UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: November 5, 2014 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Residential Exposure Assessment in Response to the Natural Resources 

Defense Council Petition to Cancel All Pet Uses for Tetrachlorvinphos 

PC Code: 083701 

Petition No.: NA 

Risk Assessment Type: Single Chemical, 

Residential Exposure Assessment 

TXRNo.: NA 

MRID No.: 45485501,45519601,48589901 

DP Barcode: D420283 

Registration Nos.: NA 

Regulatory Action: Petition Response 

Case No.: NA 

CAS No.: 22248-79-9 

FROM: Wade Britton, MPH, Industrial Hygienist /UJj Risk Assessment Branch V (RABV) t/{ 

Health Effects Division (HED; 7509P) 

Office of Pesticide Programs ~ I ~ 

THROUGH: Michael Metzger, Chief D 0 /( 

RABV and RABVIIJHED (75 . And n . Kristin Rury, Biologist \(, :l.-.JI'l-,....,... ---..~. 

Nancy J. Tsaur, Chemist \1 J 

Exposure Science Advisory tlo 

TO: Neil Anderson, Branch Chief 

Kelly Ballard, Chemical Review Manager 

Risk Management and Implementation Branch I (RMIBI) 

Pesticide Re-evaluation Division (PRD; 7508P) 

Office of Pesticide Programs 

The purpose of this document is to provide a residential exposure assessment for all pet uses of 

the active ingredient, tetrachlorvinphos (TCVP). On April 23, 2009, the Natural Resources 

Defense Council (NRDC) petitioned the Agency to cancel all pet uses of TCVP. This 

assessment was conducted as a response to NRDC's petition and characterizes the potential 

risks associated with the use of TCVP pet products. An earlier exposure assessment was also 

Page 1 of 45 
Page 2 of 45

conducted1in response to the petition that identified no human health risks of concern from

residential use of TCVP pet products. This current exposure assessment makes use of the 2012 

Standard Operating Procedures for Residential Pesticide Exposure Assessment (2012 

Residential SOPs), the Agency’s most current guidance for the assessment of human health 

exposures from residential pesticide usage. This assessment also incorporates changes that have 

occurred since the prior assessment including the following: updates to toxicological points of 

departure (PoDs) and uncertainty factors (UFs); voluntary product cancellations; label 

amendments; a re-evaluation of previously submitted exposure data; and use of a recently 

submitted pet collar pet residue transfer study. This current exposure assessment supersedes the 

prior exposure assessment and is posted to the public docket (EPA-HQ-OPP-2009-0356). 

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 2012 Residential SOPs (Treated Pets SOP), and a propoxur collar pet residue 

transfer study (MRID 48589901). A TCVP dust/powder applicator exposure study (MRID 

45519601), and TCVP dust and pump spray study (MRID 45485501) were also used. Both 

TCVP studies were included as a part of the 2012 Residential SOPs. 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) May 8, 2014.

 

1

J. Dawson. Tetrachlorovinphos: Summary of Pet Collar Risk Estimates. 2/22/10. D346880. 
Page 3 of 45

Table of Contents

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

2.0 Risk Assessment Conclusions and Recommendations........................................................ 7

2.1 Summary of Risk Estimates............................................................................................. 7

2.2 Label Recommendations from Residential Assessment .................................................. 7

2.3 Data Deficiencies and Requirements ............................................................................... 7

3.0 Hazard Characterization and Dose-Response Assessment.................................................. 7

4.0 Use Profile ......................................................................................................................... 12

5.0 Residential Exposure and Risk Estimates.......................................................................... 14

5.1 Residential Handler Exposures ...................................................................................... 15

5.2 Residential Post-application Exposure/Risk Estimates.................................................. 22

5.3 Residential Risk Characterization .................................................................................. 31

5.4 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 37

5.5 Spray Drift...................................................................................................................... 38

5.6 Residential Bystander Post-Application Inhalation Exposure ....................................... 38

Appendix A: Algorithms Used to Calculate Residential Non-Cancer and Cancer Risk Estimates

....................................................................................................................................................... 39
Page 4 of 45

1.0 Executive Summary

Tetrachlorvinphos (TCVP) is a member of the organophosphate (OP) class of pesticides. TCVP

is used as a direct animal treatment to livestock and their premises, outdoors in recreational 

areas, and as a flea treatment on cats and dogs. Currently registered TCVP pet products include 

collar, dust/powder, and pump and trigger spray formulations. This assessment is intended to 

address only those issues raised in the 2009 NRDC petition regarding the potential exposures 

resulting from residential TCVP pet product usage. Residential exposures are anticipated for 

adults who apply TCVP products to pets and for adults and children contacting previously 

treated pets. 

Hazard

Like other OPs, the initiating event in the adverse outcome pathway (AOP)/mode of action 

(MOA) for TCVP involves inhibition of the enzyme acetylcholinesterase (AChE) via 

phosphorylation of the serine residue at the active site of the enzyme. This inhibition leads to 

accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral 

nervous system. For TCVP, AChE inhibition is the most sensitive endpoint in the toxicology 

database in multiple species, durations, lifestages, and routes. 

The toxicology database for TCVP is complete. TCVP has low acute (lethality) toxicity by the 

oral, dermal, and inhalation routes of exposure. It is a slight dermal irritant, a moderate eye 

irritant, and a dermal sensitizer. TCVP is classified as a possible human (Group C) carcinogen 

based on statistically significant increases in combined hepatocellular adenoma/carcinomas in 

mice, and suggestive evidence of thyroid c-cell adenomas and adrenal pheochromocytomas in 

rats. The mutagenicity database for TCVP suggests that this chemical was not mutagenic in 

both the gene mutation assay and primary rat hepatocyte unscheduled DNA synthesis assay.

However, this chemical was positive for inducing chromosomal aberrations in Chinese hamster 

ovary cells in the absence of metabolic activation, but was negative in the presence of metabolic 

activation. Immunotoxicity was not observed at dose levels that exceed the limit dose.

Developmental toxicity was observed in the rabbit developmental toxicity study, as evidenced by 

an increase in abortions and early resorptions, with an increase in post-implantation loss and a 

decrease in live fetuses at the same dose level where mortality, abortions, and red vaginal fluid 

were observed in the maternal rabbit. Developmental toxicity was not observed in the rat 

developmental toxicity study. No reproductive toxicity was observed in the 2-generation 

reproductive study in rats, but increased adrenal weights were observed in the parental rats. 

Transient clinical signs characteristic of cholinergic toxicity were observed in the acute and 

subchronic neurotoxicity studies in rats, but no clinical signs were observed in the maternal rats 

or in the offspring in the developmental neurotoxicity study. However, cholinesterase activity 

was not measured in any of these neurotoxicity studies. There are comparative cholinesterase 

studies as well as subchronic and chronic oral toxicity studies on TCVP that provide 

cholinesterase dose response data across multiple lifestages, durations, and routes of exposure 

for both red blood cell (RBC) and brain cholinesterase inhibition. No clinical signs 

characteristic of cholinergic toxicity were observed in any of these assays. Many of these 
Page 5 of 45

studies have been evaluated using benchmark dose modeling techniques.

Endpoints and Uncertainty Factors for Risk Assessment

Like other OPs, TCVP exhibits a phenomenon known as steady state AChE inhibition. After 

repeated dosing at the same dose level, the degree of inhibition comes into equilibrium with the 

production of new, uninhibited enzyme. At this point, the amount of AChE inhibition at a given 

dose remains consistent across duration. In general, OPs reach steady state within 2-3 weeks but 

this can vary among OPs. Based on the robust dataset from the OP cumulative risk assessment 

across the OPs, exposure assessments of 21 days and longer will be conducted for all routes of 

exposure; i.e., oral, dermal, and inhalation, for all single chemical OP assessments. Given this, 

the 21-day and longer exposure assessment is scientifically supportable and also provides 

consistency with the OP cumulative risk assessment and across the OP registration review risk 

assessments. 

For the dermal and incidental oral risk assessments, a steady state PoD was selected, a

benchmark dose lower confidence limit for 10% RBC AChE inhibition (BMDL10) of 8.01 

mg/kg/day, from the subchronic oral toxicity study in rats based on the endpoint (RBC AChE 

inhibition). The RBC cholinesterase data from this study were evaluated using benchmark dose 

modeling (BMD) techniques to be consistent with the current methods being used for the OPs. 

Since an oral study was selected, a dermal absorption factor (DAF) of 9.57% should be used in 

the route-to-route extrapolation. The DAF is based on the results of a dermal penetration study in 

rats. 

For the inhalation risk assessment, a steady state PoD was selected, a BMDL10 of 0.02 mg/L/day, 

based on a route-specific endpoint from the subchronic inhalation toxicity study in rats. Using 

the Agency’s Reference concentration (RfC) methodology, a human equivalent concentration 

(HEC) was calculated. The HEC is 0.058 mg/L/day, and the Human Equivalent Dose is 1.65 

mg/kg/day. 

TCVP is classified as a Group C possible human carcinogen by the Agency with a linear lowdose approach for quantification of risk using the oral slope factor (Q1*) of 1.83 x 10-3

(mg/kg/day)-1.

The Food Quality Protection Act (FQPA) safety factor (SF) was reduced to 1X since there is no 

evidence of sensitivity of the young animal compared to the adult and there are no data gaps. A 

total UF of 100X is appropriate for dermal and incidental oral routes of exposure (10X for 

interspecies extrapolation, 10X for intraspecies variation, and 1X FQPA SF). For the inhalation 

route of exposure, a total SF of 30X (3X for interspecies extrapolation, 10X for intraspecies 

variation, and 1X FQPA SF) is appropriate. The interspecies extrapolation is reduced from 10X 

to 3X because the reference concentration RfC methodology for inhalation is used to determine 

an HEC and takes into consideration the pharmacokinetic differences between animals and 

humans.
Page 6 of 45

Residential Exposure and Risk

Residential exposures are anticipated from the use of TCVP pet products. Residential TCVP 

handler and post-application exposures are anticipated to be short- (1 to 30 days) to 

intermediate-term (1 to 6 months) in duration. However, because of the steady state AChE 

inhibition exhibited by the OPs, steady state exposures (21 days and longer) were assessed and 

presented for residential exposures to TCVP pet products. 

As mentioned previously, this residential exposure assessment supersedes the 2010 assessment 

of exposures from TCVP pet products. It reflects the use of the 2012 Standard Operating 

Procedures for Residential Pesticide Exposure Assessment (2012 Residential SOPs), the 

Agency’s most current guidance for the assessment of human health exposures from residential 

pesticide usage. This assessment also incorporates the following changes: 

 the assumption of steady state exposures for TCVP exposure assessment; 

 updated PoDs following reevaluation of the TCVP toxicity database using the BMD 

techniques consistent with the methods currently used for other OPs;

 reduction of the total UF for inhalation exposures from 100X to 30X due to use of the 

Agency’s RfC/HEC methodology; 

 voluntary cancellation of TCVP trigger pump spray pet products (EPA Reg. Nos. 2596-

122, 2596-123, and 2596-136); 

 data submitted by the product registrant Hartz Mountain Corporation regarding the 

amount of TCVP dispensed per stroke of a pump or trigger spray pet product; 

 a master label amendment change for pump and trigger spray products (EPA Reg. No. 

2596-140) that defines the number of strokes per pet based on animal size; 

 the re-evaluation of a previously submitted and reviewed pet residue transfer study for 

TCVP dust/powder and pump spray formulations; and

 the use of a pet residue transfer study data specific to collar formulations. 

Residential handler (adults) combined steady state (dermal and inhalation) exposures are not of 

concern to the Agency (i.e., all aggregate risk indexes (ARIs) are ≥ 1) from application of any 

registered TCVP pet product. The ARI approach was required to combine the dermal and 

inhalation routes of exposure because of the different levels of concern (LOCs).

Residential post-application steady state adult dermal (only) exposure and children 1 to < 2 

years old combined (dermal and incidental oral exposures) are not of concern to the Agency 

(i.e, all MOEs are ≥ 100) for all TCVP pet products assessed. The combined MOE approach 

was used because the dermal and incidental oral routes of exposure have the same LOC.

Estimated residential handler cancer risk estimates range from 10-9to 10-7, and residential postapplication cancer risk estimates range from 10-8

to 10-6. 

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 2012 

Residential SOPs (Treated Pets SOP), as well as a TCVP dust/powder applicator exposure study 
Page 7 of 45

(MRID 45519601), and TCVP dust and pump spray study (MRID 45485501) and propoxur 

collar pet residue transfer studies (MRID 48589901) are (1) subject to ethics review pursuant to 

40 CFR Part 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 website.

2

 

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

All residential handler and post-application TCVP pet product non-cancer exposure scenarios 

assessed resulted in risk estimates that are not of concern to the Agency. For adults, estimated 

residential handler cancer risk estimates range from 10-9to 10-7, and residential post-application 

cancer risk estimates range from 10-8to 10-6. 

2.2 Label Recommendations from Residential Assessment

As currently written, label language for the trigger spray products (EPA Reg. No. 2596-125 and 

2596-126) states that “more spray may be needed for longhaired [cats/dogs].” HED recommends 

that this language should be removed from the product labels as it could potentially allow for 

more than the prescribed number of strokes from a trigger spray to be applied to an animal. 

2.3 Data Deficiencies and Requirements

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

3.0 Hazard Characterization and Dose-Response Assessment

TCVP is a member of the organophosphate class of pesticides. Like other OPs, the initiating 

event in the adverse outcome pathway/mode of action (AOP/ MOA) for TCVP involves 

inhibition of the enzyme AChE via phosphorylation of the serine residue at the active site of the 

enzyme. This inhibition leads to accumulation of acetylcholine and ultimately to neurotoxicity 

in the central and/or peripheral nervous system (see Figure 1). For TCVP, AChE inhibition is 

the most sensitive endpoint in the toxicology database in multiple species, durations, lifestages, 

and routes. AChE inhibition is the focus of this hazard characterization; the availability of 

reliable AChE inhibition dose response data is one of the key determinants in evaluating this 

toxicology database. 

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 8 of 45

Figure 1. Adverse outcome pathway for OPs

In subchronic and chronic toxicity/carcinogenicity studies in rats, effects observed in addition to 

cholinesterase inhibition were microscopic lesions in the liver, kidney, thyroid, and adrenal

gland. In the carcinogenicity study in mice, increases were observed in the hepatocellular 

adenomas and carcinomas in males. In the chronic oral toxicity study in dogs, cholinesterase 

inhibition and increased liver and kidney weights were observed. The mutagenicity database 

suggests that TCVP was not mutagenic in both gene mutation assays and the primary rat 

hepatocyte unscheduled DNA synthesis assay. However, TCVP was positive for inducing 

chromosomal aberrations in Chinese hamster ovary cells in the absence of metabolic activation 

and was negative in the presence of metabolic activation. TCVP is classified as a possible 

human carcinogen. Immunotoxicity was not observed at dose levels that exceed the limit dose.

Developmental toxicity was observed in the rabbit developmental toxicity study, as evidenced by 

an increase in abortions and early resorptions, with an increase in post-implantation loss and a 

decrease in live fetuses at the same dose level where mortality, abortions, and red vaginal fluid 

were observed in the maternal rabbit. Developmental toxicity was not observed in the rat 

developmental toxicity study. No reproductive toxicity was observed in the 2-generation 

reproductive study in rats, but increased adrenal weights were observed in the parental rats. 

Transient clinical signs characteristic of cholinergic toxicity were observed in the acute and 

subchronic neurotoxicity studies in rats, but no clinical signs were observed in the maternal rats 

or in the offspring in the developmental neurotoxicity study. However, cholinesterase activity 

was not measured in any of these neurotoxicity studies. There are comparative cholinesterase 

studies as well as subchronic and chronic oral toxicity studies on TCVP that provide 

cholinesterase dose response data across multiple lifestages, durations, and routes of exposure for 

both RBC and brain cholinesterase inhibition. No clinical signs characteristic of cholinergic 

toxicity were observed in any of these assays. Many of these studies have been evaluated using 

benchmark dose modeling techniques. For all three components of the comparative 

cholinesterase assays (i.e, acute, repeated, and gestational) for TCVP, the dose response data are 

not robust enough for BMD analysis due to high variability in the AChE data. However, these 

studies do support a conclusion that there is no lifestage sensitivity observed for TCVP. Further 

support comes from time course study in pups and adults which provides high quality data and 

shows no age-dependent sensitivity. 

Acute Toxicity

TCVP has low acute toxicity by the oral, dermal, and inhalation routes of exposure. It is a slight 

dermal irritant, a moderate eye irritant, and a dermal sensitizer. 

Target 

Tissue Dose

Phosphorylation 

of the active site 

of AChE

Neurotoxicity

Accumulation 

of 

acetylcholine
Page 9 of 45

Table 3.0. Acute Toxicity of Tetrachlorvinphos Technical

Guideline 

No.

Study Type MRID 

No.

Results

Toxicity 

Category

870.1100 Acute Oral – Rat 41222504

LD50 =

1480 mg/kg (M)

465-965 mg/kg (F) III

870.1200 Acute Dermal – Rabbit 41222505 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation - Rat 00138933 LC50 > 3.61mg/L IV

870.2400 Acute Eye Irritation - Rabbit 41222506 moderate III

870.2500 Acute Dermal Irritation - Rabbit 41222507 slight IV

870.2600 Skin Sensitization - Guinea Pig 41377902

42981001 sensitizer N/A

870.6100 Acute Delayed Neurotoxicity 41905901

No clinical signs of 

neurotoxicity observed

(NTE not measured)

N/A

Toxicological PoDs Used for Risk Assessment 

Like other OPs, TCVP exhibits a phenomenon known as steady state AChE inhibition. After 

repeated dosing at the same dose level, the degree of inhibition comes into equilibrium with the 

production of new, uninhibited enzyme. At this point, the amount of AChE inhibition at a given 

dose remains consistent across duration. In general, OPs reach steady state within 2-3 weeks, but 

this can vary among OPs. Based on the robust dataset from the OP cumulative risk assessment 

across the OPs, exposure assessments of 21 days and longer will be conducted for all routes of 

exposure; i.e., oral, dermal, and inhalation, for all single chemical OP assessments. Given this, 

the 21-day and longer exposure assessment is scientifically supportable and also provides 

consistency with the OP cumulative risk assessment and across the OP registration review risk 

assessments.

TCVP shows a shallow dose-response curve for cholinesterase inhibition; in other words, large 

increases in administered dose result in only small changes in AChE inhibition. This shallow 

dose response leads to variability in the AChE data and a relatively broad range of 

BMD10/BMDL10 values from 6.8 to 61.6 mg/kg/day/3.6 to 26.3 mg/kg/day. Moreover, when 

evaluating the data across the database, the magnitude of AChE inhibition varies across different 

studies at comparable dose levels. For example, in the chronic rat toxicity study, increasing the 

dose from 5.9 mg/kg/day to 62.7 mg/kg/day only leads to changes in female RBC AChE 

inhibition of 10% or less. In the same study at a dose of 125 mg/kg/day, females displayed 17%-

25% RBC cholinesterase inhibition, whereas males displayed no RBC cholinesterase inhibition 

at 88 mg/kg/day. Similarly, in the gestational study, pregnant dams did not exhibit any inhibition 

up to a dose of 75 mg/kg/day, whereas in the 21-day subchronic study, female rats showed 

approximately 40% RBC AChE inhibition at a dose of 50 mg/kg/day. 
Page 10 of 45

Consistent with risk assessments for other AChE-inhibiting compounds, OPP has conducted a

BMD analysis using a benchmark response (BMR) level of 10%, and has thus calculated BMD10

and BMDL10 values. The BMD10 is the estimated dose where ChE is inhibited by 10% 

compared to background. The BMDL10 is the lower confidence bound on the BMD10. As a 

matter of science policy, the agency uses the BMDL, not the BMD, for use as the PoD (USEPA, 

20123). All BMD/BMDL modeling was completed using USEPA BMD Software, version 2.2; 

an exponential model was used to fit the data, with the assumption of constant variance across 

each dataset. A summary of OPP’s cholinesterase (ChE) policy and use of BMD modeling, and 

the results of the TCVP BMD analyses, can be found in Appendices B and C of this document, 

respectively. The technical details of the analysis can be found in a separate BMD 

memorandum.

4

BMD assessment of the 90-day subchronic oral study provides a BMD10 of 10.4 mg/kg/day and a 

BMDL10 of 8.01 mg/kg/day. The previous risk assessment used the no-observed-adverse-effect 

level (NOAEL) of 6.7 mg/kg/day from this same study. This BMDL10 of 8.01 mg/kg/day was 

selected for the dermal and incidental oral risk assessments. This study was selected because it 

has the most robust dose-response data for deriving PoDs. There are BMDL10 values in Table 

C.1 in Appendix C that provide lower BMDL10 values (comparative cholinesterase assays), but 

due to high variability in the AChE data and the fact that no cholinesterase inhibition was 

observed at dose levels equal to and greater than these lower BMD10/BMDL10 values, they were 

not considered appropriate for deriving PoDs. 

For the inhalation risk assessment, a steady state PoD was selected, BMDL10 of 0.02 mg/L/day, 

based on a route-specific endpoint from the subchronic inhalation toxicity study in rats. Using 

the Agency’s Reference concentration (RfC) methodology, a human equivalent concentration 

(HEC) was calculated. The HEC is 0.058 mg/L/day, and the Human Equivalent Dose is 1.653 

mg/kg/day. 

TCVP is classified as a Group C possible human carcinogen by the Agency with a linear lowdose approach for quantification of risk using the oral slope factor (Q1*) of 1.83 x 10-3

(mg/kg/day)-1.

The Food Quality Protection Act (FQPA) safety factor (SF) was reduced to 1X since there is no 

evidence of sensitivity of the young animal compared to the adult and there are no data gaps. A 

total uncertainty factor (UF) of 100X is appropriate for dermal and incidental oral routes of 

exposure (10X for interspecies extrapolation, 10X for intraspecies variation, and 1X FQPA SF). 

For the inhalation route of exposure, a total SF of 30X (3X for interspecies extrapolation, 10X 

for intraspecies variation, and 1X FQPA SF) is appropriate. The interspecies extrapolation is 

reduced from 10X to 3X because the reference concentration RfC methodology for inhalation is 

used to determine an HEC and takes into consideration the pharmacokinetic differences 

between animals and humans.

 

3 USEPA Benchmark Dose Guidance: http://www.epa.gov/raf/publications/pdfs/benchmark_dose_guidance.pdf

4

J. Bever. Tetrachlorvinphos: Benchmark Dose Analysis of Subchronic and Chronic Studies to Support Derivation 

of Points of Departure. 5/20/2014. TXR # 0056970. D420286. 
Page 11 of 45

Absorption

Because an oral study was selected for dermal exposure assessment, a dermal absorption factor 

(DAF) of 9.57% should be used in the route-to-route extrapolation. The DAF is based on the 

results of a dermal penetration study in rats. Since the inhalation PoD was based on a routespecific toxicity study, no absorption factor was necessary to estimate exposure.

Body Weight

The standard body weight for the general adult population, 80 kg, was used for all exposure 

scenarios covered in this risk assessment since the endpoints selected were not based on 

developmental and/or fetal effects. A body weight of 11kg was assumed for children 1 to < 2 

years old. 

Table 3.1. Summary of Toxicological Doses and Endpoints for TCVP for Use in Residential 

Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental 

Oral

(steady state)

NOAEL= 6.7 

mg/kg/day

BMDL10 = 

8.0 mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

1x

Residential LOC 

for MOE = 100

Subchronic Oral Toxicity Study – Rat

LOAEL was 142 mg/kg/day based on 

RBC ChE inhibition

BMD10 = 10.49 mg/kg/day, based on 

female RBC ChE inhibition

Dermal 

(steady state)

NOAEL= 6.7 

mg/kg/day

BMDL10 = 

8.0 mg/kg/day

Dermal 

Absorption

= 9.57% a

UFA= 10x

UFH=10x

FQPA SF = 

1x

Residential LOC 

for MOE = 100

Subchronic Oral Toxicity Study – Rat

LOAEL was 142 mg/kg/day based on 

RBC ChE inhibition

BMD10 = 10.49 mg/kg/day, based on 

female RBC ChE inhibition

Inhalation 

(steady state)

NOAEL= 

0.05

mg/L/day

BMDL10=0.02 

mg/L/day 

(males)

HEC=0.058 

mg/L/dayb

HED=1.653c 

mg/kg/day

UFA= 3x

UFH=10x

FQPA SF = 

1x

Residential LOC 

for MOE = 30

Subchronic Inhalation Toxicity Study -

Rat

LOAEL = 0.5 mg/L, based on RBC ChE 

inhibition in males and females

BMD10 = 0.12 mg/L/day, based on RBC 

ChE inhibition in both sexes

Cancer 

(oral, dermal, 

inhalation)

Classification: A possible human (Group C) carcinogen. Q1* = 1.83 x 10-3

(mg/kg/day)-1

1 Explanation of Abbreviations: 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 
Page 12 of 45

relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among 

members of the human population (intraspecies); MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

a = Since an oral NOAEL was selected, a dermal absorption factor of 9.57% should be used in route-to-route extrapolation 

(MRID 41862401/ MRID 42111501).

b Human Equivalent Concentration (HEC) = 0.058 mg/L; PoD (BMDL10 0.022867 mg/L) x (RDDR 2.525)

c Human Equivalent Dose (HED) = 1.65 mg/kg/day.

4.0 Use Profile 

TCVP is used as a direct animal treatment to livestock and their premises, outdoors in 

recreational areas, and as a flea treatment on cats and dogs. Table 4.0 below presents the current 

residential pet uses of TCVP that include collar, dust/powder, and pump and trigger spray 

formulations. 

Table 4.0. Summary of Registered TCVP Pet Products

EPA Reg. 

No. Use Site Application Rate Use Restrictions

Collars

2596-49 Cats

1,650 mg ai 

11.3 gram collar 

(14.6% ai)

Do not use in kittens under 12 weeks of age. 

Place the collar around the cat’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 3 months, every 2 months for severe 

infestation.

2596-50

Dogs

2,770 mg ai

19 gram collar 

(14.6 % ai)

4,670 mg ai

32 gram collar

(14.6% ai)

Do not use on puppies less than 6 weeks of age. 

Place the collar around the dog’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 3 months, every 2 months for severe 

infestation.

2596-62

Do not use on puppies less than 12 weeks of age. 

Place the collar around the dog’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 5 months, every 4 months for severe 

infestation.

2596-63 Cats

2,190 mg ai

15 gram collar 

(14.6% ai)

2,480 mg ai

17 gram collar

(14.6% ai)

Do not use on kittens less than 12 weeks of age. 

Place the collar around the cat’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 5 months, every 4 months for severe 

infestation.

2596-83 Cats

1,750 mg ai

12 gram collar

(14.6% ai)

3,650 mg ai

25 gram collar 

(14.6% ai)

Do not use on kittens less than 12 weeks of age. 

Place the collar around the cat’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 7 months, every 5 months for severe 

infestation.
Page 13 of 45

Table 4.0. Summary of Registered TCVP Pet Products

EPA Reg. 

No. Use Site Application Rate Use Restrictions

2596-84 Dogs

2,770 mg ai

19 gram collar

(14.6% ai)

4,670 mg ai

32 gram collar

(14.6% ai)

Do not use on puppies under 6 weeks of age. 

Place the collar around the dog’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 7 months, every 5 months for severe 

infestation.

2596-139 Cats/

Dogs

1,460 mg ai

10 gram collar

(14.6% ai)

7,300 mg ai

50 gram collar

(14.6% ai)

Do not use on puppies under 6 weeks old/ kittens under 12 weeks 

old. 

Place the collar around the cat’s/dog’s neck, adjust for proper fit, 

and buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 7 months, or more frequently for severe 

infestation.

11556-164 Dogs

3,290 mg ai

24 gram collar

(13.7% ai)

Do not use on puppies under 6 weeks. 

Place the collar around the dog’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 5 months, every 4 months for severe 

infestation.

11556-165 Cats

2,060 mg ai

15 gram collar

(13.7% ai)

Do not use on kittens less than 12 weeks of age. 

Place the collar around the cat’s neck, adjust for proper fit, and 

buckle in place. 

Leave 2 or 3 inches on the collar for extra adjustment and cut off 

and dispose of the extra length. 

Replace the collar every 5 months, every 4 months for severe 

infestation.

Dusts/Powders

2596-78 Cats

280 mg ai (3.3% ai)

0.30 ounce per small cat

470 mg ai (3.3% ai) 

0.5 ounce per large cat

Not for use on kittens less than 12 weeks of age. 

Dust entire cat beginning at head and working back. 

Use approximately 1/3 ounce of powder for a small cat or 1⁄2 ounce 

for a large cat.

Repeat at weekly intervals if necessary. 

2596-79 Dogs

470 mg ai (3.3% ai)

1⁄2 ounce per small dog

940 mg ai 

1 ounce per medium dog

1,200 mg ai

1 1⁄4 ounce per large dog

Not for use on puppies less than 12 weeks of age. 

Dust entire dog beginning at the head and working back. Make 

sure powder gets down to the skin. 

Lightly dust the dog’s bedding with approximately the same 

amount of powder. 

Repeat treatment of dog and bedding at weekly intervals if 

necessary. 

Use 1⁄2 ounce of powder for a small dog; 1 oz for a medium dog; 

and 1 1⁄4 oz for large dogs. 

47000-123

Cats

Estimated Range: 

43 mg ai, small

100 mg ai, medium

150 mg ai, large

(1.0% ai)

Do not apply to kittens or puppies under 12 weeks old.

Dust powder evenly over the animal and rub thoroughly through 

the hair coat to skin. 

Use 1/3 oz of powder per every 10 pounds of body weight of your 

cat or dog. 

Dogs Do not reapply product for 30 days. 

Estimated Range: 

170 mg ai, small

430 mg ai, medium
Page 14 of 45

Table 4.0. Summary of Registered TCVP Pet Products

EPA Reg. 

No. Use Site Application Rate Use Restrictions

680 mg ai, large

67517-82

Cats

Estimated Range: 

130 mg ai, small

310 mg ai, medium

460 mg ai, large

(3% ai)

Do not use on puppies under 12 weeks of age. 

Dust powder liberally over the animal and rub thoroughly through 

hair coat to skin. 

Use 1/3 oz of powder per every 10 pounds of body weight of your 

cat or dog. 

To control fleas, reapply every 16 days. To control brown dog 

ticks, reapply every 7 days. Dogs

Estimated Range:

510 mg ai, small

1,300 mg ai, medium

2,000 mg ai, large

Pump/Trigger Sprays

2596-125 Dogs

300 mg ai, small

400 mg ai, medium

700 mg ai, large

(1.1% ai)

Do not apply to pets (puppies) less than 6 weeks old. 

Hold bottle upright about 6 inches from pet. Spray lightly until the 

tips of the pet’s hair are moist. Rub spray into animal’s coat. 

Repeat once per week. 

Recommended dosage: Spray 25-30 strokes for a small dog. Spray 

30-40 strokes for a medium dog. Spray 40-70 strokes for a large 

dog. More spray may be needed for longhaired dogs. 1 

2596-126 Cats

250 mg ai, small

350 mg ai, large

(1.1% ai)

Do not apply to pets (kittens) less than 6 weeks old. 

Hold bottle upright about 6 inches from pet. Spray lightly until the 

tips of the pet’s hair are moist. Rub spray into animal’s coat. 

Repeat once per week. 

Recommended dosage: Spray 15-25 strokes for a small cat. Spray 

25-35 strokes for a large cat. More spray may be needed for 

longhaired cats. 1

2596-140

Cats3

(Pump)

51 mg ai, small

71 mg ai, large

(1.1% ai)

Do not use on puppies or kittens less than 12 weeks old. 

Hold bottle upright about 6 inches from pet. Spray lightly until the 

tips of the pet’s hair are moist. Rub spray into animal’s coat. 

Repeat once per week. 

Recommended dosage: Spray 15-25 strokes for a small cat. Spray 

25-35 strokes for a large cat.2

Recommended dosage: Spray 25-35 strokes for a small dog. Spray 

30-40 strokes for a medium dog. Spray 40-70 strokes for a large 

dog.2 

Cats3

(Trigger)

250 mg ai, small

350 mg ai, large

(1.1% ai)

Dogs

(Trigger)

350 mg ai, small

400 mg ai, medium

700 mg ai, large

(1.1% ai)

2596-136 A “Cancellation Order for Section 3 Pesticide Product Registration(s)” was finalized on July 31, 2013 

pertaining to EPA Reg. No. 2596-136, Hartz 2 in 1 Flea and Tick Spray for Cats and Dogs. 

2596-122, 

-123 EPA Reg. Nos. 2596-122 and -123 have been voluntarily cancelled. 

1. Current label language (EPA Reg. No. 2596-125 and 2596-126) allows for more than a prescribed amount of strokes per 

cat/dog. Assessment is based on the amount labelled for each weight range. Any such label language allowing for an 

exceedance should be removed. 

2. The recommended number of strokes as presented for EPA Reg. No. 2596-140 is based on master label amendments proposed 

by the registrant and granted by EPA (March 2014). Previously, a number of strokes per cat/dog was not recommended. The 

maximum number of strokes was considered in the risk assessment for cats and dogs based on animal size. 

3. EPA Reg. No. 2596-140 registered as both a pump spray and trigger spray for cats.

5.0 Residential Exposure and Risk Estimates 

Residential exposures are anticipated from use of TCVP pet products. Exposures are expected 
Page 15 of 45

for adults who apply TCVP products to their pets and from post-application exposures to adults 

and children who may contact previously treated pets. Residential TCVP handler and postapplication exposures are anticipated to be short- (1 to 30 days) to intermediate-term (1 to 6 

months). However, because of the steady state AChE inhibition exhibited by the OPs, steady

state exposures (21 days and longer) were assessed and presented for residential exposures to 

TCVP pet products.

5.1 Residential Handler Exposures

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 assumed to 

complete all elements of an application without use of any protective equipment.

Residential handler exposures to TCVP pet products may occur via the dermal or inhalation 

routes while the product is placed on a cat or dog. A steady state residential handler exposure 

assessment (combined dermal and inhalation) was performed for homeowners applying TCVP 

products to cats/dogs. In addition, a residential handler cancer assessment was conducted. 

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

following exposure scenarios: the application of TCVP pet collars, dusts/powders, and 

pump/trigger sprays to cats and dogs. 

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: The application rates used in the assessment of pet products typically 

represent the maximum amount of active ingredient (ai) that could be applied by weight of the 

treated animal (small, medium, and large). However, this is only possible when the product is 

manufactured for use, or is labeled specifically for different animal weight ranges. If this 

information is not provided, a number of assumptions are used which are described in HED’s 

2012 Residential SOPs (Treated Pets SOP). Application rates for all TCVP pet products are 

presented in Table 4.0. 

For TCVP collars, the applicator is directed to cut off and dispose of any excess length once the 

product is fit and buckled into place. As described in the Treated Pet SOP, because the exact 

length cannot be determined, the corresponding ai loss cannot be quantified and, therefore,

exposure is assessed assuming the full collar length. 

Per the 2012 Treated Pet SOP, it is assumed that residential handlers of pet treatment products 

will treat 2 animals per application. For TCVP dusts/powders, all products identify a specific 

amount to use per animal weight that allows for determination of the maximum application rate. 

For TCVP pump sprays, all registered products direct the user to apply a specific number of 

“strokes” per animal size. In order to determine the amount of ai applied per treatment as 
Page 16 of 45

specified by number of strokes, HED requested additional information from the product 

registrant. Hartz Mountain Corporation provided information regarding the volume of product 

released per stroke for pump and trigger spray products; 0.19 and 0.93 grams, respectively. Only 

trigger spray products are registered for dogs; however, both pump and trigger spray products are 

registered for cats. Additionally, per request of HED, in March 2014 Hartz Mountain 

Corporation amended the master label of EPA Reg. No. 2596-140 to recommend a number of 

strokes per animal size. Previously, a number of strokes per cat/dog were not recommended.

Unit Exposures and Area Treated or Amount Handled: Chemical-specific unit exposure data 

were provided in support of residential handler risk assessment for the dust/powder formulations 

only (MRID 45519601). The study, “Determination of Dermal and Inhalation Exposures to 

Tetrachlorovinphos (TCVP) During the Application of an Insecticide Powder to a Dog,” was 

previously reviewed by the Agency5and determined to be acceptable. This exposure data was 

used as a surrogate to estimate handler exposures from the TCVP dust/powder products. The 

study resulted in average unit exposures for the dermal and inhalation routes of exposure of 

1,700 mg/lb ai and 3.1 mg/ lb ai, respectively. 

In the absence of exposure data for residential handling of pet collars and pump/trigger sprays, 

HED used exposure values from the 2012 Residential SOPs: Treated Pets as a surrogate to 

estimate handler exposures. Surrogate exposure data for a groomer trigger pump spray 

application to dogs was used to estimate handler exposures from TCVP pump spray products. 

No exposure data are available for assessment of handler exposures from the application of 

collars. In the absence of formulation-specific data, exposure data for spot-on applications was 

used to estimate handler exposures from the TCVP collar products. 

Exposure Duration: Residential handler exposure is expected to be short-term in duration. 

Intermediate- and long-term exposures are not likely because of the intermittent nature of 

applications by homeowners. Steady state exposures (21 days and longer) were assessed and 

presented for residential exposures to TCVP pet products because of the steady state AChE 

inhibition exhibited by the OPs. 

Days per Year of Exposure: For the purpose of assessing residential handler cancer exposure/risk

from TCVP product application, HED has assumed 4 days per year for collars, and 6 days per 

year for dusts/powders and pump sprays. The collar is based on a worst-case assumption of a

single application every 3 months. Collar re-treatment intervals range from 3 to 7 months. HED 

assumed a bi-monthly retreatment interval for dusts/powders and pump sprays. 

Years per Lifetime of Exposure: It is assumed that residential handlers would be exposed for 50 

years out of a 78 year lifespan. This factor is routinely used as a conservative estimate of the 

number of years an individual could continually use a single pesticide product. 

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 

 

5 S. Hanley. HED’s Review of Determination of Dermal and Inhalation Exposures to Tetrachlorvinphos (TCVP) 

During the Application of an Insecticide Powder to a Dog. 1/9/02. D278626.
Page 17 of 45

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 Non-Cancer Exposure and Risk Estimate Equations

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

found in Appendix A and/or the 2012 Residential SOPs.

6

Combining Exposure/Risk Estimates

A total ARI approach was required to combine the dermal and inhalation routes of exposure 

because of the different levels of concern (LOCs); dermal exposure (100) and inhalation 

exposure (30). ARIs of less than 1 are risk estimates of concern. The ARI was calculated as 

follows.

Aggregate Risk Index (ARI) = 1÷ [(Dermal LOC ÷ Dermal MOE)+ (Inhalation LOC ÷ Inhalation MOE)]

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

Residential handler (adults) combined steady state dermal and inhalation exposures are not of 

concern to the Agency (i.e., all ARIs are ≥ 1) from application of any registered TCVP pet 

product (Table 5.1.1). 

 

6 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 18 of 45

Table 5.1.1. Residential Handler Non-cancer Exposure and Risk Estimates from Use of TCVP Pet Products

Exposure Scenario Reg. No. Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

(lb ai/pet)

Amount 

Handled 

Daily2

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 ARI7

Application of TCVP 

Collars

2596-49:

Cat

Dermal: 100 120 Negligible

0.0036:

11 gram collar

2 

animals 

treated per 

day

0.0010 7,600

Negligible NA

2596-50, 62:

Dog

0.0061: 

19 gram collar 

0.018 4,500

0.010:

32 gram collar

0.0030 2,700

2596-63:

Cat

0.0048:

15 gram collar

0.0014 5,800

0.0055:

17 gram collar

0.0016 5,100

2596-83:

Cat

0.0039:

12 gram collar

0.0011 7,200

0.0080:

25 gram collar

0.0023 3,500

2596-84:

Dog

0.0061:

19 gram collar

0.0018 4,500

0.010:

32 gram collar

0.0030 2,700

2596-139:

Cat

0.0032:

10 gram collar

0.00093 8,600

2596-139:

Dog

0.016:

50 gram collar

0.0046 1,700

11556-164:

Dog

0.0072:

24 gram collar

0.0021 3,800

11556-165:

Cat

0.0045: 

15 gram collar

0.0013 6,100
Page 19 of 45

Table 5.1.1. Residential Handler Non-cancer Exposure and Risk Estimates from Use of TCVP Pet Products

Exposure Scenario Reg. No. Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

(lb ai/pet)

Amount 

Handled 

Daily2

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 ARI7

Application of TCVP 

Dusts/Powders

2596-78:

Cat

Dermal: 100

Inhalation: 

30

1,700 3.1

0.00062:

small 0.0025 3,200 0.000048 34,000 31

0.0010:

large 0.0042 1,900 0.000080 21,000 18

2596-79; 

Dog

0.0010: 

small 0.0042 1,900 0.000080 21,000 18

0.0021:

medium 0.0084 950 0.00016 10,000 9.2

0.0026: 

large 0.011 760 0.00020 8,300 7.4

47000-123: 

Cat

0.000094:

small 0.00038 21,000 0.0000073 230,000 200

0.00023:

medium 0.00092 8,700 0.000017 95,000 85

0.00034:

large 0.0014 5,800 0.000026 63,000 57

47000-123:

Dog

0.00037:

small 0.0015 5,200 0.000029 57,000 51

0.00094:

medium 0.0038 2,100 0.000073 23,000 20

0.0015:

large 0.0061 1,300 0.00012 14,000 13

67517-82:

Cat

0.00028:

small 0.0011 7,000 0.000022 76,000 68

0.00067:

medium 0.0028 2,900 0.000052 32,000 28

0.0010:

large 0.0041 1,900 0.000078 21,000 19

67517-82:

Dog

0.0011:

small 0.0046 1,700 0.000087 19,000 17

0.0028:

medium 0.011 700 0.00022 7,600 6.8

0.0045: 0.018 440 0.00035 4,700 4.2
Page 20 of 45

Table 5.1.1. Residential Handler Non-cancer Exposure and Risk Estimates from Use of TCVP Pet Products

Exposure Scenario Reg. No. Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

(lb ai/pet)

Amount 

Handled 

Daily2

Dermal Inhalation Total

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6 ARI7

large

Application of TCVP 

Pump/Trigger Sprays

2596-126,

-140:

Cat

(Trigger)

820 3.3

0.00055:

small 

0.0011 7,400 0.000045 36,000 70

0.00077:

medium

0.0015 5,300 0.000064 26,000 50

2596-140

Cat

(Pump)

0.00011:

small

0.00022 36,000 0.0000093 180,000 340

0.00016:

large

0.00031 26,000 0.000013 130,000 240

2596-125, -

140:

Dog

(Trigger)

0.00077:

small

0.0015 5,300 0.000064 26,000 50

0.00088:

medium

0.0017 4,600 0.000073 23,000 43

0.0015:

large

0.0030 2,600 0.00013 13,000 25

1 Based on registered TCVP pet product labels. 

2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/pet) × Area Treated or Amount Handled (pets/day) × Dermal Absorption Factor (9.6 %) ÷ Body 

Weight (80 kg).

4 Dermal MOE = Dermal NOAEL (8.0 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/pet) × Area Treated or Amount Handled (pets/day) ÷ Body Weight (80 kg).

6 Inhalation MOE = Inhalation NOAEL (1.65 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

7 Aggregate Risk Index (ARI) = 1/ ((1 / (Dermal MOE/ Dermal LOC; 100)) + (1/ (Inhalation MOE/ Inhalation LOC; 30))
Page 21 of 45

Residential Handler Cancer Exposure and Risk Estimate Equations

Cancer risk estimates were calculated using a linear low-dose extrapolation approach in which a

Lifetime Average Daily Dose (LADD) is first calculated and then compared with a Q1* that has 

been calculated for TCVP based on dose response data in the appropriate toxicology study (Q1* 

= 1.83 x 10-3(mg/kg/day)-1). Absorbed average daily dose (ADD) levels were used as the basis 

for calculating the LADD values. Dermal and inhalation ADD values were first added together 

to obtain combined ADD values. LADD values were then calculated and compared to the Q1* to 

obtain cancer risk estimates. The algorithms used to estimate the LADD and cancer risk for 

residential handlers can be found in Appendix A.

Summary of Residential Handler Cancer Exposure and Risk Estimates

Estimated residential handler cancer risk estimates range from 10-9to 10-7 (Table 5.1.2).

Table 5.1.2. Residential Handler Cancer Exposure and Risk Estimates from TCVP Pet 

Products

Reg No./ 

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

Pet Collars

2596-49: Cat Any

Adult

7.4E-06 1.3E-08

2596-50, 62: Dog

Small 1.2E-05 2.3E-08

Medium, Large 2.1E-05 3.8E-08

2596-63: Cat

Small 9.8E-06 1.8E-08

Medium, Large 1.1E-05 2.0E-08

2596-83: Cat

Small 7.8E-06 1.4E-08

Medium, Large 1.6E-05 3.0E-08

2596-84: Dog

Small 1.2E-05 2.3E-08

Medium, Large 2.1E-05 3.8E-08

2596-139: Cat Any 6.5E-06 1.2E-08

2596-139: Dog Any 3.3E-05 6.0E-08

11556-164: Dog Any 1.5E-05 2.7E-08

11556-165: Cat Any 9.2E-06 1.7E-08

Dust/Powder

2596-78: Cat

Small

Adult

2.7E-05 5.0E-08

Medium 4.5E-05 8.3E-08

2596-79: Dog

Small 4.5E-05 8.3E-08

Medium 9.0E-05 1.7E-07

Large 1.1E-04 2.1E-07

47000-123: Cat

Small 4.1E-06 7.5E-09

Medium 9.8E-06 1.8E-08

Large 1.5E-05 2.7E-08

47000-123: Dog

Small 1.6E-05 3.0E-08

Medium 4.1E-05 7.5E-08
Page 22 of 45

Table 5.1.2. Residential Handler Cancer Exposure and Risk Estimates from TCVP Pet 

Products

Reg No./ 

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

Large 6.6E-05 1.2E-07

67517-82: Cat

Small 1.2E-05 2.3E-08

Medium 3.0E-05 5.4E-08

Large 4.4E-05 8.1E-08

67517-82: Dog

Small 4.9E-05 9.0E-08

Medium 1.2E-04 2.3E-07

Large 2.0E-04 3.6E-07

Pump/Trigger Sprays

2596-126:

-140: Cat (Trigger)

Small

Adult

1.2E-05 2.2E-08

Large 1.7E-05 3.0E-08

2596-140: 

Cat (Pump)

Small 2.4E-06 4.4E-09

Large 3.4E-06 6.2E-09

2596-125, -140:

Dog (Trigger)

Small 1.7E-05 3.0E-08

Medium 1.9E-05 3.5E-08

Large 3.3E-05 6.1E-08

1 Total Lifetime Average Daily Dose (mg/kg/day) = Dermal LADD (mg/kg/day) + Inhalation LADD (mg/kg/day).

2 Dermal and Inhalation LADD equations provided in Appendix A. 

3 Cancer risk estimates = Total LADD × Q1

*

, where Q1

* = 1.83 x 10-3

(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 

contacting a cat/dog previously treated with TCVP pet products. The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios: 

1) Post-application dermal (adults and children 1 to < 2 years old) exposure from contacting cats 

and dogs treated with TCVP; and 

2) Post-application incidental oral (hand-to-mouth) exposure (children 1 to < 2 years olds only) 

from contacting cats and dogs treated with TCVP.

Residential post-application inhalation exposure is expected to be negligible from TCVP pet 

products and, thus, a quantitative assessment was not performed. Per the 2012 Residential SOPs, 

the combination of low vapor pressure (2.6 x 10-7 mmHg at 25°C) and the small amounts of 

pesticide applied to pets is expected to result in negligible inhalation exposures. 

The lifestages selected for each post-application scenario (i.e., adults and children 1 to < 2 years 

old) are based on an analysis provided in the 2012 Residential SOPs. While not the only 

lifestage potentially exposed for these post-application scenarios, the lifestage that is included in 

the quantitative assessment is health protective for the exposures and risk estimates for all who 

are potentially exposed.
Page 23 of 45

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 

SOPs. Surrogate and chemical-specific residue transfer studies were used for assessment of 

post-application exposures from registered TCVP pet products. These exposure data include the 

following residue transfer studies: propoxur collar (MRID 48589901); and TCVP powder and 

pump spray (MRID 45485501). 

HED previously conducted a data evaluation record (DER) of the TCVP exposure study for 

aerosols, powders, and pump sprays7in 2001. In support of the Agency’s response to the NRDC 

petition, the study has been reevaluated based on current standards of conduct for pet residue 

transfer studies.

8

 The reevaluation of the TCVP residue transfer study resulted in a number of 

changes from the 2001 DER. Table 5.2.1 below presents a comparison of the methods used to 

evaluate the study data.

Table 5.2.1. Comparison of 2001 and Current TCVP Pet Residue Transfer Study Reviews

2001 Review Current Review

Hand wipe residue data were corrected for 

average field fortification recoveries <90%.

Hand wipe residue data were corrected for 

average field fortification recoveries <120%. 

TCVP residues on hands in μg/cm2 were 

calculated using the surface area of the stroking 

area (defined as length of dog x length of study 

participant’s hand).

TCVP residues are calculated in μg/cm2 using the 

surface area of the entire dog, based on the weight 

of the test animal.

The percent of applied TCVP dislodged by the 

hand following treatment was calculated based on 

the amount of TCVP residue on the stroking area, 

which was determined from extrapolating residues 

detected in fur samples from a shaved area to the 

area of the stroking area. 

The percent of applied TCVP transferred to the 

hand was calculated based on the total amount of 

active ingredient applied to the dog (calculated as 

the amount removed from container in grams x 

actual percent active ingredient in test product).

Regression analyses were conducted using the 

residue data in μg/cm2. 

The revised regression analyses were conducted 

using the percent of applied dose transferred to 

the hand.

It should be noted that the TCVP powder and pump spray post-application exposure study was 

not conducted in a manner reflective of current standards that require a defined stroking 

procedure and greater number of petting simulations. That is, the pet is to be stroked in a single 

motion with the grain of the fur starting with both sides (along the ribcage) of the [cat/dog] and

followed by the same motion along the back (dorsally) from the base of the neck to the tail. The 

two sides and back, in this order, account for one petting simulation. A total of 20 petting 

 

7 S. Hanley. Re-evaluation of Determination of the Dislodgeability of Tetrachlorvinphos (TCVP) from the Fur of 

Dogs Following the Application of an Insecticide Powder, Pump Spray or Aerosol. 3/25/02. D277543.

8 W. Britton. Tetrachlorvinphos: Reevaluation of “HED’s Review of Determination of the Dislodgeability of 

Tetrachlorvinphos (TCVP) from the Fur of Dogs Following the Application of an Insecticide Powder, Pump Spray 

or Aerosol; MRID 45485501. 5/16/14. D420285. 
Page 24 of 45

simulations (or 60 stroking motions) are currently required. In the TCVP post-application 

exposure study, the dogs were stroked only one side of treated dog’s back from head to rump 

five times. However, the study was reflective of current policy regarding pet residue transfer 

studies at the time that it was conducted. In order to account for the differences between the 

TCVP post-application exposure study and the currently recommended standard, the Agency 

used the maximum observed percent residue transfer on the day of product application (Day 0) 

for both formulations for exposure and risk quantification. Typically, the Agency assesses postapplication risk with use of the mean percent residue transfer measured on Day 0; the use of the 

maximum value results in a more health protective risk assessment. Even though the postapplication exposure study methods have evolved, the TCVP study employed a rigorous 

collection method and is not anticipated to underestimate exposure. 

The 2012 Residential SOPs: Treated Pets recommends assessment of post-application exposures 

using day of application (i.e., Day 0) residue transfer -- defined as fraction application rate (FAR)

in the 2012 SOPs. Day of application (Day 0) percent residue transfer values (as referenced from 

the above studies) used for exposure/risk quantification are as follows: pet collars, 0.072%; 

dusts/powders, 0.048% (maximum observed); and pump sprays, 0.81% (maximum observed).

For purpose of quantification of estimated TCVP post-application cancer exposures/risks, HED 

recommends use the average percent residue transfer of all days sampled in the propoxur collar9

and TCVP dust/powder and pump spray studies. For the TCVP collar, HED used an average FAR

(of 28 days sampling in the propoxur collar study) of 0.013% to represent 180 days exposure per 

year. Due to the reasons described above with use of the TCVP dust/powder and pump spray 

exposure data, HED used an average of the maximum observed percent residue transfer for each 

day tested for calculation of cancer exposures/risks resulting in an FAR of 0.022% and 0.18% for 

dusts/powders and pump sprays, respectively. 

Exposure Duration: Residential post-application exposure is expected to be short- and 

intermediate-term for dust/powders and pump/trigger sprays. For pet collars, post-application 

exposures is expected to be long-term (greater than 6 months) due to the potential for extended 

usage in more temperate parts of the country, and the longer active lifetime of pet collar 

products. Again, because of the steady state AChE inhibition exhibited by the OPs, steady state 

exposures (21 days and longer) were assessed and presented for residential post-application 

exposures to TCVP pet products.

Hand-to-Mouth Event Frequency: The 2012 Residential SOPs recommend a frequency estimate 

of 20 as the modeled number of hand-to-mouth events per hour for children 1-2 years old. There 

are currently no data available that specifically address the number of hand-to-mouth events that 

occur relative to the amount of time that a child spends with a pet. As a result, the estimate for 

frequency of hand-to-mouth events in indoor environments is based on the Xue et al. (2007)10

meta-analysis of child hand mouthing frequency. The indoor data were selected, even though 

 

9 S. Shelat. Propoxur: Data Evaluation Record for the Study “Determination of Transferable Residues of Propoxur 

from the Hair of Dogs Wearing collars Impregnated with Propoxur – Final Report.” 10/12/12. D393899.

10 Xue, J., Zartarian, V., Moya, J., Freeman, N., Beamer, P., Black, K., Tulve, N., Shalat, S. (2007), A MetaAnalysis of Children's Hand-to-Mouth Frequency Data for Estimating Nondietary Ingestion Exposure. Risk 

Analysis, 27(2):411-420.
Page 25 of 45

child exposure to treated pets can occur either indoors or outdoors, because the indoor data result 

in a greater frequency of contacts and, therefore, a more health protective risk assessment. 

Residential Post-application Non-Cancer Exposure and Risk Equations

The algorithms used to estimate cancer and non-cancer exposure and dose for residential postapplication can be found in Appendix A and/or the 2012 Residential SOPs.

11

Combining Exposure and Risk Estimates

HED combines risk values resulting from separate routes of exposure when it is likely they can 

occur simultaneously based on the use pattern and the behavior associated with the exposed 

population, and if the hazard associated with the points of departure is similar across routes. A 

common toxicological endpoint, RBC AChE inhibition, exists for dermal and incidental oral 

routes of exposure to TCVP; thus, exposures should be combined for all routes of exposure. 

Summary of Residential Post-Application Non-Cancer Exposure and Risk Estimates

Residential post-application steady state adult dermal exposure and children 1 to < 2 years old 

combined dermal and incidental oral exposures are not of concern to the Agency (i.e, all MOEs 

are ≥ 100) for all TCVP pet products assessed (Table 5.2.2).

Table 5.2.2. Residential Post-Application Non-Cancer Exposure and Risk Estimates from TCVP 

Products

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal 

Size

Dose 

(mg/kg/day)2 MOEs3 Total

MOE4

Route of Exposure

Pet Collars

2596-49: 

Cat

Adult Dermal

1,650

Small 0.0038 2,100

Medium 0.0023 3,500 X

Large 0.0014 5,600

Children 

1 < 2

Dermal Small 0.0097 830 750 Incidental Oral 0.0010 7,900

Dermal Medium 0.0058 1,400 1,300 Incidental Oral 0.00061 13,000

Dermal Large 0.0036 2,200 2,000 Incidental Oral 0.00038 21,000

2596-50, 

62: 

Dog

Adult Dermal

2,770 Small 0.0032 2,500

X

4,670 Large 0.0015 5,400

Children 

1 < 2

Dermal 2,770 Small 0.0081 980 890 Incidental Oral 0.00085 9,400

Dermal 4,670 Large 0.0037 2,100 1,900 Incidental Oral 0.00039 21,000

2596-63: 

Cat

Adult Dermal

2,190 Small 0.0051 1,600

X

2,480 Large 0.0021 3,700

Children Dermal 2,190 Small 0.013 620 560

 

11 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 26 of 45

Table 5.2.2. Residential Post-Application Non-Cancer Exposure and Risk Estimates from TCVP 

Products

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal 

Size

Dose 

(mg/kg/day)2 MOEs3 Total

MOE4

Route of Exposure

1 < 2 Incidental Oral 0.0013 6,000

Dermal 2,480 Large 0.0055 1,500 1,400

Incidental Oral 0.00057 14,000

2596-83: 

Cat

Adult Dermal

1,750 Small 0.0040 2,000

X

3,650 Large 0.0032 2,500

Children 

1 < 2

Dermal 1,750 Small 0.010 780 710 Incidental Oral 0.0011 7,500

Dermal 3,650 Large 0.0080 1,000 910 Incidental Oral 0.00084 9,600

2596-84: 

Dog

Adult Dermal

2,770 Small 0.0032 2,500

X

4,670 Large 0.0015 5,400

Children

1 < 2

Dermal 2,770 Small 0.0081 980 890 Incidental Oral 0.00085 9,400

Dermal 4,670 Large 0.0037 2,100 1,900

Incidental Oral 0.00039 21,000

2596-139: 

Cat

Adult Dermal

1,460

Small 0.0034 2,400

Medium 0.0020 4,000 X

Large 0.0013 6,300

Children

1 < 2

Dermal Small 0.0086 930 840 Incidental Oral 0.00089 9,000

Dermal Medium 0.0051 1,600 1,400 Incidental Oral 0.00054 15,000

Dermal Large 0.0032 2,500 2,300 Incidental Oral 0.00033 24,000

2596-139: 

Dog

Adult Dermal

7,300

Small 0.0084 950

Medium 0.0036 2,200 X

Large 0.0023 3,500

Children

1 < 2

Dermal Small 0.021 370 340 Incidental Oral 0.0022 3,600

Dermal Medium 0.0092 870 790 Incidental Oral 0.00096 8,400

Dermal Large 0.0058 1,400 1,300 Incidental Oral 0.00061 13,000

11556-164: 

Dog

Adult Dermal

3,290

Small 0.0038 2,100

Medium 0.0016 4,900 X

Large 0.0010 7,700

Children

1 < 2

Dermal Small 0.0096 830 750 Incidental Oral 0.0010 8,000

Dermal Medium 0.0041 1,900 1,700 Incidental Oral 0.00043 19,000
Page 27 of 45

Table 5.2.2. Residential Post-Application Non-Cancer Exposure and Risk Estimates from TCVP 

Products

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal 

Size

Dose 

(mg/kg/day)2 MOEs3 Total

MOE4

Route of Exposure

Dermal 

Large

0.0026 3,000

2,700 Incidental Oral 0.00027 29,000

11556-165:

Cat

Adult Dermal

2,060

Small 0.0047 1,700

Medium 0.0028 2,800 X

Large 0.0018 4,500

Children

1 < 2

Dermal Small 0.012 660 600 Incidental Oral 0.0013 6,400

Dermal Medium 0.0072 1,100 1,000 Incidental Oral 0.00075 11,000

Dermal Large 0.0045 1,800 1,600 Incidental Oral 0.00047 17,000

Dusts/Powders

47000-123:

Dog 

Adult Dermal

170 Small 0.0035 2,300

430 Medium 0.0038 2,100 X

680 Large 0.0038 2,100

Children

1 < 2

Dermal 170 Small 0.0090 890 450 Incidental Oral 0.0087 920

Dermal 430 Medium 0.0097 830 420 Incidental Oral 0.0093 860

Dermal 680 Large 0.0098 810 410 Incidental Oral 0.0095 840

47000-123:

Cat

Adult Dermal

43 Small 0.0018 4,500

100 Medium 0.0025 3,200 X

150 Large 0.0024 3,400

Children

1 < 2

Dermal 43 Small 0.0045 1,800

900 Incidental Oral 0.0043 1,800

Dermal 100 Medium 0.0065 1,200

620 Incidental Oral 0.0063 1,300

Dermal 150 Large 0.0061 1,300

670 Incidental Oral 0.0059 1,400

2596-78: 

Cat

Adult Dermal 280 Small 0.012 690 X

470 Large 0.0073 1,100

Children

1 < 2

Dermal 280 Small 0.030 270 140 Incidental Oral 0.029 280

Dermal 470 Large 0.019 430 220 Incidental Oral 0.018 450

2596-79:

Dog

Adult Dermal

470 Small 0.0097 820

940 Medium 0.0083 960 X

1,200 Large 0.0066 1,200

Children Dermal 470 Small 0.025 320 160
Page 28 of 45

Table 5.2.2. Residential Post-Application Non-Cancer Exposure and Risk Estimates from TCVP 

Products

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal 

Size

Dose 

(mg/kg/day)2 MOEs3 Total

MOE4

Route of Exposure

1 < 2 Incidental Oral 0.024 330

Dermal 940 Medium 0.021 380 190 Incidental Oral 0.021 390

Dermal 1,200 Large 0.017 470 240 Incidental Oral 0.016 490

67517-82:

Dog

Adult Dermal

510 Small 0.011 760

1,300 Medium 0.011 710 X

2,000 Large 0.012 690

Children

1 < 2

Dermal 510 Small 0.027 300 150 Incidental Oral 0.026 310

Dermal 1,300 Medium 0.029 280 140 Incidental Oral 0.028 290

Dermal 2,000 Large 0.030 270 140 Incidental Oral 0.028 280

67517-82:

Cat

Adult Dermal

130 Small 0.0053 1,500

310 Medium 0.0076 1,100 X

460 Large 0.0071 1,100

Children

1 < 2

Dermal 130 Small 0.014 590 300 Incidental Oral 0.013 610

Dermal 310 Medium 0.020 410 210 Incidental Oral 0.019 430

Dermal 460 Large 0.018 440 220 Incidental Oral 0.018 450

Pump/Trigger Spray

2596-126, 

140: Cat

(Trigger)

Adult Dermal

250 Small 0.0065 1,200

X

350 Large

0.0034 2,300

Children

1 < 2

Dermal 250 Small 0.017 480 440 Incidental Oral 0.0017 4,700

Dermal 350 Large0.0087 920 830

Incidental Oral 0.00090 8,900

2596-140: 

Cat

(Pump)

Adult Dermal

51 Small 0.0013 6,000

X

71 Large 0.00070 12,000

Children

1 < 2

Dermal 51 Small 0.0034 2,400 2,200 Incidental Oral 0.00035 23,000

Dermal 71 Large 0.0018 4,500 4,100

Incidental Oral 0.00018 43,000

2596-125, 

-140: Adult Dermal 350 Small 0.0045 1,800

X

400 Medium 0.0022 3,600
Page 29 of 45

Table 5.2.2. Residential Post-Application Non-Cancer Exposure and Risk Estimates from TCVP 

Products

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal 

Size

Dose 

(mg/kg/day)2 MOEs3 Total

MOE4

Route of Exposure

Dog

(Trigger)

700 Large 0.0025 3,200

Children

1 < 2

Dermal 350 Small 0.012 690 620 Incidental Oral 0.0012 6,600

Dermal 400 Medium 0.0057 1,400 1,300 Incidental Oral 0.00059 14,000

Dermal 700 Large 0.0063 1,300 1,200 Incidental Oral 0.00066 12,000

1 Based on registered TCVP pet products as detailed in Table 4.0.

2 Dose (mg/kg/day) equations provided in Appendix A.

3 MOE = PoD (8.0 mg/kg/day) ÷ Dose (mg/kg/day).

4 Total MOE = 1 ÷ (1 ÷ Dermal MOE) + (1 ÷ Incidental Oral MOE), where applicable.

Residential Post-application Cancer Exposure and Risk Estimate Equations

As was done for residential handlers, post-application cancer risk estimates for adults 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 TCVP based on dose response data in 

the appropriate toxicology study (Q1* = 1.83 x 10-3(mg/kg/day)-1). The algorithms used to 

estimate the LADD and cancer risk for residential post-application exposure can be found in 

Appendix A. 

It should be noted that in the past, cancer risk assessments have assumed that children are no 

more sensitive than adults to carcinogens (i.e., no adjustment was made to children's exposure 

estimates in calculating a cumulative lifetime exposure). More recently, the Agency's 

"Guidelines for Carcinogen Risk Assessment" (USEPA, 2005) and “Supplemental Guidance for 

Assessing Susceptibility from Early-Life Exposure to Carcinogens” (USEPA, 2005) proposed 

age-dependent adjustment factors to be applied to children's exposure. These age-dependent 

factors are applied only to carcinogens shown to have a mutagenic mode of action. In general, 

most carcinogenic pesticides have not been shown to act through a mutagenic mode of action,

and thus separate assessment of children and adults is not warranted. Any pesticide found to be a 

carcinogen acting through a mutagenic mode of action should be dealt with on a case by case 

basis, and such an assessment should follow the Agency’s 2005 guidance. The mutagenicity 

database for TCVP suggests that this chemical is not mutagenic in both the gene mutation assay 

and primary rat hepatocyte unscheduled DNA synthesis assay and, therefore, only adult cancer 

risk estimates have been estimated. 

Days per Year of Exposure: 

For purpose of estimating adult dermal cancer risks, exposure was assumed for 180 of 365 total 

days per year. This factor is used as a health protective estimate of the number of days that an 

individual could be exposed to a treated animal per year of product use. The recommendation of 

6 months exposure is conservative, particularly when paired with the assumption that this 

exposure duration is repeated for 50 years during an adult’s lifetime. 
Page 30 of 45

Years per Lifetime of Exposure:

It is assumed that adults would be exposed for 50 years out of a 78 year lifespan. This factor is 

routinely used as a conservative estimate of the number of years an individual could continually 

use a single pesticide product. 

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. 

Summary of Residential Post-application Cancer Exposure and Risk Estimates

Adult residential post-application dermal cancer risk estimates range from 10-8to 10-6(detailed 

below in Table 5.2.3).

Table 5.2.3. Residential Post-Application Cancer Exposure and Risk Estimates from 

TCVP Pet Products

Animal Type Animal 

Size Lifestage LADD1,2 Cancer Risk Estimate3

Collar

2596-49: Cat

Small

Adult

2.2E-04 4.0E-07

Medium 1.3E-04 2.4E-07

Large 8.1E-05 1.5E-07

2596-50,62: Dog

Small 1.8E-04 3.3E-07

Large 8.4E-05 1.5E-07

2596-83: Cat

Small 2.3E-04 4.2E-07

Large 1.8E-04 3.3E-07

2596-139: Cat

Small 1.9E-04 3.5E-07

Medium 1.2E-04 2.1E-07

Large 7.2E-05 1.3E-07

11556-164: Dog

Small 2.2E-04 4.0E-07

Medium 9.3E-05 1.7E-07

Large 5.9E-05 1.1E-07

11556-165: Cat

Small 2.7E-04 5.0E-07

Medium 1.6E-04 3.0E-07

Large 1.0E-04 1.9E-07

2596-84: Dog Small 1.8E-04 3.3E-07

Large 8.4E-05 1.5E-07

2596-139: Dog

Small 4.8E-04 8.8E-07

Medium 2.1E-04 3.8E-07

Large 1.3E-04 2.4E-07

2596-63: Cat Small 2.9E-04 5.3E-07
Page 31 of 45

Table 5.2.3. Residential Post-Application Cancer Exposure and Risk Estimates from 

TCVP Pet Products

Animal Type Animal 

Size Lifestage LADD1,2 Cancer Risk Estimate3

Large 1.2E-04 2.2E-07

Dust/Powder

47000-123: Dog

Small

Adult

5.1E-04 9.3E-07

Medium 5.5E-04 1.0E-06

Large 5.6E-04 1.0E-06

47000-123: Cat

Small 2.5E-04 4.7E-07

Medium 3.7E-04 6.7E-07

Large 3.4E-04 6.3E-07

2596-78: Cat

Small 1.7E-03 3.1E-06

Large 1.1E-03 1.9E-06

2596-79: Dog

Small 1.4E-03 2.6E-06

Medium 1.2E-03 2.2E-06

Large 9.6E-04 1.8E-06

67517-82: Dog

Small 1.5E-03 2.8E-06

Medium 1.6E-03 3.0E-06

Large 1.7E-03 3.1E-06

67517-82: Cat

Small 7.6E-04 1.4E-06

Medium 1.1E-03 2.0E-06

Large 1.0E-03 1.9E-06

Pump/Trigger Spray

2596-126, 140: Cat

(Trigger)

Small

Adult

4.6E-04 8.3E-07

Large 2.4E-04 4.4E-07

2596-140: Cat

(Pump)

Small 9.3E-05 1.7E-07

Large 4.9E-05 8.9E-08

2596-125, -140: Dog

(Trigger)

Small 3.2E-04 5.8E-07

Medium 1.6E-04 2.9E-07

Large 1.7E-04 3.2E-07

1 Total Lifetime Average Daily Dose (mg/kg/day) = Dermal LADD (mg/kg/day) + Inhalation LADD (mg/kg/day).

2 Dermal and Inhalation LADD equations provided in Appendix A. 

3 Cancer risk estimates = Total LADD × Q1*, where Q1* = 1.83 x 10-3 (mg/kg/day)-1

5.3 Residential Risk Characterization

The evaluation of the potential residential post-application health risks from exposures to 

cats/dogs treated with TCVP pet products is conservative. The risk estimates calculated are 

based upon protective assumptions of TCVP hazard, product application rates, durations of 

exposure, and contact with the treated animal, and they make use of the best available post-
Page 32 of 45

application exposure data.

Application Rate: The application rates used in the assessment of pet products represent the 

maximum amount of TCVP that could be applied by weight of the treated animal (small, 

medium, and large) for TCVP collars, dusts/powders, and pump/trigger sprays. 

For TCVP collars, the applicator is directed to cut off and dispose of any excess length once the 

product is fit and buckled into place. As described in the Treated Pet SOP, because the exact 

length cannot be determined, the corresponding TCVP loss cannot be quantified and, therefore, 

exposure is assessed assuming the full collar length. While this approach may result in an 

overestimate of collar application rate, it ensures protection of users who may contact dogs 

wearing an uncut TCVP collar. 

For TCVP dusts/powders, all products identify a specific amount to use per animal weight that 

allows for determination of the maximum application rate. For TCVP pump/trigger sprays, all 

registered products direct the user to apply a specific number of “strokes” per animal size. In 

order to determine the amount of ai applied per treatment as specified by number of strokes, 

HED requested additional information from the product registrant. Hartz Mountain Corporation 

provided information regarding the volume of product released per stroke for pump and trigger 

spray products; 0.19 and 0.93 grams, respectively. Only trigger spray products are registered for 

dogs; however, both pump and trigger spray products are registered for cats. Additionally, per 

request of HED, in March 2014 Hartz Mountain Corporation amended the master label of EPA 

Reg. No. 2596-140 to recommend a number of strokes per animal size. Previously, a number of 

strokes per cat/dog was not recommended. The maximum number was considered in the risk 

assessment for cats and dogs and based on animal size.

Exposure Data: It is HED policy to use the best available data to assess exposure. Where 

chemical- or formulation-specific exposure data were available, these data were used to conduct 

the assessment of residential handler and post-application exposures or integrated with other data 

as appropriate. The exposure estimates based on the use of these data are the most accurate 

representation of exposures anticipated from use of TCVP pet products and are not expected to 

underestimate residential risks. 

All residential handler exposure estimates are based on the values recommended in the 2012 

SOPs for Residential Exposure Assessment (SOPs). For the application of TCVP dust/powder 

formulation exposure scenario, chemical-specific exposure monitoring data are available (MRID 

45519601). These data were previously reviewed by the Agency and determined to be 

acceptable for use in risk assessment. In fact, these data have been incorporated into the

calculation of the unit exposure value associated with this scenario in the 2012 Residential SOPs. 

A carbaryl dust/powder exposure study is also included in the SOP unit exposure 

recommendation for the dust/powder exposure scenario as described in the Residential SOPs. 

For purpose of the residential handler dust/powder assessment, only the TCVP unit exposure 

data were used. For further information regarding how the exposure estimates were determined, 

please refer to the 2012 Residential SOPs where the process is explained in detail.

For the assessment of residential post-application exposures from registered TCVP products, 
Page 33 of 45

surrogate and chemical-specific transferable residue transfer studies were used which are 

believed to best represent the potential exposures from TCVP use. These residue data were 

collected from treated dogs after treatment with 1) TCVP aerosol12, powders, and pump spray

formulations (MRID 45485501) and 2) a pet collar containing the active ingredient propoxur 

(MRID 48589901). HED previously completed a review of the TCVP aerosol, powder, and 

pump spray formulation residue transfer study for (MRID 45485501) in 2001. That study was

reevaluated based on current standards of conduct for pet residue transfer studies. This

reevaluation of the TCVP transferable residue study resulted in a number of changes from the 

2001 review. These differences are illustrated in Table 5.2.1 of this document.

The 2012 Residential SOPs: Treated Pets recommends that the fraction of applied residues which 

come off of a companion animal on the day of application (i.e., Day 0) should serve as the basis 

for assessment of post-application exposures. This input is defined as fraction application rate 

(FAR) in the 2012 SOPs. The day of application percent residue transfer values resulting from the 

above referenced studies used for exposure/risk quantification are as follows: pet collars, 

0.072% (arithmetic mean); dusts/powders, 0.048% (maximum observed); and pump/trigger

sprays, 0.81% (maximum observed). 

The TCVP powder and pump spray post-application exposure study was not conducted in a 

manner reflective of current standards that require a defined stroking procedure and greater

number of petting simulations. That is, the pet (cat/dog) should be stroked in a single motion 

with the grain of the fur starting with both sides (along the ribcage) of the animal and followed 

by the same motion along the back (dorsally) from the base of the neck to the tail. The two sides 

and back, in this order, account for one petting simulation. A total of 20 petting simulations (or 

60 stroking motions) are currently required. In the TCVP post-application exposure study, the 

dogs were stroked only one side of treated dog’s back from head to rump five times. It is also 

notable that the dogs were stroked with a bare hand, rather than with the currently required 

transferable collection method, cotton gloves worn over a mannequin hand. Transferable 

residues were collected for analysis in the TCVP post-application exposure study from the bare 

hand using a methanol wipe. In the current method, the cotton gloves are removed from the 

mannequin hand for analysis. The mannequin hand is not analyzed, but acts only as a residue 

collection tool to avoid direct contact with the treated animal. Despite these differences, the 

TCVP powder and pump spray post-application exposure study was reflective of current policy 

regarding pet residue transfer studies at the time that it was conducted. 

For the reasons described in Section 5.2 of this document, HED used the maximum observed 

percent residue transfer on the day of product application (Day 0), as opposed to the average, for 

both formulations for exposure/risk quantification. This approach results in residue transfer for 

pump/trigger sprays comparable to the arithmetic mean percent residue transfer observed from 

the analysis of all liquid formulated product data sets presented in the 2012 Residential SOPs; 

0.81% and 0.96%, respectively. The TCVP dust/powder study is the only data available for this 

pet product formulation and, thus, HED has no basis of comparison; however, the data are

acceptable for risk quantitation and are the best available for the product type. 

No exposure data are available for assessment of post-application exposures from the use of 

 

12 Note: The TCVP aerosol per product formulation is no longer a registered use. 
Page 34 of 45

TCVP pet collars. Two post-application exposure studies have been submitted to the Agency in 

support of residential pet collar uses, the aforementioned propoxur pet collar study and a recently 

submitted deltamethrin pet collar residue transfer study (MRID 49350101).

13

 Both studies were 

conducted in a manner consistent with current standards and are recommended for use in risk 

quantitation. The propoxur pet collar study resulted in mean percent residue transfer on Day 0 in 

excess of that of the deltamethrin study; 0.072% and 0.003%, respectively. The more 

conservative mean percent residue transfer resulting from the propoxur study was selected for 

use as a surrogate for estimation of TCVP post-application risks. 

In comparison to other formulations used for pet pest control (e.g., dusts, spot-ons, sprays), the 

pet collar formulation is unique and results in considerably lower percent residue transfer values. 

When other pet product formulations are applied to a treated pet, it can be reasonably assumed 

that the entire amount of that applied (i.e., the application rate) is available on the hair coat of the

animal for transfer to the exposed individual. For example, the labeled amount of the TCVP 

pump/trigger spray product can be used directly in the assessment of exposure/risk because it is 

assumed this amount is available on the surface for contact. Pet collar formulations operate by 

slowly releasing the ai from the collar medium, making them efficacious for pest treatment over 

longer periods of time. Due to this activity, it can be difficult for the risk assessor to determine 

the amount which is initially available on the animal because the majority is retained within the 

collar. Accordingly, the propoxur and deltamethrin pet collar study results in residue transfer 

much less than that from other, liquid formulated products.

For residential handler exposure assessment for TCVP collar products, exposure data for spot-on 

applications was used as a surrogate to estimate handler exposures. For the reasons described in 

the preceding paragraph, the use of the spot-on applicator exposure data is highly conservative. 

For purpose of quantification of estimated TCVP post-application cancer exposures/risks, HED 

used the mean percent residue transfer of all days sampled in the propoxur collar and TCVP 

dust/powder and pump spray studies. For the TCVP collar, HED used an average FAR (of 28 

days sampling in the propoxur collar study) of 0.013% to represent 180 days exposure per year. 

Due to the reasons described above with use of the TCVP dust/powder and pump spray exposure 

data, HED used an average of the maximum observed percent residue transfer for each day tested 

for calculation of cancer exposures/risks resulting in an FAR of 0.022% and 0.18% for 

dusts/powders and pump sprays, respectively. 

While the use of the maximum observed percent residue transfer on Day 0 is not typically 

undertaken for non-cancer or cancer residential exposure assessment, it allows for use data best 

representative of the exposure potential from TVCP pet products while ensuring a conservative, 

health protective assessment of residential risks.

Pet Contact: For the purpose of determining exposure to treated pets, the 2012 Residential SOPs 

make use of transfer coefficients (TCs). TC is an exposure rate for a selected activity which 

involves contact with a source, such as children playing with treated pets or on treated turf. The 

TC concept is a long-standing established approach used to estimate residential, as well as 

 

13 M. Collantes. Deltamethrin: Data Evaluation Record for the Study “Deltamethrin: two-month dislodgeable 

residue study of deltamethrin in beagle dogs treated with Scalibor® Protector Band.” 6/4/14. D420043.
Page 35 of 45

occupational exposures, and is the basis for the Agency’s post-application exposure guidelines.

14

A TC is derived by taking the ratio of study volunteer dermal exposure per unit time (mg/hr), and 

the concurrent measure of residue transfer. Ideally, dermal exposure is based on an activities 

representative of the use pattern and residue transfer is determined by use of an established 

method specific to the use pattern. For pet exposures, TCs can be defined as animal surface area 

contact per unit time (cm2/hr). 

Currently, there is no exposure study available using representative, or typical adult and child 

activities with pets and a concurrent transferable residue (TR) measure. In the absence of direct 

exposure data for residential activities with pets, the Agency concluded that studies conducted to 

monitor pet grooming activities are likely to result in a highly protective estimate of pet contact 

relative to contact associated with petting, hugging, or sleeping with a pesticide-treated pet.

These data were gathered while human volunteers applied dust/powders and shampoo products

to various dogs of differing sizes and fur lengths. Since these individuals extensively handled 

the dogs, it is expected that their resulting exposures are higher than would be reasonably 

anticipated from routine contact with treated pets. The volunteers in the shampoo study, who 

were professional groomers, shampooed 8 dogs for 5 minutes each, rinsed, and lifted them to 

counters for drying and combing resulting in very high exposures. In the dust study, volunteers 

applied dust via shaker can to 8 dogs each and then rubbed the dusts into the dogs’ coats. The 

applicator studies were not conducted in a manner which measured TR, or active ingredient per 

surface area. Therefore, the residue available on the animal for transfer was predicted by 

multiplying the arithmetic mean fraction of application rate from the analysis of all liquid 

formulated product data sets presented in the 2012 Residential SOPs, 0.96%. This approach has 

the effect of increasing TC estimates, thus resulting in TC values which are more protective of 

human health. Furthermore, the selection of the mean value, in lieu of the screening level FAR

value, 2%, further increases the TC estimates with use of the dust and shampoo studies. 

Exposure Time: The exposure time (ET) assumption used to assess residential post-application 

exposure to TCVP pet products is derived from a study which sought to evaluate the times that 

individuals spend performing different activities around the home. Based upon the 2012 

Residential SOPs: Treated Pet SOP, the point estimates recommended for adult and child ET 

with pets are 0.77 and 1 hours, respectively. In the study, animal care is defined as “care of 

household pets including activities with pets, playing with the dog, walking the dog and caring 

for pets of relatives, and friends.” The data identified the time spent with an animal while 

performing household activities as recorded in 24 hour diaries by study volunteers. While the 

activities defined do not necessarily represent the time volunteers were actively engaged in 

constant contact with the animal as is implicit in the post-application dermal and incidental oral 

algorithms, the data are the most accurate representation of time spent with pets available and, 

therefore, it is assumed that contact is continual throughout the timed activity. HED assumes the 

ET value reflects a reasonable high end estimate of time spent in contact with a dog treated with 

TCVP pet products. 

When use of the study data are coupled with high end assumptions of pet contact, the result is an 

exposure assessment that inherently implies vigorous, continual contact for the entire duration of 

 

14 http://www.ecfr.gov/cgi-bin/textidx?SID=6bfd4539761be8d5b20dfbf6bc19b9d0&node=40:25.0.1.1.9.9&rgn=div6
Page 36 of 45

contact. While it is possible that an adult or child may be in close contact with a pet 

intermittently throughout the day, they would not be actively engaged in the highly vigorous 

contact implied by use of the TCs based on the applicator exposure data for the full exposure 

duration assumed. Further, it is possible that adults or children may be exposed from sleeping 

with a treated pet; however, they are not actively engaged in a high level of contact, or the 

repeated mouthing behaviors exhibited by children during waking hours, which are inherently 

assumed in the assessment conducted. 

Hazard: The toxicology database for TCVP is complete and adequate to support the residential 

assessment from TCVP pet product use. For TCVP, AChE inhibition is the most sensitive 

endpoint in the toxicology database in multiple species, durations, lifestages, and routes. TCVP 

has low acute (lethality) toxicity by the oral, dermal, and inhalation routes of exposure. It is 

classified as a Group C possible human carcinogen by the Agency with a linear low-dose 

approach for quantification of risk using the oral slope factor (Q1*) of 1.83 x 10-3(mg/kg/day)-1. 

TCVP is not mutagenic and immunotoxicity was not observed at levels that exceed the limit 

dose. The FQPA SF was reduced to 1X since there is no evidence of sensitivity of the young 

animal in the pre- and post-natal studies compared to the adult, and there are no data gaps. 

Consistent with risk assessments for other AChE-inhibiting compounds, HED conducted a BMD 

analysis for TCVP using a benchmark response (BMR) level of 10%, and has thus calculated 

BMD10 and BMDL10 values. The use of the 10% BMR is derived from a combination of 

statistical and biological considerations. A power analysis was conducted by the Office of 

Research and Development (ORD) on over 100 brain AChE datasets across more than 25 OPs as 

part of the OP cumulative risk assessment (CRA) (USEPA, 2002). This analysis demonstrated 

that 10% is a level that can be reliably measured in the majority of rat toxicity studies. In 

addition, the 10% level is generally at or near the limit of sensitivity for discerning a statistically 

significant decrease in ChE activity in the brain compartment and is a response level close to the 

background brain ChE level. With respect to biological considerations, a change in 10% brain 

AChE inhibition is protective for downstream clinical signs and apical neurotoxic outcomes. 

Based on a robust BMD analysis evaluating a broad representation of the TCVP toxicity 

database, points of departure were selected for the assessment of the major residential routes of 

exposure; dermal (handler and post-application), incidental oral (post-application only), and 

inhalation (handler only). 

For the dermal risk assessment, a steady state PoD was selected from the subchronic oral toxicity 

study in rats. Since an oral study was selected, a DAF of 9.57% was used for the route-to-route 

extrapolation. The DAF is based on the results of a dermal penetration study in rats. The use of 

the rat dermal absorption data is considered conservative because rats tend to have more 

permeable skin that humans (3 – 10X). Therefore, the use of the rat DAF based on the rat 

dermal penetration study likely leads to an overestimation of residential dermal exposures. 

Indirect Incidental Oral Exposures: An assessment of indirect incidental oral exposures resulting 

from children putting objects or other toys in their mouth that potentially have residue from 

contact with treated pets (i.e., object-to-mouth exposures) was not conducted. The 2012 

residential SOPs state that hand-to-mouth and object-to-mouth incidental oral exposures 

assessments should be conducted for treatments to indoor environments and lawns/turf only. For 
Page 37 of 45

these exposure scenarios, children’s hand-to-mouth exposures are expected from direct contact 

with treated surfaces (i.e., treated turf and carpets/hard floors) and object-to-mouth exposures are 

expected due to the potential for secondary exposures from mouthing objects that may have been 

in contact with the treated surface. With use of the methods described in the indoor 

environments and lawn/turf SOPs, the quantification of hand-to-mouth exposures following 

direct contact with the treated surface always results in exposures of a greater magnitude and, as 

a result, a more health protective assessment of risk (i.e., a lower MOE) than from indirect 

object-to-mouth exposures.

When the dermal and incidental oral exposure routes share a common toxicological endpoint, as 

is the case for TCVP, risk estimates are combined for these routes. The incidental oral exposure 

scenarios (i.e., hand-to-mouth and object-to-mouth) are considered inter-related and it is likely 

that they occur interspersed amongst each other across time. Accordingly, choosing the highest 

of the incidental oral exposure scenarios is protective of both. Further, combining both of the 

incidental oral exposure scenarios with the dermal exposure scenario would be unrealistic 

because of the highly conservative nature of each individual assessment. Therefore, the hand-tomouth exposure scenario, which has the highest estimated incidental oral risk, is combined with 

the dermal post-application exposure and is considered a protective estimate of children’s 

exposures following pesticide usage. This approach is consistent with that used for assessment 

of post-application exposures from TCVP pet product usage.

5.4 Residential Risk Estimates for Use in Aggregate Assessment

Tables 5.1.1, 5.2.2 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 TCVP.

 The recommended residential exposure for use in the adult aggregate non-cancer risk 

assessment is combined (dermal and inhalation) exposures from applications to large 

dogs with a dust/powder product (EPA Reg. No. 65717-82). 

 The recommended residential exposure for use in the children 1<2 years old non-cancer 

aggregate assessment is combined (dermal and hand-to-mouth exposures) from postapplication exposure to either small cats or large dogs from EPA Reg. Nos. 2596-78 and 

67517-82, respectively. 

 The recommended residential exposure for use in the adult aggregate cancer assessment 

is dermal exposure from the post-application exposure to large dogs from EPA Reg. No. 

67517-82 (dose is 1.7E-03 mg/kg/day).
Page 38 of 45

Table 5.4. Recommendations for the Residential Exposures for the TCVP Aggregate Risk 

Assessment1

Lifestage

(Scenario)

Dose (mg/kg/day) Risk Estimates

Dermal Inhalation Oral Total2 Dermal Inhalation Oral Total 

MOE3 ARI4

Residential Handler

Adult 0.018 0.00035 N/A 0.018 440 4,700 N/A N/A 4.2

Residential Post-application

Child 0.030 N/A 0.029 0.059 270 N/A 280 140 N/A

Cancer Exposure

Adult 1.7E-03 N/A N/A 1.7E-03 N/A N/A N/A N/A N/A

1 Bolded worst-case risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Total Dose (mg/kg/day) = Dermal Dose + Inhalation Dose + Incidental Oral Dose (where applicable).

3 Total MOE = 1 ÷ (1 ÷ Dermal MOE) + (1 ÷ Incidental Oral MOE).

4 ARI = 1÷ [(Dermal LOC (100) ÷ Dermal MOE) + (Inhalation LOC (30) ÷ Inhalation MOE)].

5.5 Spray Drift

This assessment has not been conducted for the TCVP pet use products that are unlikely to result 

in spray drift. Further, spray drift is not anticipated from the occupational use of TCVP for 

direct application to livestock or livestock premises. 

5.6 Residential Bystander Post-Application Inhalation Exposure

Residential post-application inhalation exposure is expected to be negligible from TCVP pet 

products and, thus, a quantitative assessment was not performed. Per the Residential SOPs, the 

combination of low vapor pressure (2.6 x10-7 mmHg at 25°C) and the small amounts of pesticide 

applied to pets is expected to result in negligible levels of chemical in the air, and therefore 

negligible inhalation exposures. 
Page 39 of 45

Appendix A: Algorithms Used to Calculate Residential Non-Cancer and Cancer Risk 

Estimates

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.

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).

TR =

AR ∗ FAR

SA

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:
Page 40 of 45

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) Unique for each product

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 

(recommended point estimate)

Non-Cancer

Collar (Propoxur Study): 0.00072

Dust/Powder (TCVP): 0.00048

Pump Spray (TCVP): 0.0081

Cancer

Collar (Propoxur Study): 0.00013

Dust/Powder (TCVP): 0.00022

Pump Spray (TCVP): 0.0018

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

Post-application Hand-to-Mouth Exposure Algorithm

Exposure from hand-to-mouth activity is calculated as follows (based on algorithm utilized in 

SHEDS-Multimedia):
Page 41 of 45

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

(intervals/hr) 4

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 Children 1 < 2 years 20
Page 42 of 45

Table A.2. Treated Pets – Inputs for Residential Post-application Hand-to-Mouth Exposure

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

hour

(events/hr)

old

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

Cancer Exposure Algorithm

Exposure/Dose Amortization:

An accurate estimate of exposure over the course of weeks, years or a lifetime is difficult to 

predict as exposure likely differs from one day to the next due to product-specific application 

regimens, residue dissipation, human behavior and activity patterns, and the extent to which an

individual’s exposure varies due to behavior changes. Approaches for amortizing dose over 

various exposure durations are explained in more detail in Section 1.3 of the 2012 Residential 

SOPs; however an example would be amortization of an individual’s daily dose over their 

lifetime necessary for calculating exposures for cancer risk assessments. This amortized dose is

known as the lifetime average daily dose (LADD) and it can be calculated as follows:

LADD = D * EF * ET

AT * CF

where:

LADD = lifetime average daily dose (dermal + inhalation, mg/kg-day);

D = dose (mg/kg-day);

EF = exposure frequency (i.e., frequency of product use) (days/year);

ET = exposure time (years);

AT = averaging time (i.e., life expectancy) (years); and

CF = conversion factor (365 days/year).

Table A.3. Treated Pets – Inputs for Cancer Exposure/Risk

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

EF Exposure Frequency (days/year)

Handlers: Collars, 4; Dusts/Powders and 

Pump/Trigger Sprays, 6

Post-application (all formulations): 180 

ET Exposure Time (years) 50

AT Averaging Time (years) 78

CF Conversion Factor (days/year) 365
Page 43 of 45

Appendix B: Summary of OPP’s ChE Policy & Use of BMD Modeling

OPP’s ChE policy (USEPA, 200015) describes the manner in which ChE data are used in human 

health risk assessment. The following text provides a brief summary of that document to provide 

context to points of departure selected. 

AChE can be inhibited in the central or peripheral nervous tissue. Measurements of AChE or 

cholinesterase (ChE) inhibition in peripheral tissues (e.g., liver, diaphragm, heart, lung etc.) are 

rare. As such, experimental laboratory studies generally measure brain (central) and blood 

(plasma and red blood cell [RBC]) ChE. Blood measures do not represent the target tissue, per 

se, but are instead used as surrogate measures for peripheral toxicity in studies with laboratory 

animals or for peripheral and/or central toxicity in humans. In addition, RBC measures represent 

AChE, whereas plasma measures are predominately butyryl-ChE (BuChE). Thus, RBC AChE 

data may provide a better representation of the inhibition in target tissues. As part of the dose 

response assessment, evaluations of neurobehavior and clinical signs are performed to consider 

the dose response linkage between AChE inhibition and apical outcomes.

Refinements to OPP’s use of ChE data have come in the implementation of BMD approaches in 

dose response assessment. Beginning with the OP cumulative risk assessment (CRA), OPP has 

increased its use of BMD modeling to derive PoDs for AChE inhibiting compounds. Most often 

the decreasing exponential empirical model has been used. 

OPP does not have a defined benchmark response (BMR) for OPs. However, the 10% level has 

been used in the majority of dose response analyses conducted to date. This 10% level 

represents a 10% reduction in AChE activity (i.e., inhibition) compared to background (i.e., 

controls). Specifically, the BMD10 is the estimated dose where ChE is inhibited by 10% 

compared to background. The BMDL10 is the lower confidence bound on the BMD10. 

The use of the 10% BMR is derived from a combination of statistical and biological 

considerations. A power analysis was conducted by the ORD on over 100 brain AChE datasets 

across more than 25 OPs as part of the OP CRA (USEPA, 2002). This analysis demonstrated 

that 10% is a level that can be reliably measured in the majority of rat toxicity studies. In 

addition, the 10% level is generally at or near the limit of sensitivity for discerning a statistically 

significant decrease in ChE activity in the brain compartment and is a response level close to the 

background brain ChE level. With respect to biological considerations, a change in 10% brain 

AChE inhibition is protective for downstream clinical signs and apical neurotoxic outcomes. 

RBC AChE inhibition data tend to be more variable than brain AChE data. OPP begins its BMD 

analyses using the 10% BMR for RBC AChE inhibition. However, BMRs up to 20% could be 

considered on a case by case basis, as long as such PoDs are protective for brain AChE 

inhibition, potential peripheral inhibition, and clinical signs of neurotoxicity.

 

15 USEPA (2000) Office of Pesticide Programs, US Environmental Protection Agency, Washington DC 20460. 

August 18, 2000 Office of Pesticide Programs Science Policy of The Use of Data on Cholinesterase Inhibition

for Risk Assessments of Organophosphorous and Carbamate Pesticides.

http://www.epa.gov/oppfead1/trac/science/cholin.pdf
Page 44 of 45

Appendix C: Results for BMD/BMDL modeling for TCVP 

BMD analyses were performed with EPA’s Benchmark Dose Software (Version 2.4) using an 

exponential model for continuous data16. The Hill model was also performed for some data sets, 

but did not result in the best fit for the data. The data selected for evaluation consisted of 

decreased brain and red blood cell (RBC) cholinesterase (ChE) activities. Data were analyzed 

from a 21-day oral toxicity study (MRID 45570601), a 13-week subchronic oral toxicity study 

(MRID 43371201), and a 2 year chronic oral toxicity study (MRID 42980901); a gestational 

comparative cholinesterase assay (CCA; MRID 48291101); and a 28-day inhalation toxicity 

study (MRID 48803501). All data from these studies were considered; however, some data were 

not amenable to BMD analysis. 

OPP has used the exponential model for modeling AChE activity for the OP and N-methyl 

carbamate cumulative risk assessments and with multiple single chemical risk assessments of 

ChE-inhibiting pesticides. Model runs for ChE activity were conducted with an appropriate 

benchmark response level (10%). As such the BMD10 (estimated dose to result in 10% change 

from background levels) and BMDL10 (the lower 95% confidence level on the BMD10) are 

provided in the output. Statistical (e.g., goodness of fit values) and graphical results were used in 

model evaluation. 

The results of the repeated oral and inhalation dosing BMD analyses are summarized below in 

Table C.1. Good model fit (p>0.1) was obtained for the majority of the analyses, with any 

exceptions being noted. 

For exposure to repeated doses the BMDL10 for ChE inhibition in the adult female RBCs were 

similar in the 13-week subchronic study and the 21-day oral toxicity study (8.0 mg/kg/day vs 6.7 

mg/kg/day, respectively). Although data from the shorter duration study resulted in a slightly 

lower BMDL, visual examination of the modeled data provided greater confidence in the 

13-week study. For inhalation exposure, the adult male was about twice as sensitive as the adult 

female (0.023 mg/L in males vs 0.050 mg/L in females).

Table C.1. Results of BMD Exponential Modeling for Brain and RBC ChE Data on TCVP, Repeated 

Oral Dosing Studies in Rats, Ranging in Duration from 21 days to 2 years.

TCVP Study Age/Sex Compartment

BMD Results

BMD10 BMDL10

MRID 43371201

13W Oral – 13 

Weeks

Adult Male Brain No dose response (analysis not performed)

Adult 

Female Brain No dose response

Adult Male RBC 61.6 mg/kg/day 26.3 mg/kg/day

Adult 

Female RBC 10.5 mg/kg/day 8.0 mg/kg/day

 

16 J. Bever. Tetrachlorvinphos: Benchmark Dose Analysis of Subchronic and Chronic Studies to Support Derivation 

of Points of Departure. 5/20/2014. TXR # 0056970. D420286.
Page 45 of 45

Table C.1. Results of BMD Exponential Modeling for Brain and RBC ChE Data on TCVP, Repeated 

Oral Dosing Studies in Rats, Ranging in Duration from 21 days to 2 years.

TCVP Study Age/Sex Compartment

BMD Results

BMD10 BMDL10

MRID 42980901

Chronic Oral 

Tox – 364, 539, 

and 721 Days

Adult 

Female RBC No dose-response effect was observed at 364, 539, or 721 days

MRID 45570601

21D Oral Tox –

21 Days

Adult 

Female

Brain 14.7 mg/kg/day 12.2 mg/kg/day

RBC 9.9 mg/kg/day 6.7 mg/kg/day

MRID 48803501

28D Inhalation –

28 Days

Adult Male RBC 0.122 mg/L 0.023 mg/L

Adult 

Female RBC 0.394 mg/L 0.050 mg/L