

Small Dog Collar 1.6E-05 6E-08

Medium Dog Collar 2.3E-05 8E-08

Large Dog Collar 2.6E-05 9E-08

Small Cat Collar 1.1E-05 4E-08

Medium Cat Collar 1.3E-05 5E-08

Large Cat Collar 1.3E-05 5E-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) * Q1

*

, where Q1

*

= 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 old
Page 12 of 25

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs6. 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 served as the basis for completing the residential 

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

SOPs6. 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 was the most appropriate for the noncancer 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% was 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 Per Year of Exposure: 

Residential post-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 up 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 exposure for 180 days and 365 days per year to 

represent both partial and full year exposure to companion animal collars.

Years Per Lifetime of Exposure:

It is assumed that residential post-application exposure would occur for 50 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. 

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 SOPs6.

 

6 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 13 of 25

Combining Exposure and Risk Estimates

Dermal and incidental oral risk estimates 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 years 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 concern (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 

Rate1

(mg ai/collar)

Dose 

(mg/kg/day)2 MOEs3

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 labels 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 Q1* that has been calculated for propoxur based on dose response data 

in the appropriate toxicology study (Q1* = 3.52x10-3(mg/kg/day)-1). The algorithms used to 

estimate the LADD and cancer risk for residential post-application exposure 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 Estimates
Page 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 

Estimate2

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 × Q1

*

, where Q1

*

= 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 

Estimate2

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 × Q1

*

, where Q1

*

= 3.52x10-3(mg/kg/day)-1

5.3 Residential Risk Estimates for Use in Aggregate Assessment

Tables 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-application 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 exposure to small cats 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 MOE4

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-04 N/A N/A 6.9 E-04 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 scenarios 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/Inhalation MOE) + (1/Incidental oral MOE), if 

applicable. 
Page 17 of 25

5.4 Spray Drift

This assessment is conducted for the propoxur end use product formulated as an impregnated pet 

collar and is unlikely to result in spray drift.

5.5 Residential Bystander Post-Application Inhalation Exposure

A quantitative residential post-application inhalation exposure assessment was not performed 

because the inhalation route of exposure is considered negligible for the companion pet collar 

scenario and would not 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. 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: 

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 these 

data are proprietary, and subject to the data protection provisions of FIFRA. 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 
Page 18 of 25

Reference Table7”, 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 website8.

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, 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 propoxur impregnated collars, it is reasonable to believe 

that groomers or veterinary professionals may apply collars to companion animals throughout the 

year. Although the exposure duration for pet collars can be considered longer-term, propoxur is 

part of the N-methyl carbamate chemical class. Toxicological characteristics of propoxur, like 

the other 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 daily 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 cancer 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 collars handled over the course of one

year.

Years per Lifetime of Exposure: It is assumed that handlers would be exposed 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.html
Page 19 of 25

Dermal and inhalation risk estimates 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 Handler Non-Cancer Exposure and Risk Estimates

A dermal and inhalation non-cancer assessment was not completed based on the information 

provided above.

Occupational Handler Cancer Exposure and Risk Equations

A Q1

* 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 exposure and risk assessment was 

performed because dermal exposure does contribute to the overall cancer risk for propoxur. The 

calculated dermal 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 Q1* that 

has been calculated for propoxur based on dose response data in the appropriate toxicology study 

(Q1* = 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 estimates range from 4 E-07 to 1E-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 Estimate2

Dermal1 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-07
Page 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 × Q1

*

, where Q1

*

= 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 referred to as reentry exposure). In the case of the 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 quantitative 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 Algorithm

Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given 

formulation-application method combination, is estimated by multiplying the formulationapplication 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 = 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 = exposure (mg ai/day),

AF = absorption factor (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 (cm2/hr);

TR = transferable residue (mg/cm2); and

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

where:

TR = transferable residue (mg/cm2);

AR = application rate or amount applied to animal (mg);

FAR = fraction of the application rate available as transferable residue; and

SA = surface area of the pet (cm2).

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 

(cm2)

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

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

TC

Transfer Coefficient –

Liquids 

(cm2/hr)

Adult 5,200

Children 1 < 2 years old 1,400

Transfer Coefficient –

Solids

(cm2/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 11
Page 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 * (FM * SAH ) * (ET * N_Replen) * (1- (1- SE) (Freq_HtM/N-Replen))]

where:

E = exposure (mg/day);

HR = hand residue loading (mg/cm2);

SAH = surface area of one child hand (cm2);

FM = 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 * Faihands

 2 * SAH

where:

HR = hand residue loading (mg/cm2);

E = dermal exposure (mg);

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

coefficient study (unitless); and

SAH = surface area of one child hand (cm2).

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

FM

Fraction hand surface area mouthed /event 

(fraction/event) 0.13

N_Replen Replenishment intervals per hour 4
Page 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

SAH

Typical surface area of one 

child hand

(cm2)

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 = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

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

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

AF = absorption factor (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 are 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).

Cancer risk estimate calculations are completed by comparing the LADD values calculated 

above to the Q1* for the chemical. Cancer risk estimates are calculated using the following 

equation:

where:

Cancer Risk Estimate = probability of incidence of cancer cases over a lifetime (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

Q1* = quantitative dose response factor used for linear, low-dose response 

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