UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: December 2I,2015 

SUBJECT : Tetrachlorvinphos (TCVP) Human Health Draft Risk Assessment (ORA) for 

Registration Review 

PC Code: 083 70 I , 083 702 

Petition No.: NA 

Risk Assessment Type: Single Chemical 

Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: D4 l l 095 

Registration Nos.: NA 

Regulatory Action: Registration 

Review 

Case No.: 1321 

CAS No.: 22248-79-9 

40 CFR: § 180.252 

FROM: Danette Drew, Chemist/Risk Assesso~~~~-A.....---

Linda Taylor, Ph.D. Toxicologi ~ 

Risk Assessment Branch V N I 

Health Effects Division (HED, 7509P) 

And 

Wade Britton, MPH, Environmental Health Scientist 

Risk Assessment Branch IV 

Health Effects Division (HED, 7509P) .· 

THROUGH: Michael Metzger, Branch Chief ~ f~y .(). / 4~ Risk Assessment Branch v NII \ l y I/ r 

And 

TO: 

Health Effects Division (HED, 7509P) 

HED RARC (Risk Assessment Review ~°1m~e~~ewers: 

Michael A. Doherty, Ph.D., Chemist ~~ ,, 

Monique M. Perron, Sc.D., Toxicologist ~ ./_.tNV--

Health Effects Division (HED, 7509P) 

James Parker, Chemical Review Manager 

Thomas Moriarty, RMS I 

Risk Management and Implementation Branch I 

Pesticide Re-evaluation Division (7508P) 

Attached is HED's human health risk assessment in support of the registration review of the 

insecticide tetrachlorvinphos. 
Page 2 of 152

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

2.0 HED Recommendations..................................................................................................... 11

2.1 Data Deficiencies........................................................................................................ 11

2.2 Tolerance Considerations........................................................................................... 11

2.2.1 Enforcement Analytical Method............................................................................. 11

2.2.2 International Harmonization ................................................................................... 12

2.2.3 Recommended Tolerances...................................................................................... 12

2.3 Label Recommendations ............................................................................................ 15

2.3.1 Recommendations from Residue Reviews ............................................................. 15

3.0 Introduction........................................................................................................................ 15

3.1 Chemical Identity ....................................................................................................... 15

3.2 Physical/Chemical Characteristics ............................................................................. 16

3.3 Pesticide Use Pattern .................................................................................................. 16

3.4 Anticipated Exposure Pathways................................................................................. 16

3.5 Consideration of Environmental Justice..................................................................... 16

4.0 Hazard Characterization and Dose-Response Assessment................................................ 17

4.1 Toxicology Studies Available for Analysis................................................................ 17

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)................................... 18

4.2.1 Dermal Absorption.................................................................................................. 18

4.3 Toxicological Effects.................................................................................................. 18

4.3.2 Critical Durations of Exposure ............................................................................... 20

4.4 Literature Review on Neurodevelopment Effects ...................................................... 22

4.5 Safety Factor for Infants and Children (FQPA Safety Factor)................................... 27

4.5.1 Completeness of the Toxicology Database............................................................. 28

4.5.2 Evidence of Neurotoxicity ...................................................................................... 28

4.5.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 28

4.5.4 Residual Uncertainty in the Exposure Database..................................................... 28

4.6 Toxicology Endpoint and Point of Departure Selections........................................... 29

4.6.1 Dose-Response Assessment.................................................................................... 29

4.6.2 Recommendations for Combining Routes of Exposure for Risk Assessment........ 32

4.6.3 Cancer Classification and Risk Assessment Recommendation.............................. 32

4.6.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment............................................................................................................................ 33

4.7 Endocrine Disruption.................................................................................................. 36

5.0 Dietary Exposure and Risk Assessment ............................................................................ 37

5.1 Metabolite/Degradate Residue Profile........................................................................ 37

5.1.1 Summary of Plant and Animal Metabolism Studies............................................... 37

5.1.2 Summary of Environmental Degradation ............................................................... 37

5.1.3 Comparison of Metabolic Pathways....................................................................... 37

5.1.4 Residues of Concern Summary and Rationale........................................................ 38

5.2 Residue Chemistry and Food Residue Profile............................................................ 39

5.3 Water Residue Profile................................................................................................. 40

5.4 Dietary Risk Assessment............................................................................................ 41

5.4.1 Description of Residue Data Used in Dietary Assessment..................................... 41

5.4.2 Percent Crop Treated Used in Dietary Assessment ................................................ 42

5.4.3 Acute Dietary Risk Assessment.............................................................................. 43
Page 3 of 152

5.4.4 Steady State Dietary Risk Assessment ................................................................... 43

5.4.5 Cancer Dietary Risk Assessment............................................................................ 44

5.4.6 Summary of Dietary (Food and Drinking water) Exposure and Risk Assessment..... 45

6.0 Residential and Non-Occupational Exposure/Risk Characterization ................................ 45

6.1 Residential Handler Exposure .................................................................................... 48

6.2 Residential Post-Application Exposure...................................................................... 50

6.3 Non-Occupational Spray Drift Exposure and Risk Estimates.................................... 54

6.4 Residential Bystander Post-Application Inhalation Exposure.................................... 54

7.0 Aggregate Exposure/Risk Characterization....................................................................... 54

7.1 Acute Aggregate Risk................................................................................................. 54

7.2 Steady State Aggregate Risk ...................................................................................... 54

7.3 Cancer Aggregate Risk............................................................................................... 60

8.0 Occupational Exposure/Risk Characterization ..................................................................... 62

8.1 Occupational Handler Exposure/Risk Estimates (Non-Cancer and Cancer).............. 62

8.2 Occupational Post-application Exposure/Risk Estimates........................................... 65

9.0 Public Health and Pesticide Epidemiology Data ............................................................... 65

10.0 Cumulative Exposure/Risk Characterization................................................................... 66

11.0 EPA References................................................................................................................. 66

12.0 Appendices......................................................................................................................... 67

Appendix A. Toxicology Profile.................................................................................................. 69

Appendix B. Results for BMD/BMDL modeling for TCVP..................................................... 80

Appendix C. Physical/Chemical Properties for Tetrachlorvinphos............................................. 82

Appendix D. TCVP and Metabolites............................................................................................ 83

Appendix E. International MRLs and U.S. Tolerances............................................................... 85

Appendix F. Summary of Residential Handler Non-Cancer Exposures and Risks................. 88

Appendix G. Summary of Residential Handler Cancer Exposure and Risk Estimates............... 93

Appendix H. Summary of Residential Post-Application Non-Cancer Exposure and Risk 

Estimates 95

Appendix I. Summary of Residential Post-Application Cancer Exposure and Risks........... 103

Appendix J. Summary of Occupational Handler Exposures and Risks ............................... 107

Appendix K. Summary of Occupational Handler Cancer Risk Estimates............................. 120

Appendix L. Summary of TCVP Labels and Use Directions ............................................... 134

Appendix M. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and HumanEquivalent Doses ........................................................................................................................ 150
Page 4 of 152

1.0 Executive Summary

The insecticide tetrachlorvinphos (TCVP) [(Z)-2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl 

phosphate] is a member of the organophosphate (OP) class of pesticides. TCVP is used as a 

dermal or oral treatment to livestock (i.e., cattle, swine, poultry and horses) and their premises, in 

kennels, outdoors as a perimeter treatment, and as a flea treatment on cats and dogs. 

Formulations for pet use include collars, dusts/powders, and pump and trigger sprays. The other 

uses include dusts (D), emulsifiable concentrates (EC), feed through (solid and liquid food 

additives), feed blocks, and wettable powders (WP). Human exposure to TCVP in food may 

occur as a result of consuming residues in animal commodities. Exposure may also occur from 

drinking water that may contain TCVP residues as a result of some use patterns. Residential 

exposures may occur as a result of applying flea products to pets (cats and dogs) or contacting 

treated pets. Occupational exposures may occur during application of TCVP to livestock or their 

premises, or during outdoor perimeter or kennel treatments. Occupational exposures may also 

occur to veterinarians and pet groomers. Exposure via spray drift is not anticipated based on the 

current use patterns.

The most recent risk assessment for TCVP was a residential pet use assessment completed in 

November 2014 (W. Britton, 11/05/14, D420283)

1

. The current TCVP human health risk 

assessment takes into account, where appropriate, arguments presented in the Natural Resources 

Defense Council, Inc.’s (NRDC) Aug. 5, 2015 Opening Brief in NRDC v. EPA, Case No. 15-

70025 (9th Cir.) (Opening Brief), which was filed as a result of the 2014 residential pet product 

assessment and EPA’s subsequent denial of NRDC’s 2009 petition to cancel all TCVP pet 

products. (The EPA point-by-point response to NRDC comments can be found in D4305892.) 

The current TCVP human health risk assessment reflects the following changes since the 2014 

residential assessment:

 Inclusion of the 10X FQPA safety factor/uncertainty factor. 

 There is no non-cancer dermal hazard for TCVP.

 A female-specific body weight, 69 kg, is used for assessment of adult (inhalation) 

exposures instead of the average adult body weight of 80 kg.

 Use of newer pet residue data for pet collars that result in more conservative estimates 

of residue transfer and exposure than the data used in the 2014 risk assessment. 

Residential post-application assessments for TCVP pet collar uses are performed 

using data from two recently submitted pet collar residue transfer studies (an amitraz 

pet collar study3(herein referred to as “the amitraz study”) and a literature study 

using TCVP pet collars (Davis, 20084, herein referred to as “the Davis study”).

 

1 W. Britton, 11/05/14, D420283, Residential Exposure Assessment in Response to the Natural Resources Defense 

Council Petition to Cancel All Pet Uses for Tetrachlorvinphos.

2 W. Britton, 12/21/15, D430589, Tetrachlorvinphos (TCVP): Responses to Arguments Presented in the Natural 

Resources Defense Council, Inc.’s (NRDC) Aug. 5, 2015 Opening Brief in NRDC v. EPA, Case No. 15-70025 (9th

Cir.)

3 MRID 49468801: Determination of Transferable Residues of Amitraz from the Hair of Dogs Following the 

Application of the Preventic® Collar.

4 Davis, M. et. al., Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the 

Organophosphorus Insecticide Tetrachlorvinphos. Journal of Exposure Science and Environmental Epidemiology. 

(2008) 18, 564-57)
Page 5 of 152

 Because it cannot be confirmed at this time if TCVP pet collar products are

manufactured as liquid or solid formulations, the exposures to TCVP pet collar 

products are assessed 1) assuming all collars may be a liquid formulation and 2) 

assuming all collars may be a solid (dust) formulation.

Hazard 

TCVP is a member of the OP class of pesticides. For TCVP, like other OPs, the initiating event 

in the adverse outcome pathway/mode of action (AOP/MOA) 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. TCVP 

does not require metabolic activation to an oxon to inhibit AChE; i.e., the parent compound is 

the active form inhibiting AChE. OPs also exhibit 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. OP AChE studies of 2-3 weeks 

generally show the same degree of inhibition as those of longer duration (i.e., up to 2 years of 

exposure). Therefore, a steady state assessment based on 21 days of exposure may be conducted 

in place of the traditional chronic or long-term assessments. The steady state point of departure 

is protective of any exposure duration longer than 21-days, including chronic exposure, since 

cholinesterase inhibition does not increase after reaching maximum inhibition or steady state.

The toxicology database for TCVP is complete for risk assessment. TCVP has cholinesterase data 

across multiple lifestages, durations, and routes for both red blood cell (RBC) and brain 

cholinesterase inhibition. There are acceptable studies available for toxicity endpoint and point of 

departure (POD) selection. For TCVP, RBC AChE inhibition is the most sensitive endpoint and is 

the endpoint from which the PODs for all TCVP exposure routes and durations were selected. 

There is no evidence of quantitative or qualitative sensitivity in the developmental rat and rabbit 

study or in the gestational (fetus) or juvenile (postnatal day; PND11) components of the 

comparative cholinesterase assay (CCA) study. In the acute and repeated comparative 

cholinesterase assays, juvenile rats (PND 11 and PND 21), pregnant dams, fetuses, and nonpregnant females show similar results in both RBC and brain AChE activity. At the lowest tested 

dose of 75 mg/kg/day in the acute CCA study, there was little difference in RBC or brain AChE 

inhibition between the PND11, PND21, or young adult (PND42). Similarly, the PND11 and 

PND21 rats in the CCA study are similarly sensitive as adult rats exposed to a single dose of 50 

mg/kg from a separate peak inhibition study. The repeat dosing phase of the CCA also 

demonstrates the lack of sensitivity in AChE inhibition in the juvenile (PND11) rats. Furthermore, 

the fetus is not more sensitive than the pregnant dam. Therefore, points of departure that are based 

on adult AChE data are also protective of the postnatal and gestational lifestages.

High quality AChE data for the dermal and inhalation routes are also available and allow for route 

specific evaluation. RBC AChE inhibition was observed in both sexes in the inhalation study (brain 

AChE was not assessed), while no inhibition of RBC or brain AChE was observed in the dermal 
Page 6 of 152

study up to the limit dose. A non-cancer dermal assessment is not required for TCVP; however, a 

cancer dermal assessment is required. 

TCVP is classified as a Group C possible human carcinogen (based on statistically significant 

increases in combined hepatocellular adenoma/carcinoma in female mice) 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.

Whereas parent compound TCVP is the residue of concern for AChE inhibition, TCVP plus 

metabolites containing the 2,4,5 trichlorobenzene moiety are the residues of concern for cancer 

assessment.

Uncertainty Factors

For TCVP, as for other OPs, the FQPA safety factor (SF) of 10X has been retained for infants, 

children, youths, and women of childbearing age for all exposure scenarios due to uncertainty in 

the human dose-response relationship for neurodevelopmental effects (see Section 4.4). 

For the acute and steady state dietary assessments, a total uncertainty factor of 1000X is 

appropriate for infants, children, youths and females of childbearing age (10X to account for 

interspecies extrapolation and 10X for intraspecies variation and the 10X FQPA SF). The only 

population subgroup for dietary exposure scenarios for which the FQPA SF is not retained is 

adults 50-99 years of age; therefore, the total uncertainty factor for that population is 100X.

A total uncertainty factor of 1000X is appropriate for residential incidental oral exposures (10X 

for interspecies extrapolation, 10X for intraspecies variation, and a 10X FQPA SF). A total 

uncertainty factor of 300X is appropriate for all inhalation exposures (3X for interspecies 

extrapolation, 10X for intraspecies variation, and a 10X FQPA SF for residential assessments or a 

10X database uncertainty factor for occupational assessments to protect potentially pregnant 

female workers due to uncertainty in the human dose-response relationship for 

neurodevelopmental effects (see Section 4.4)).

Tolerance/ MRL

Tolerances for residues of TCVP are established under 40 CFR §180.252 for livestock 

commodities based on oral feed-through and direct dermal uses on livestock (cattle, swine, and 

poultry). The residues of concern for tolerance enforcement are tetrachlorvinphos, des-O-methyl 

tetrachlorvinphos, 1-(2,4,5-trichlorophenyl)ethanol (free and conjugated forms), 2,4,5-

trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)ethanediol (frequently abbreviated as 

TCVP, TCVPdeme, TCPEol , TCPEone, and TCPEdiol, respectively). The current tolerance 

expression under 40 CFR §180.252 includes all of these residues except des-O-methyl 

tetrachlorvinphos; this metabolite should be included in the tolerance expression. The current 

tolerance levels should be updated in the 40 CFR as discussed in Section 2.2.3.

There are no Codex maximum residue limits (MRLs) established or proposed for residues of 

TCVP. Canada has established MRLs for plant (apple and grape) and livestock commodities. 

The differences in U.S. and Canadian residue definitions prohibit harmonization.
Page 7 of 152

Dietary Risk Assessment

Acute (TCVP), steady state (TCVP), and cancer (TCVP plus metabolites containing the 2,4,5 

trichlorobenzene moiety) dietary (food and drinking water) exposure and risk assessments were 

conducted using the DEEM-FCID v3.16 model. The dietary exposure analyses for TCVP are 

mostly refined. The only food forms included in the analyses are based on animal commodities. 

The food residues were based upon U. S. Department of Agriculture’s Pesticide Data Program 

(USDA PDP) monitoring data except in a couple of instances where no appropriate PDP data 

were available (i.e., high-end residues from poultry direct dermal application studies were used 

for poultry fat and poultry skin). The Biological and Economic Analysis Division (BEAD) of 

OPP provided percent livestock treated information. Model-derived estimated drinking water 

concentrations (EDWCs) were provided by the Environmental Fate and Effect Division (EFED).

For acute and cancer dietary analyses, the EDWCs were included as single point estimates. For 

the steady state analysis, the entire distribution of 21-day average water concentrations from a

thirty year simulation was used; this refinement was done for the purpose of aggregating the 

steady state residential and dietary exposures.

The acute and steady state dietary (food and drinking water) exposure estimates are below 

HED’s level of concern (<100 % of the acute population adjusted dose (aPAD) or the steady 

state population adjusted dose (ssPAD)) for the U.S. population and all population subgroups. 

The most highly exposed population subgroup was children (3-5 years old) at 73% of the aPAD

and 43% of the ssPAD. 

The cancer dietary (food and drinking water) risk estimate for adults from lifetime exposure to 

TCVP and its metabolites containing the 2,4,5 trichlorobenzene moiety is 1 x 10-6.

Residential Risk Assessment

Residential exposures (handler and post-application) are anticipated from the use of TCVP pet 

products for dogs and cats (collars, dusts/powders, and pump/trigger sprays). Exposures are 

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

to adults and children who may contact previously treated pets. The lifestages selected for each 

residential scenario [i.e., adults (using female body weight) and children 1 to < 2 years old] are 

health protective for the exposures and risk estimates for any other potentially exposed 

lifestage.

Handler

Dust/Powder and Pump/Trigger Spray: All residential handler (adults) non-cancer (steady 

state) inhalation risks estimated for the TCVP pet dust/powder and pump/trigger spray 

formulations are not of concern (i.e., all MOEs are > 300; LOC=300). Residential handler 

estimated cancer risks (combined dermal and inhalation) for TCVP dusts/powders range from 

10-8to 10-7, and for pump/trigger sprays range from 10-9to 10-8. 

Pet Collars: All residential handler (adults) non-cancer (steady state) inhalation risks estimated 

for the TCVP pet collars (whether assessed as liquid or dust formulations) are not of concern 

(i.e., all MOEs are > 300; LOC=300).
Page 8 of 152

Residential handler cancer risks (inhalation and dermal combined) estimated for TCVP pet 

collars are all in the 10-8 range when assuming a liquid formulation and are all in the 10-7range 

when assuming a dust formulation. 

Post-Application

Since there is no non-cancer dermal hazard for TCVP and post-application inhalation exposures 

to treated pets are negligible, a quantitative non-cancer post-application exposure assessment was 

not performed for adults; there are no residential non-cancer risk estimates of concern for adults 

contacting pets treated with TCVP products.

Dust/Powder and Pump/Trigger Spray: Residential post-application non-cancer child 

(incidental oral) exposures to pets treated with TCVP pump/trigger sprays do not result in risk 

estimates of concern (i.e., MOEs are > 1,000; LOC=1000). However, child incidental oral 

exposures to pets treated with TCVP dust/powder products are estimated to be of concern for 14 

of the 17 total exposure scenarios assessed (i.e., MOEs are < 1,000; LOC =1000). Residential 

post-application (adult) cancer risks estimated for TCVP pump/trigger sprays range from 10-7to 

10-6and, for TCVP dust/powder products estimated cancer risks are 10-7. 

Pet Collars: The post-application assessments for the TCVP pet collars were performed 

assuming pet collars could be either liquid or solid (dust) formulations, and using residue transfer 

data from two available collar studies (the amitraz study and the Davis study). Data from both 

studies have been included because the Davis study has not yet undergone review by the Human 

Studies Review Board (HSRB); the study is scheduled for review at the next HSRB meeting in

January 2016. Until the Davis study undergoes a complete review by the HSRB, any

assumptions, risk estimates or conclusions using the Davis study are considered preliminary.

The post-application exposure and risk estimates for the various pet collar assumptions are 

provided below:

Liquid formulation/Amitraz study assumption: Post-application child non-cancer 

incidental oral risk estimates are not of concern (i.e., MOEs are > 1,000; LOC=1000). 

Estimated adult post-application cancer risks range from 10-7 to 10-6. 

Liquid formulation/Davis study assumption: One of the 23 scenarios assessed for postapplication child non-cancer incidental oral risk is of concern (MOE = 650; LOC=1000). 

Estimated adult post-application cancer risks range from 10-6to 10-5. 

Solid (Dust) formulation/Amitraz study assumption: Post-application child non-cancer 

incidental oral risk estimates are of concern for all of the TCVP pet collar exposure 

scenarios assessed (i.e., MOEs are < 1,000; LOC=1000). All estimated adult postapplication cancer risks are estimated to be 10-5

.

 

Solid (Dust) formulation/Davis study assumption: Quantitative assessments were not 

performed assuming collars are dust formulations and using the Davis study since the 

mean residue transfer measured in the Davis study was greater than that in the amitraz 

study; therefore, post-application exposures from TCVP pet collars would be greater, and 
Page 9 of 152

MOEs lower, when using the Davis study than those resulting from using the amitraz 

study (which are of concern for children).

Spray Drift

A quantitative spray drift assessment was not conducted because the use of TCVP for direct 

animal treatment to livestock and their premises, in kennels, outdoors as a perimeter treatment, 

and as a flea treatment on cats and dogs are either 1) not applied via aircraft, groundboom, or

airblast equipment or 2) for applications to poultry buildings with groundboom equipment, the 

use is indoors and not anticipated to be a significant source of spray drift. 

Aggregate Risk Assessment

Acute

The acute aggregate risk assessment includes only dietary (food and drinking water) exposures. 

There are no acute aggregate risk estimates of concern.

Steady State

The steady state aggregate risk assessment combines steady state exposures from food, drinking 

water, and residential uses. The TCVP steady state aggregate assessment was performed for 

adult handlers (applying pet collars, dust/powders, and pump/trigger sprays) and children postapplication activities (contacting treated pets). All pet collar products were assessed as both a 

liquid formulation and as a solid (dust) formulation.

Handler: Residential handler (adult) steady state aggregate (food, water, residential) risk 

estimates for all TCVP pet product scenarios (collars, dust/powders, and pump/trigger 

sprays) are not of concern (Aggregate Risk Index (ARI) ≥ 1).

Post-application: For the TCVP dust/powder pet products, the steady state postapplication aggregate assessments result in 16 of the 17 scenarios with risk estimates of 

concern (MOEs < 1000) for children. For all TCVP pump/trigger spray product 

scenarios, steady state post-application aggregate risk estimates are not of concern. 

Residential post-application (children) steady state aggregate risk estimates for all TCVP 

pet collar scenarios are not of concern (MOEs > 1000) when assuming collars are liquid 

formulations and using data from the amitraz study. Assuming liquid formulation and 

using the Davis study, 8 of the 23 collar scenarios resulted in aggregate MOEs of 

concern. Assuming collars are solid (dust) formulations and using the amitraz study, all 

23 scenarios resulted in aggregate MOEs of concern. Quantitative assessments were not 

performed assuming collars are dust formulation and using the Davis study; those MOEs 

would be even lower than for the dust/amitraz assessments (which are of concern). 

Cancer

The cancer aggregate risk assessment combines residential and dietary (food and drinking water)

expected lifetime exposures for adults. For TCVP, a cancer aggregate assessment was performed 

for adult handlers (applying TCVP pet products) and adult post-application activities (contacting 

treated pets). Pet collar products were assessed as both a liquid formulation and as a solid (dust)
Page 10 of 152

formulation.

Handler: For the handler cancer aggregate, all registered pet product scenarios (collars, 

dust/powders, and pump/trigger sprays) result in residential handler cancer aggregate 

(residential and dietary) risk estimates in the 10-6range.

Post-application: All registered dust/powder and pump/trigger spray products result in 

residential post-application cancer aggregate (residential and dietary) risk estimates in the 

10-6range. Assuming liquid formulation of pet collars, aggregate risk estimates are in the 

10-6range using the amitraz study and are in the 10-5to 10-6range when using the Davis 

study. For the dust collar assumption, only the amitraz data were used and those cancer 

aggregate risk estimates are in the 10-5 range (cancer aggregate risk estimate values would

be lower if using the Davis data).

Occupational Risk Assessment

Non-cancer (steady state) and cancer exposures and risks were calculated for occupational 

handlers of TCVP for all registered uses. Generic, surrogate handler data were used except in 

the case of a WP high pressure hand wand scenario; that scenario used chemical specific data in 

addition to the generic data.

Steady state inhalation exposure and risk estimates were calculated for occupational handlers of 

TCVP for a variety of exposure scenarios at differing levels of respiratory personal protection 

including engineering controls. Steady state dermal exposures were not quantitatively assessed 

as there is no non-cancer dermal hazard. 

Of the 172 total occupational handler exposure scenarios assessed, the majority (152) are not of 

concern (i.e., steady state inhalation MOEs are ≥ 300) with currently required personal protective 

equipment (PPE) (i.e., respiratory protection). Of the remaining 20 handler exposure scenarios, 

an additional 16 are not of concern with consideration of increasing levels of respiratory 

protection (i.e., four occupational handler exposure scenarios result in estimated risks of concern 

despite the addition of respiratory protection or engineering controls). These four handler 

scenarios are all dust formulations (mixing/loading/applying TCVP by rotary duster, self-treating 

dust bag, or shaker can).

Occupational cancer (combined inhalation and dermal) risks were estimated for both 

private/farmer and contract/commercial handlers. Cancer risks range from 10-10 to 10-5for 

private/farmer handlers and from 10-10 to 10-4for contract/commercial handlers with currently 

required PPE. 

Occupational post-application exposures are not expected as reentry activities are not anticipated 

for the registered TCVP uses. There are no risk concerns for occupational post-application 

exposures to TCVP.
Page 11 of 152

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 studies from 

PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; the ARTF database; the Residential SOPs (Treated Pets); as well as a TCVP 

dust/powder applicator exposure study (MRID 45519601), and TCVP dust and pump spray study 

(MRID 45485501) and an amitraz pet collar residue transfer study (MRID 49468801) (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 (HSRB). Descriptions of data sources, as well as 

guidance on their use, can be found at the agency website5. 

Data were also used from a literature study using TCVP pet collars (Davis, M. et. al., 2008). That 

study has undergone internal EPA science and ethics review and will also undergo review by the 

HSRB (the next scheduled HSRB meeting is January 2016).

2.0 HED Recommendations

2.1 Data Deficiencies

None. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

A gas liquid chromatography (GLC) method for the determination of TCVP per se in livestock

commodities is described in the Pesticide Analytical Method (PAM), Vol. II, as Method I. 

The registrant has submitted a method (14020.6106) for the determination of tetrachlorvinphos 

and its metabolites (TCVPdeme, TCPEdiol, TCPEone and TCPEol) in livestock commodities, 

which uses QuEChERS and LC/MS/MS methods. The test data for method 14020.6106 are 

classified as scientifically acceptable for use as an analytical method for ruminant and poultry 

commodities.

The submitted multiresidue method testing data are acceptable and indicate that FDA 

multiresidue methods are not suitable for analysis of the TCVP metabolites TCPEdiol and 

TCVPdeme. However, the metabolites TCPEol and TCPEone were recoverable under Protocol 

F, although fortified recoveries were small (<50%).

It should be noted that the FDA PESTDATA database dated 8/93 (PAM Vol. I, Appendix II) 

indicates that parent compound TCVP is completely recovered (>80%) using FDA multiresidue 

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 12 of 152

method protocol D (section 232.4) but is not recovered using protocol E (Sections 211.1/231.1 

and 212.1/232.1, fatty and nonfatty matrices). 

2.2.2 International Harmonization

There are no Codex maximum residue limits (MRLs) established or proposed for residues of 

TCVP. Canada has established MRLs for plant (apple and grape) and livestock commodities. 

The U.S. tolerances are for livestock commodities; there are no registered crop uses. Canada’s 

residue definition is 2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl phosphate (TCVP) and its 

low melting isomer as opposed to the U.S. definition which includes the parent compound TCVP 

plus the four metabolites of concern. The differences in U.S. and Canadian residue definitions

prohibit harmonization. HED has not examined the Canadian registrations; different use patterns 

may also be a factor in achieving harmonization. A summary of U.S. and international 

tolerances and maximum residue limits is presented in Appendix E.

2.2.3 Recommended Tolerances

Tolerances for residues of TCVP are established under 40 CFR §180.252. The current tolerance 

expression is for the combined residues of tetrachlorvinphos [(Z)-2-chloro-1-(2,4,5-

trichlorophenyl)vinyl dimethyl phosphate] and its metabolites, 1-(2,4,5-trichlorophenyl)-ethanol 

(free and conjugated forms), 2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)-

ethanediol. 

Time limited TCVP tolerances are established for the animal commodities under 40 CFR 

§180.252 and were based on the available metabolism data. In the 2006 RED (USEPA, July 

2006, Reregistration Eligibility Decision (RED)), time-limited tolerances were recommended to 

allow time for the registrant to submit new magnitude of residue studies. Sufficient residue data 

have been submitted in order to determine the appropriate tolerances for residues of TCVP on 

livestock commodities. 

The HED Metabolism Committee has determined that the residues of concern for tolerance 

enforcement are tetrachlorvinphos, des-O-methyl tetrachlorvinphos, 1-(2,4,5-

trichlorophenyl)ethanol (free and conjugated forms), 2,4,5-trichloroacetophenone, and 1-(2,4,5-

trichlorophenyl)ethanediol. The current tolerance expression under 40 CFR §180.252 includes 

all of these residues except des-O-methyl tetrachlorvinphos; this metabolite should be included in 

the tolerance expression. To allow separate risk assessments for 1) cholinesterase inhibition 

(parent TCVP only) and 2) carcinogenicity (parent plus metabolites), the tolerances for each 

livestock commodity also specify the maximum residues of TCVP per se from the total residues. 

The tolerance definition should be modified as follows, to be consistent with the Tolerance 

Expression Guidance issued 5/27/09 (S. Knizner).

Tolerances are established for residues of the insecticide tetrachlorvinphos, 

including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined 

by measuring only the sum of tetrachlorvinphos [(Z)-2-chloro-1-(2,4,5-

trichlorophenyl)vinyl dimethyl phosphate) and its metabolites chloro- 1 -(2,4,5-
Page 13 of 152

trichlorophenyl)-vinylmonomethyl phosphate, 1-(2,4,5-trichlorophenyl)-ethanol 

(free and conjugated forms), 2,4,5-trichloroacetophenone, and 1-(2,4,5-

trichlorophenyl)-ethanediol, calculated as the stoichiometric equivalent of 

tetrachlorvinphos, in or on the commodity.

Table 2.2.3. Tolerance Reassessment Summary for Tetrachlorvinphos.

Commodity Established

Tolerance 1

(ppm)

Maximum Residues 2

(ppm)

Reassessed 

Tolerance 

3,4

(ppm)

Comments;

Correct Commodity 

Definition

Cattle, fat (of which no 

more than 0.1 ppm is 

tetrachlorvinphos per se)

0.2 0.84 (0.56) subcutaneous 

fat;

0.75 (0.34) peritoneal fat

1.0 Cattle, fat (of which no more 

than 0.6 ppm is 

tetrachlorvinphos per se)

Cattle, kidney (of which 

no more than 0.05 ppm is 

tetrachlorvinphos per se)

1.0 -- Remove

See cattle, meat byproducts

Cattle, liver (of which no 

more than 0.05 ppm is 

tetrachlorvinphos per se)

0.5 -- Remove

Cattle, meat (of which no 

more than 2.0 ppm is 

tetrachlorvinphos per se)

2.0 0.27 (0.21) muscle 0.3 Cattle, meat (of which no 

more than 0.2 ppm is 

tetrachlorvinphos per se)

Cattle, meat by products, 

except kidney and liver

1.0 -- Remove See cattle, meat byproducts

Cattle, meat by products None 0.16 (<0.01) liver;

0.28 (0.015) kidney;

0.84 (0.56) subcutaneous 

fat;

0.75 (0.34) peritoneal fat;

0.27 (0.21) muscle

1.0 Cattle, meat byproducts (of 

which no more than 0.6 ppm 

is tetrachlorvinphos per se) 5

Egg (of which no more 

than 0.05 ppm is 

tetrachlorvinphos per se)

0.2 0.288 (0.026) 0.3 Egg (of which no more than 

0.03 ppm is tetrachlorvinphos 

per se)

Hog, fat (of which no 

more than 0.1 ppm is 

tetrachlorvinphos per se)

0.2 0.84 (0.56) subcutaneous 

fat;

0.75 (0.34) peritoneal fat

1.0 Hog, fat (of which no more 

than 0.6 ppm is 

tetrachlorvinphos per se)

Hog, kidney (of which no 

more than 0.05 ppm is 

tetrachlorvinphos per se)

1.0 -- Remove See hog, meat byproducts

Hog, liver (of which no 

more than 0.05 ppm is 

tetrachlorvinphos per se)

0.5 -- Remove

Hog, meat (of which no 

more than 2.0 ppm is 

tetrachlorvinphos per se)

2.0 0.27 (0.21) muscle 0.3 Hog, meat (of which no more 

than 0.2 ppm is 

tetrachlorvinphos per se)

Hog, meat byproducts, 

except kidney and liver

1.0 -- Remove See hog, meat byproducts
Page 14 of 152

Table 2.2.3. Tolerance Reassessment Summary for Tetrachlorvinphos.

Commodity Established

Tolerance 1

(ppm)

Maximum Residues 2

(ppm)

Reassessed 

Tolerance 

3,4

(ppm)

Comments;

Correct Commodity 

Definition

Hog, meat by products None 0.16 (<0.01) liver;

0.28 (0.015) kidney;

0.84 (0.56) subcutaneous 

fat;

0.75 (0.34) peritoneal fat;

0.27 (0.21) muscle

1.0 Hog, meat byproducts (of 

which no more than 0.6 ppm 

is tetrachlorvinphos per se) 5

Milk, fat (reflecting 

negligible residues in 

whole milk and of which 

no more than 0.05 ppm is 

tetrachlorvinphos per se)

0.05 0.072 (0.036) for milk;

0.078 (<0.01) for cream

0.1 Milk (of which no more than 

0.04 ppm is tetrachlorvinphos 

per se)

Poultry, fat (of which no 

more than 7.0 ppm is 

tetrachlorvinphos per se)

7.0 1.298 (0.099) abdominal 

fat

1.4 Poultry, fat (of which no 

more than 0.1 ppm is 

tetrachlorvinphos per se)

Poultry, liver (of which no 

more than 0.05 ppm is 

tetrachlorvinphos per se)

2.0 Remove See poultry, meat byproducts

Poultry, meat (of which no 

more than 3.0 ppm is 

tetrachlorvinphos per se)

3.0 0.40 (0.082) muscle 0.4 Poultry, meat (of which no 

more than 0.1 ppm is 

tetrachlorvinphos per se)

Poultry, meat byproducts, 

except liver

2.0 -- Remove See poultry, meat byproducts

Poultry, meat byproducts None 0.52 (0.016) liver;

0.58 (0.022)

kidney;

0.40 (0.082) muscle;

19.41 (6.03) skin with fat;

1.30 (0.099) abdominal 

fat

20 Poultry, meat byproducts (of 

which no more than 6.0 ppm 

is tetrachlorvinphos per se) 5

1

 Time-limited tolerances; current tolerance expression is for the combined residues of tetrachlorvinphos [(Z)-2-chloro-1-(2,4,5-

trichlorophenyl)vinyl dimethyl phosphate] and its metabolites, 1-(2,4,5-trichlorophenyl)-ethanol (free and conjugated forms), 

2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)-ethanediol; expression should also include des-O-methyl 

tetrachlorvinphos.

2

 Total residues of tetrachlorvinphos and its metabolites, TCVP-deme, TCPEone, TCPEol (free and conjugated forms), and 

TCPEdiol (free and conjugated), expressed in terms of parent equivalents; the value in parentheses represents the maximum 

residues of the parent tetrachlorvinphos.

3

 Reassessed tolerance is based on the maximum residue from the respective magnitude of the residue study; the maximum 

residues of the parent tetrachlorvinphos are reported in the corrected commodity definition.

4 The residue data for cattle can be used to set tolerances for hog commodities since residues in hog tissues are not likely to be 

greater than those in cattle tissues.

5 According to the 18 July 2007 Minutes of the HED ChemSAC meeting, the guidance document will be revised to include 

language detailing the use of the highest residue data for any tissue (liver, kidney, fat, skin or muscle) to determine the tolerance 

for meat byproducts. A single tolerance on “meat byproducts” will be recommended based on that highest residue, and 

individual tolerances will no longer be set on liver, kidney, or meat byproducts (except liver and kidney).
Page 15 of 152

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The following label revisions are recommended based on the application methods and rates used 

in the tetrachlorvinphos magnitude of the residue studies, which were used to determine the 

appropriate tolerance levels in livestock commodities (GLN 860.1200 Directions for Use):

• Based on the magnitude of the residue study on cattle, the product labels with direct 

animal spray uses on cattle (EPA Reg. Nos. 61483-43 and 61483-50) should be amended 

to specify a maximum of three applications, with two-week retreatment intervals, at 19 g 

ai/animal/dose. The product label for Ravap (EPA Reg. No. 61483-50) should also be 

amended to provide conversion factors to allow calculation of direct animal spray 

treatment rate in terms of g ai/animal. 

• Based on the magnitude of the residue study on poultry, the product labels with direct 

animal spray uses on poultry (EPA Reg. Nos. 61483-43 and 61483-50) should be 

amended to specify a maximum of seven applications (with two-week retreatment 

intervals) at 0.18 g ai/hen/application. Note that the label should specify the weight or 

volume of the product to be applied.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Tetrachlorvinphos Nomenclature.

Compound

P

O

O

H3CO

OCH3

Cl

Cl Cl

Cl

Common name Tetrachlorvinphos

Company experimental name TCVP

IUPAC name (Z)-2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl phosphate

CAS registry number 22248-79-9

End-use products registered to 

KMG Bernuth, Inc.

Rabon 50 WP Insecticide (EPA Reg. No. 61483-43, 50% WP);

Rabon 3% Insecticide Dust EPA Reg. No. 61483-45, 3% D); 

Rabon 97.3 Oral Larvicide (EPA Reg. No. 61483-47, 97.3% G); 

Rabon 7.76 Oral Larvicide Premix (EPA Reg. No. 61483-48, 7.76% G); and

Ravap EC Livestock, Poultry & Premise Insecticide Spray (EPA Reg. No. 61483-50, 23% 

EC)

See Appendices C and D for nomenclature and physical/chemical properties of TCVP and 

metabolites (TCVPdeme, TCPEdiol, TCPEone and TCPEol, TCCEol, TCBA).
Page 16 of 152

3.2 Physical/Chemical Characteristics

Technical tetrachlorvinphos is a tan to brown crystalline solid with a melting point of 93-98 °C. 

TCVP is not expected to volatilize significantly due to a low vapor pressure of 2.6 x 10-7torr 

(25°C). The solubility of tetrachlorvinphos in water at 25°C is 11.6 mg/L. TCVP has limited 

solubility in most aromatic hydrocarbons. TCVP is hydrophobic, with an octanol-water partition 

coefficient of 3350 (Log Kow of 3.53).

3.3 Pesticide Use Pattern

TCVP is used as a direct animal treatment to livestock (i.e., cattle, horses, poultry and swine) and 

their premises, in kennels, outdoors as a perimeter treatment, and as a flea treatment on cats and 

dogs. There are 42 end-use product labels currently registered with TCVP as the active 

ingredient (ai). The TCVP livestock and perimeter treatment uses are formulated as follows: 

dusts (D), emulsifiable concentrates (EC), feed through (solid and liquid food additives), feed 

blocks, and wettable powders (WP). TCVP can be applied by a variety of means/equipment 

types including: backrubber/facerubber; backpack; cup; groundboom; handheld fogger; 

manually-pressurized handwand; mechanically-pressurized handwand; open pour (dust and 

liquid formulations); paint (airless sprayer or brush/roller); pet collar; plunger; rotary duster; 

shaker can; spoon; stationary fogger; and trigger spray. For a complete list of registered uses, 

including maximum use rates, see Appendix L of this document.

3.4 Anticipated Exposure Pathways

Humans may be exposed to TCVP residues in food since TCVP may be directly applied to, or 

fed to, livestock which may result in residues in animal commodities. TCVP may reach surface 

and ground water sources of drinking water through the outdoor usage on poultry droppings, 

garbage and manure piles, and kennels and corrals. Residential exposures (handler and postapplication) may occur as a result of the application to dogs and cats as dust/powders, sprays, or 

collars. In an occupational setting, applicators may be exposed while handling the pesticide prior 

to application, as well as during application. Occupational post-application exposures are not 

expected as reentry activities are not anticipated for the registered TCVP uses.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf. 

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under the National Health and Nutrition Survey/What We Eat in America 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a
Page 17 of 152

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 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. 

Figure 1. Adverse outcome pathway for OPs

4.1 Toxicology Studies Available for Analysis

The toxicology database for TCVP is complete for risk assessment. There are acceptable studies 

available for toxicity endpoint selection; they include: 

 subchronic oral toxicity studies in rats 

 chronic oral toxicity studies in rats and dogs 

 carcinogenicity studies in rats and mice 

 developmental studies in rats and rabbits 

 reproduction study in rats 

 acute and subchronic neurotoxicity studies in rats

 developmental neurotoxicity (DNT) study in rats 

 acute and repeated comparative (CCA) cholinesterase (ChE) studies in juvenile 

and adult rats

 repeated, gestational ChE study in pregnant rat and fetuses

 delayed neurotoxicity study in hens 

 subchronic dermal toxicity study in rats 

Target 

Tissue Dose

Phosphorylation 

of the active site 

of AChE

Neurotoxicity Accumulation of 

acetylcholine
Page 18 of 152

 repeated dosing inhalation toxicity study in rats

 immunotoxicity study in mice 

 complete mutagenicity study battery 

 metabolism study in rats 

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)

TCVP, unlike some other OPs, does not require metabolic activation to the oxon metabolite to 

inhibit AChE. In a rat metabolism study, TCVP was almost completely metabolized, and most of 

the radiolabel was excreted in the urine (46%-60%) and feces (38%-56%) within 48 hours of 

dosing. Only minor amounts (>0.5%) were found in the tissues. Very little un-metabolized parent 

compound was recovered. The major metabolite in feces was trichlorophenylethanol, with lesser 

amounts of trichlorophenylethandiol. The major metabolite in urine was trichloromandelic acid, 

with lesser amounts of desmethyl tetrachlorvinphos. There is no evidence of bioaccumulation. 

Some differences in metabolism were noted between the sexes; e.g., males excreted more 

trichloromandelic acid, a more completely metabolized form of TCVP, whereas females excreted 

more of the desmethyl TCVP, which could be derived from TCVP with only a single metabolic 

step. 

4.2.1 Dermal Absorption

A dermal absorption factor (DAF) of 9.6% was used to evaluate dermal exposures in the cancer 

risk assessment. Since there was no dermal hazard identified for non-cancer endpoints, a 

quantitative dermal assessment was not performed (see Section 4.6.1).

4.3 Toxicological Effects

AChE inhibition is the well-established cholinergic mode of action for OPs and is typically used 

as the critical effect in hazard characterization for members of this class of pesticides. TCVP 

inhibits cholinesterase activity in various species including rats, mice, rabbits, and dogs. TCVP 

has cholinesterase data across multiple lifestages, durations, and routes for both red blood cell 

(RBC) and brain cholinesterase inhibition. Cholinesterase inhibition is the most sensitive effect 

for TCVP, however, TCVP data demonstrate a shallow dose-response curve for AChE inhibition 

across many of the studies in the database resulting in varying magnitudes of response across the 

database. Large increases in administered dose result in only small changes in AChE inhibition. 

For example, in the 11-day repeat adult CCA study, 5 mg/kg and 10 mg/kg resulted in about 

10% RBC inhibition, 50 mg/kg from 30-40% RBC inhibition, and 200 mg/kg only 40-60% 

inhibition. A similar response was observed in brain AChE with no inhibition at 5 mg/kg, 7-12% 

at 10 mg/kg, 15-40% at 50 mg/kg, and only 18-57% at 200 mg/kg. In the 21-day repeat toxicity 

study, 20 mg/kg resulted in approximately 30% RBC inhibition while the highest dose of 50 

mg/kg resulted in only 30-40% inhibition. 

Many of the toxicological studies for TCVP have been considered for benchmark dose (BMD) 

modeling (Bever/Holman; 5/20/14; TXR# 0056970 and Appendix B). However, a number of 

datasets were not amenable to BMD modeling due to the shallow dose response described above. 

Some studies in the database, however, were amenable to BMD modeling and provided a robust 
Page 19 of 152

evaluation of the RBC and brain AChE activity. In general, RBC and brain cholinesterase 

inhibition were similarly inhibited across the database. It should be noted that is some cases RBC 

data provided a more robust dose-response and, therefore, more reliable BMD estimates. Male 

and female adult rats were also generally affected similarly across the various studies; although 

sporadically, one sex appears more sensitive; there is no consistent pattern. For example, in the 

repeat oral subchronic study, adult females were more sensitive (RBC and brain) than adult males, 

while in the single dose study (MRID 45570601), males were more sensitive (brain) than adult 

females. High quality AChE data for the dermal and inhalation routes are also available and allow 

for route specific evaluation. RBC AChE inhibition was observed in both sexes in the inhalation 

study (brain AChE was not assessed), while no inhibition of RBC or brain AChE was observed in 

the dermal study up to the limit dose. 

Transient clinical signs [gait alterations, constricted pupils, tremors (fore- and hindlimb), body 

cool to the touch, decreased defecation, red material on forelimbs, around eyes, nose, mouth]

characteristic of cholinergic toxicity were observed at the high dose (650 mg/kg) in the acute 

neurotoxicity rat study, and tremors were observed in pregnant rats in the developmental toxicity 

study at dose levels 5X higher than those eliciting AChE inhibition.

There is no evidence of quantitative or qualitative sensitivity in the developmental rat and rabbit 

study or in the gestational (fetus) or juvenile (PND11) components of the CCA study. In the acute 

and repeated comparative cholinesterase assays, juvenile rats (PND 11 and PND 21), pregnant 

dams, fetuses, and non-pregnant females show similar results in both RBC and brain AChE 

activity. At the lowest tested dose of 75 mg/kg/day in the acute CCA study, there was little 

difference in RBC or brain AChE inhibition between the PND11, PND21, or young adult 

(PND42). Similarly, the PND11 and PND21 rats in the CCA study are similarly sensitive as adult 

rats exposed to a single dose of 50 mg/kg from a separate peak inhibition study. The repeat dosing 

phase of the CCA also demonstrates the lack of sensitivity in AChE inhibition in the juvenile 

(PND11) rats. Furthermore, the fetus is not more sensitive than the pregnant dam. Therefore, 

points of departure that are based on adult AChE data are also protective of the postnatal and 

gestational lifestages. 

In the rat developmental toxicity study, no developmental effects were observed in the fetus at 

dose levels where minimal effects (decreased body weight gains) were observed in the dams. 

Developmental toxicity (increased early resorptions, post-implantation loss, and decreased number 

of live fetuses) was observed in the rabbit developmental toxicity study at the same dose level 

where significant toxicity (mortality, abortion) was observed in the maternal rabbit. No 

reproductive or offspring toxicity was observed in the 2-generation reproductive rat study, but 

increased adrenal weights were observed in the parental rats.

In the developmental neurotoxicity study (DNT), quantitative susceptibility was only observed in 

pups (decreased pup weight, decreased relative brain weight/measurements) at the high dose of 

200 mg/kg/day. However, a 200 mg/kg/day dose to juvenile rats is 10-fold higher than doses 

reflecting approximately 10% inhibition in juvenile pups in the CCA study and 25-fold higher than 

the point of departure. Therefore, when considered in combination with the results from the CCA, 

sensitivity occurring at doses relevant for risk assessment was not observed in the database. Thus, 
Page 20 of 152

data from adult animals are protective of any effects in the young. Additionally, BMD results using 

cholinesterase inhibition are protective for the effects observed in pups in the DNT study. 

TCVP is classified as a Group C possible human carcinogen with a linear low-dose approach for 

quantification of risk using the oral slope factor (Q1*) of 1.83 x 10-3. 

In acute lethality studies, 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. 

4.3.2 Critical Durations of Exposure

One of the key elements in risk assessment is the appropriate integration of temporality between 

the exposure and hazard assessments. One advantage of an AOP understanding is that human 

health risk assessments can be refined and focused on the most relevant durations of exposure. 

The following text provides an analysis of the temporal pattern of AChE inhibition from repeated 

dosing studies in laboratory animals for TCVP. This analysis provides the basis for determining 

which exposure durations are appropriate for assessing the human health risk. Table 4.3.2.1 

provides a summary of the representative results from experimental toxicology studies with TCVP 

for female adult rats. 

Table 4.3.2.1. TCVP BMD10 Results (mg/kg/day) for RBC and Brain AChE Inhibition Over Time 

in Female Adult Rats 

MRID (study) Days of Dosing

% inhibition at LOAEL 

(mg/kg) or the BMD10 

1

RBC

MRID 45570601 (single dose) 1 day 37% at 50

MRID 48773401 (repeat CCA) 11 days 10% at 8.7 (BMD10)

MRID 45570601 (21-day oral) 21 days 10% at 9.9 (BMD10)

MRID 43371201 (90-day oral) 90 days 10% at 10.5 (BMD10)

MRID 42980901 (chronic oral) 365 days 29% at 63

Brain

MRID 45570601 (single dose) 1 day 23% at 50

MRID 48294601 (acute CCA) 1 day 10% at 11.3 (BMD10)

MRID 48773401 (repeat CCA) 11 days 10% at 7.2 (BMD10)

MRID 45570601 (21-day oral) 21 days 10% at 14.7 (BMD10)

MRID 43371201 (90-day oral) 90 days 12% at 6.7

MRID 42980901 (chronic oral) 365 days 14% at 63

 1The BMD, not the BMDL, estimates are shown when available in Table 4.3.2.1. According to the BMD guidance, the central 

estimate (i.e., the BMD) is used for purposes of comparison. The LOAEL and percent inhibition is presented when a BMD estimate 

is not available.
Page 21 of 152

In adults, OPs generally exhibit a phenomenon known as steady state cholinesterase inhibition. 

After repeated dosing at the same dose, 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. This pattern is observed for most OPs, but not every OP, like TCVP, 

which shows no difference in response across duration. 

In the specific case for TCVP, this OP exhibits a shallow dose-response curve for cholinesterase 

inhibition and little change in response across duration. In other words, large increases in 

administered dose result in only small changes in AChE inhibition, and increasing duration does 

not result in more inhibition as is typical for most OPs. 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 BMD10 / 3.6 to 26.3 mg/kg/day BMDL10 (Appendix B). Moreover, when 

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

different studies at comparable dose levels. 

A single dose rat study (MRID 45570601) resulted in no RBC or brain AChE inhibition at 8 

mg/kg while in males 12 mg/kg resulted in 29% RBC inhibition and only 46% at 50 mg/kg; in 

other words in the single dose adult rat study, a 4-fold dose spread led to only 16% increased 

response. Similarly, the acute CCA study (MRID 48294601) shows a shallow dose response: 75 

mg/kg resulted in 14-35% RBC inhibition with 15-35% inhibition at 150 mg/kg and 20-47% at 

300 mg/kg. Similar RBC AChE inhibition was observed from these two acute studies and across 

the 12 mg/kg to 300 mg/kg combined dose range. 

In the chronic rat toxicity study, increasing the dose 2-fold only leads to changes in female RBC 

AChE inhibition of less than 10%. In the same study at a dose of 125 mg/kg/day, females 

displayed 17-25% RBC AChE inhibition, whereas males displayed no RBC AChE inhibition at 

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

AChE inhibition at a dose of 75 mg/kg/day, whereas in the 21-day subchronic oral study, nonpregnant female rats showed approximately 40% RBC AChE inhibition at a dose of 50 

mg/kg/day. 

All of these studies support the shallow dose-response across 10-fold or greater doses as well as 

the lack of increased inhibition with repeat exposure. For example, the single dose study in 

adults demonstrates a NOAEL of 8 mg/kg for both brain and RBC AChE; the RBC BMDL10

from the 90-day subchronic toxicity rat study being used as the POD is 8 mg/kg/day. A single 

dose of 50 to 75 mg/kg resulted in 14- 46% RBC AChE while in the 11-day repeat CCA study a 

dose of 75 mg/kg/day resulted in similar RBC AChE inhibition of 13-40%. The 21-day toxicity 

study (MRID 45570601) evaluated doses of 8, 12, 20 and 50, which resulted in RBC NOAELs 

of 8 mg/kg/day after 21 days and NOAEL of 12 mg/kg/day in females for brain AChE. No RBC 

inhibition was observed at 6 mg/kg/day in the 90-day toxicity study while RBC was 30-80% 

inhibited at 142 mg/kg/day. The chronic toxicity study also demonstrated lack of RBC AChE 

inhibition at 5.9 mg/kg/day and approximately 30% RBC AChE inhibition at 63 mg/kg/day. 

Therefore, the lack of inhibition at 6 and 8 mg/kg/day across the acute and repeat dosing studies 

suggests the lack of increased inhibition with duration.
Page 22 of 152

Although the durations of the toxicity and exposure assessments may differ among the OPs, an 

exact match is not necessary and would suggest a level of precision that the toxicity data do not 

support. Given this, the 21-day and longer exposure assessment is scientifically supportable and 

also provides consistency with the OP cumulative risk assessment (OP Cumulative Risk 

Assessment (CRA); 2002, 2006) and across the single chemical risk assessment for the OPs. As 

such, the single chemical OP assessments will evaluate steady state (a 21-day assessment) 

instead of the typical chronic duration dietary assessment. The steady state point of departure is 

protective of any exposure duration longer than 21-days, including chronic exposure, since 

cholinesterase inhibition does not increase after reaching maximum inhibition or steady state.

4.4 Literature Review on Neurodevelopment Effects

For the OPs, historically the agency has used inhibition of AChE as the POD for human health 

risk assessment; at present time, this policy continues. This science policy is based on decades 

of work which shows that AChE inhibition is the initial event in the pathway to acute cholinergic 

neurotoxicity. The use of AChE inhibition data for deriving PODs was supported by the FIFRA 

SAP (2008, 2012) for chlorpyrifos as the most robust source of dose-response data for 

extrapolating risk and is the source of data for PODs for TCVP. A detailed review of the 

epidemiological studies used in this review can be found either in the 2014 chlorpyrifos revised 

draft human health risk assessment ((D424485, D. Drew et al., 12/29/2014) or in the 2015 

literature review for other organophosphates (OPP/USEPA; D331251; 9/15/15). 

Newer lines of research on OPs in the areas of potential AOPs, in vivo animal studies, and 

notably epidemiological studies in mothers and children, have raised some uncertainty about the 

agency’s risk assessment approach with regard to the potential for neurodevelopmental effects in 

fetuses and children. Many of these studies have been the subject of review by the agency over 

the last several years as part of efforts to develop a risk assessment for chlorpyrifos (D424485, 

D. Drew et al., 12/29/2014). Initially, the agency focused on studies from three US cohorts: 1) 

The Mothers and Newborn Study of North Manhattan and South Bronx performed by the 

Columbia Children’s Center for Environmental Health (CCCEH) at Columbia University; 2) the 

Mt. Sinai Inner-City Toxicants, Child Growth and Development Study or the “Mt. Sinai Child 

Growth and Development Study;” and 3) the Center for Health Assessment of Mothers and 

Children of Salinas Valley (CHAMACOS) conducted by researchers at University of California 

Berkeley. The agency has evaluated these studies and sought external peer review (FIFRA SAP 

reviews in 2008 and 2012; federal panel, 20136) and concludes they are of high quality. In the 

three US epidemiology cohort studies, mother-infant pairs were recruited for the purpose of 

studying the potential health effects of environmental exposures during pregnancy on subsequent 

child development. Each of these cohorts evaluated the association between prenatal chlorpyrifos 

and/or OP exposure (with adverse neurodevelopmental outcomes in children through age 7 

years. For the 2014 chlorpyrifos revised human health risk assessment (D424485, D. Drew et 

al., 12/29/2014), EPA included epidemiologic research results from these three US prospective 

birth cohort studies but primarily focused on the results of CCCEH since this cohort has 

published studies on the association between cord blood levels of chlorpyrifos and 

 

6 http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0850-0170
Page 23 of 152

neurodevelopmental outcomes. The agency retained the FQPA 10X Safety Factor (SF) in the 

2014 chlorpyrifos revised risk assessment, in large part, based on the findings of these studies.

In the 2015 updated literature review (OPP/USEPA; D331251; 9/15/15), the agency conducted a 

systematic review expanding the scope of the 2012/2014 review focused on US cohort studies 

with particular emphasis on chlorpyrifos. The expanded 2015 review includes consideration of 

the epidemiological data on any OP pesticide, study designs beyond prospective cohort studies, 

and non-U.S. based studies. The updated literature review identified seven studies which were 

relevant (Bouchard et al., 2010; Fortenberry et al., 2014; Furlong et al., 2014; Guodong et al., 

2012; Oulhote and Bouchard, 2013; Zhang et al., 2014; Shelton et al., 2014). These seven 

studies have been evaluated in context with studies from the 2012/2014 review (D424485, D. 

Drew et al., 12/29/2014). Only a brief summary is provided below.

The OP exposure being assessed in many of these studies used concentrations of urinary dialkyl 

phosphate metabolites (DAPs) as the urinary biomarker. Total DAPs is a non-specific measure 

of OP exposure and is the sum of six separate molecules - three dimethyl alkylphosphate 

(DMAP) molecules of DMP, DMTP, DMDTP, and three diethyl alkylphosphate (DEAP) 

molecules of DEP, DETP, and DEDTP. Each metabolite is a breakdown product from multiple 

OPs (Table 4.4.-1; CDC, 2008)7. Specifically, DMP, DMTP, and DMDTP are associated with 

18, 13, and 5 OPs, whereas DEP, DETP, and DEDTP are associated with 10, 10, and 4 OPs, 

respectively. Thus, using urinary DAPs alone as an exposure measure, it is not possible to 

separate the exposure and associated effects for single, specific OPs. 

Table 4.4.1. CDC Table of organophosphate pesticides and their dialkyl phosphate metabolites (2008)

Pesticide DMP DMTP DMDTP DEP DETP DEDTP

Azinphos methyl X X X

Chlorethoxyphos X X

Chlorpyrifos X X

Chlorpyrifos methyl X X

Coumaphos X X

Dichlorvos (DDVP) X

Diazinon X X

Dicrotophos X

Dimethoate X X X

Disulfoton X X X

Ethion X X X

Fenitrothion X X

Fenthion X X

Isazaphos-methyl X X

Malathion X X X

Methidathion X X X

Methyl parathion X X

Naled X

Oxydemeton-methyl X X

 

7 http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/l26opd_c_met_organophosphorus_pesticides.pdf
Page 24 of 152

Parathion X X

Phorate X X X

Phosmet X X X

Pirimiphos-methyl X X

Sulfotepp X X

Temephos X X

Terbufos X X X

Tetrachlorvinphos X

Trichlorfon X

DMP = dimethylphosphate; DEP = diethylphosphate; DMTP = dimethylthiophosphate; DMDTP = 

dimethyldithiophosphate; DETP = diethylthiophosphate; DEDTP = diethyldithiophosphate.

For studies which measured urinary 3,5,6-trichloro-2-pyridinol (TCPy) (e.g., Fortenberry et al., 

2014; Eskenazi et al., 2007; Whyatt et al., 2009), this metabolite can be derived from 

chlorpyrifos, chlorpyrifos-methyl, and the herbicide triclopyr. TCPy is also the primary 

environmental degradate of chlorpyrifos, chlorpyrifos-methyl, and triclopyr; thus exposure can 

be found directly on food treated with these pesticides. CCCEH studies have largely used 

chlorpyrifos measured in cord blood as the specific biomarker (e.g., Lovasi et al., 2010; Whyatt 

et al., 2004; Rauh et al., 2011). The CHARGE study (Shelton et al., 2015) did not measure 

biomarkers but instead used geospatial analysis to focus on the residential proximity to OP 

exposure using data from the California Department of Pesticide Regulation, with five OPs 

accounting for a total of 73% of the pesticide applied near residential settings (chlorpyrifos, 

acephate, diazinon, bensulide, and dimethoate). 

Similarly, DAPs can be found directly on food following OP applications (Zhang et al., 2008; 

Chen et al., 2012). Specifically, studies have shown that DAPs may form as environmental 

degradates from abiotic hydrolysis, photolysis, and plant metabolism (Zhang et al., 2008; Chen 

et al., 2012; Racke et al., 1994). Furthermore, since these DAPs are excreted more rapidly and 

extensively than the parent OPs (Zhang et al., 2008; Forsberg et al., 2008), direct exposure to 

DAPs may lead to an overestimate of OP exposure when using urinary DAPs as a biomarker of 

OP exposure. The agency recognizes that this is a source of uncertainty when using DAPs for 

assessing OP exposure and will continue to monitor this issue in future assessments. 

With respect to neurological effects near birth, the CHAMACOS and Mt. Sinai cohorts measured 

neurological effects at birth, and observed a putative association with total DEAP, total DMAP, 

and total DAP exposure (Engel et al., 2007; Young et al., 2005). Similarly, a Chinese study 

(Zhang et al., 2014) reported statistically significant associations between for total DEAPs, total 

DMAPs, and total DAPs from prenatal OP pesticide exposure and neonatal neurodevelopment 

assessed 3 days after birth. However, another cross-sectional Chinese study, Guodong et al. 

(2012), observed no association with urinary DAPs and a developmental quotient score for 23-25 

month old children.

The 3 US cohorts (CCCEH, Mt. Sinai, CHAMACOS) each reported evidence of impaired mental 

and psychomotor development, albeit not consistent by age at time of testing (ranging from 6 

month to 36 months across the three cohorts). Attentional problems and ADHD were reported 

by three prospective cohorts [Rauh et al., 2006; Eskenazi et al., 2007; Marks et al., 2010; and 

Fortenberry et al. (2014)] investigators with additional support from a case control study, 
Page 25 of 152

Bouchard et al. (2010). The exposure metric varied among these studies. Specifically, 

Fortenberry et al. (2014) found suggestive evidence of an association with TCPy and ADHD in 

boys, whereas statistically significant associations were observed by Rauh et al. (2006) with chlorpyrifos 

exposure and ADHD. Eskenazi et al. (2007) reported associations with total DMAPs and total DAPs and 

ADHD; Marks et al. (2010) reported associations with total DEAP, DMAP, and total DAP exposure 

and ADHD. In a national cross-sectional study of Canadian children, using 2007-2009 data for 

children age 6-11 years (Oulhote and Bouchard, 2013), there were no overall statistically 

significant associations observed between child urinary DEAP, DMAP, or total DAP metabolite 

levels and parentally reported behavioral problems. In contrast, Bouchard et al. (2010), looking 

at U.S. children age 8-15 years in the 2000-2004 National Health and Nutrition Examination 

Survey (NHANES), observed a positive association between attention and behavior problems 

and total DAPs and DMAPs, but not DEAPs. As part of their analysis, Oulhote and Bouchard 

(2013) noted that their outcome assessment for behavioral problems may not have been as 

sensitive as Bouchard et al. (2010), which may in part account for the difference in the observed 

results from these studies. 

In addition, the three US cohorts and the CHARGE study have reported suggestive or positive 

associations between OP exposure and autism spectrum disorders (Rauh et al., 2006; Shelton et 

al., 2014; Eskenazi et al., 2007; Furlong et al., 2014). Specifically, Furlong et al. (2014) 

documented suggestive evidence of an association between total DEAP exposure and reciprocal 

social responsiveness among blacks and boys. Eskenazi et al. (2007) reported a statistically 

significant association between pervasive developmental disorder (PDD) and total DAP 

exposure, whereas Eskenazi et al. (2010) reported non-significant, but suggestive, increased odds 

of PDD of 2.0 (0.8 to 5.1; p=0.14). Rauh et al. (2006) documented a significant association 

between PDD and specifically chlorpyrifos exposure. Both PDD and reciprocal social 

responsiveness are related to the autism spectrum disorder. Using a different exposure 

assessment method (geospatial analysis and residential proximity to total OP exposure), Shelton 

et al. (2014) also showed statistically significant associations between total OP exposure and 

ASD. While these studies vary in the magnitude of the overall strength of association, they have 

consistently observed a positive association between OP exposure and ASD. Finally, CCCEH, 

Mt. Sinai, CHAMACOS have reported an inverse relation between the respective prenatal 

measures of chlorpyrifos and intelligence measures at age 7 years (Rauh et al. ,2011; Engel et al., 

2011; Bouchard et al., 2011). 

Across the epidemiology database of studies, the maternal urine, cord blood, and other 

(meconium) measures provide evidence that exposure did occur to the fetus during gestation but 

the actual level of such exposure during the critical window(s) of susceptibility is not known. 

While significant uncertainties remain about the actual exposure levels experienced by mothers 

and infant participants in the children’s health cohorts, it is unlikely that these exposures resulted 

in AChE inhibition. As part of the CHAMACOS study, Eskenazi et al. (2004) measured AChE 

activity and showed that no differences in AChE activity were observed. The biomarker data 

(chlorpyrifos) from the Columbia University studies are supported by the agency’s dose 

reconstruction analysis using the PBPK-PD model (D424485, D. Drew et al., 12/29/2014). 

Following the recommendation of the FIFRA SAP (2012), the agency conducted a dose 

reconstruction analysis of residential uses available prior to 2000 for pregnant women and young 

children inside the home. The PBPK-PD model results indicate for the highest exposure 
Page 26 of 152

considered (i.e., indoor broadcast use of a 1% chlorpyrifos formulation) <1% RBC AChE 

inhibition was produced in pregnant women. While uncertainty exists as to actual OP exposure 

at (unknown) critical windows of exposure, EPA believes it is unlikely individuals in the 

epidemiology studies experienced RBC AChE inhibition.

A review of the scientific literature on potential modes of action/adverse outcome pathways 

(MOA/AOP)8leading to effects on the developing brain was conducted for the 2012 FIFRA SAP 

meeting (USEPA, 2012) and updated for the December 2014 chlorpyrifos revised risk 

assessment (D424485, D. Drew et al., 12/29/2014). In short, multiple biologically plausible 

hypotheses and pathways are being pursued by researchers that include targets other than AChE 

inhibition, including cholinergic and non-cholinergic systems, signaling pathways, proteins, and 

others. However, no one pathway has sufficient data to be considered more credible than the 

others. The fact that there are, however, sparse AOP data to support the in vitro to in vivo

extrapolation, or the extrapolation from biological perturbation to adverse consequence 

significantly limits their quantitative use in risk assessment. The SAP concurred with the agency 

in 2008 and 2012 about the lack of definable key events in a MOA/AOP leading to 

developmental neurobehavioral effects. However, since the 2014 literature review, there are no 

substantive changes in the ability to define and quantitate steps in an MOA/AOP leading from 

exposure to effects on the developing brain. Published and submitted guideline DNT laboratory 

animal studies have been reviewed for OPs as part of the 2012/2014 review (D424485, D. Drew 

et al., 12/29/2014) and the updated 2015 review (OPP/USEPA; D331251; 

9/15/15). Neurobehavioral alterations in laboratory animals were often reported, albeit at AChE 

inhibiting doses, but there was generally a lack of consistency in terms of pattern, timing, or 

dose-response for these effects, and a number of studies were of lower quality. However, this 

information does provide evidence of long-lasting neurodevelopmental disorders in rats and mice 

following gestational exposure.

At this time, a MOA(s)/AOP(s) has/have not been established for neurodevelopmental outcomes. 

This growing body of literature does demonstrate, however, that OPs are biologically active on a 

number of processes that affect the developing brain. Moreover, there is a large body of in vivo

laboratory studies which show long-term behavioral effects from early life exposure, albeit at 

doses which cause AChE inhibition. EPA considers the results of the toxicological studies 

relevant to the human population, as qualitatively supported by the results of epidemiology 

studies. The agency acknowledges the lack of established MOA/AOP pathway and uncertainties 

associated with the lack of ability to make strong causal linkages and unknown window(s) of 

susceptibility. These uncertainties do not undermine or reduce the confidence in the findings of 

the epidemiology studies. The epidemiology studies reviewed in the 2012/2014 and 2015 

literature reviews represent different investigators, locations, points in time, exposure assessment 

procedures, and outcome measurements. Despite all these differences in study design, with the 

exception of two negative studies in the 2015 literature review (Guodong et al., 2012; Oulhote 

and Bouchard, 2013), authors have identified associations with neurodevelopmental outcomes 

associated with OP exposure across four cohorts and twelve study citations. Specifically, there is 

evidence of delays in mental development in infants (24-36 months), attention problems and 

autism spectrum disorder in early childhood, and intelligence decrements in school age children 

 

8 Mode of action (MOA) and adverse outcome pathways (AOPs) describe a set of measureable key events that make 

up the biological processes leading to an adverse outcome and the causal linkages between such events. 
Page 27 of 152

who were exposed to OPs during gestation. Investigators reported strong measures of statistical 

association across several of these evaluations (odds ratios 2-4 fold increased in some instances), 

and observed evidence of exposures-response trends in some instances, e.g., intelligence 

measures.

As section 408(b)(2)(C) of the FFDCA instructs EPA, in making its “reasonable certainty of no 

harm” finding, that in “the case of threshold effects, an additional tenfold margin of safety for the 

pesticide chemical residue and other sources of exposure shall be applied for infants and children 

to take into account potential pre- and postnatal toxicity and completeness of data with respect to 

exposure and toxicity to infants and children.” Section 408 (b)(2)(C) further states that “the 

Administrator may use a different margin of safety for the pesticide chemical residue only if, on 

the basis of reliable data, such margin will be safe for infants and children.” Given the totality of 

the evidence, there is sufficient uncertainty in the human dose-response relationship for 

neurodevelopmental effects which prevents the agency from reducing or removing the statutory 

10X FQPA Safety Factor. For the TCVP DRA, a value of 10X has been applied. Similarly, a 

database uncertainty factor of 10X will be retained for occupational risk assessments. The 

agency will continue to evaluate the epidemiology studies and pursue approaches for quantitative 

or semi-quantitative comparisons between doses which elicit AChE inhibition and those which 

are associated with neurodevelopmental outcomes prior to a revised human health risk 

assessment. 

4.5 Safety Factor for Infants and Children (FQPA Safety Factor)

No increased susceptibility was observed in the developmental and reproductive toxicity studies, 

and there was no evidence that the young animal is more sensitive to cholinesterase inhibition than 

the adult animal in the comparative cholinesterase assays (CCA). The quantitative susceptibility 

observed in pups at the high dose of 200 mg/kg/day in the DNT occurred at a dose 10-fold higher 

than doses reflecting 10% inhibition in juvenile pups in the CCA study and 25-fold higher than the 

point of departure. Therefore, quantitative sensitivity occurring at doses relevant for risk 

assessment was not observed in the TCVP database.

As noted above, the lack of an established MOA/AOP makes quantitative use of the 

epidemiology studies in risk assessment challenging, particularly with respect to determining 

dose-response, critical duration of exposure, and window(s) of susceptibility. However, 

exposure levels in the range measured in the epidemiology studies are likely low enough that 

they are unlikely to result in AChE inhibition. Epidemiology studies consistently identified 

associations with neurodevelopmental outcomes associated with OP exposure such as delays in 

mental development in infants (24-36 months), attention problems and autism spectrum disorder 

in early childhood, and intelligence decrements in school age children. Therefore, there is a need 

to protect children from exposures that may cause these effects; this need prevents the agency 

from reducing or removing the statutory FQPA Safety Factor. Thus, the FQPA 10X Safety 

Factor will be retained for TCVP for the population subgroups that include infants, 

children, youths, and women of childbearing age for all exposure scenarios. 
Page 28 of 152

4.5.1 Completeness of the Toxicology Database

The database of toxicology studies for TCVP is complete and includes developmental toxicity 

studies in the rat and rabbit, a reproductive toxicity study in the rat, acute and subchronic 

neurotoxicity studies in the rat, a developmental neurotoxicity study in the rat, a comparative 

cholinesterase study in the rat with three components (acute, repeat, and gestational exposure).

As discussed in Section 4.4, there is uncertainty in the human dose-response relationship for 

neurodevelopmental effects and this warrants retention of the FQPA Safety Factor for the 

population subgroups that include infants, children, youths, and women of childbearing age for 

all exposure scenarios.

4.5.2 Evidence of Neurotoxicity

TCVP is an organophosphate insecticide with an established neurotoxic AOP; neurotoxicity is 

the most sensitive effect in all species, routes, and lifestages and is being used to derive points of 

departure (PODs).

4.5.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

The concern for susceptibility is low based on the lack of susceptibility following in utero

exposure to TCVP in either the rat or rabbit developmental toxicity study or following in utero

and/or pre-/post-natal exposure to TCVP in the 2-generation reproduction rat study. The 

quantitative susceptibility observed in pups at the high dose of 200 mg/kg/day in the DNT 

occurred at a dose 10-fold higher than doses reflecting 10% inhibition in juvenile pups in the 

CCA study and 25-fold higher than the point of departure. Additionally, the maternal animal in 

the DNT was likely experiencing significant AChE inhibition at the dose level where 

developmental toxicity was observed. In the comparative cholinesterase studies following both 

acute and repeat exposure, as well as gestational exposure, there was no evidence that the young 

animal is more sensitive to cholinesterase inhibition than the adult animal. 

As discussed in Section 4.4, there is uncertainty in the human dose-response relationship for 

neurodevelopmental effects and this warrants retention of the FQPA Safety Factor for the 

population subgroups that include infants, children, youths, and women of childbearing age for 

all exposure scenarios.

4.5.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The mostly refined dietary risk 

assessment uses food residues levels from monitoring data and from empirical studies, percent 

livestock treated data and model-estimated drinking water concentrations from maximum 

application rates. Residential exposure assessments use data from surrogate and chemicalspecific sources. The exposure assumptions will not underestimate risks.
Page 29 of 152

4.6 Toxicology Endpoint and Point of Departure Selections

4.6.1 Dose-Response Assessment

Table 4.6.4.1 summarizes the TCVP toxicity endpoints and points of departure (PODs) selected 

from an evaluation of the database. This endpoint selection was based on a weight of the evidence 

evaluation using the following considerations:

 Relative sensitivity of the brain and RBC compartments: For TCVP, the brain and RBC 

compartments were generally similarly inhibited, as discussed in the toxicological effects 

section. AChE data were evaluated across several durations and studies (Table A.3.1 in 

Appendix A). However, based upon the robustness of the AChE data and dose-response 

across the dose selection in the 90-day toxicity rat study, the RBC AChE data from female 

rats were selected as the endpoint for deriving the acute and steady state POD for risk 

assessment. In this study the female RBC data were more robust than in males.

 Potentially susceptible populations (fetuses, juveniles, pregnant dams): The available 

AChE data across multiple lifestages (adults, pregnant females, fetuses, juveniles) from the 

acute and repeat CCA studies demonstrate no lifestage sensitivity for either RBC or brain 

AChE. The lowest dose in the acute CCA study was 75 mg/kg. Similar RBC AChE 

inhibition (20-40%) was observed at this dose in PND11 and PND21 juvenile pups as well 

as in the young adult. The gestational CCA component also demonstrate the lack of 

sensitivity of the fetus with derived a LOAEL of 75 mg/kg. A NOAEL from the CCA study 

was not identified and, hypothetically, a LOAEL to NOAEL factor would result in a 7.5 

mg/kg derived NOAEL, similar to the BMDL10 of 8 mg/kg/day. Therefore, reliance of 

adult female AChE data for risk assessment is protective of all lifestages. 

 Route of exposure: It is preferred to match, to the degree possible, the route of exposure 

in the toxicity study with the exposure scenario(s) of interest. In the case of TCVP, there 

are oral, dermal, and inhalation studies that contain measurements of AChE inhibition. 

 Duration of exposure: It is preferred to match, to the degree possible, the duration of 

toxicity study with the exposure duration of interest. In the case of TCVP, there are single 

day and steady state/repeat exposure oral studies and steady state dermal and inhalation 

studies. The oral AChE data, as discussed in section 4.3.2, show the magnitude of AChE 

inhibition does not significantly increase with dose such that AChE inhibition from a single 

oral dose was comparable to inhibition after repeated oral exposure. For example, the 

single dose study in adult rats demonstrates a NOAEL of 8 mg/kg for both brain and RBC 

AChE, and the RBC BMDL10 from the 90-day subchronic toxicity rat study is 8 mg/kg/day. 

As such, the same POD is being used for oral exposure across all durations.

 Consistency across studies: In cases where multiple datasets are available for a single 

duration, it is important to evaluate the extent to which data are consistent (or not) across 

studies. As discussed, the database shows a consistent shallow dose response across studies 

and durations demonstrating that TCVP is less potent than many organophosphates. 

However, the POD relied upon by the agency is conservative and health protective. 
Page 30 of 152

Descriptions of the primary toxicity studies used for selecting toxicity endpoints and points of 

departure for various exposure scenarios are presented in Appendix A of this document. Summary 

tables of BMD analyses can be found in Appendix B and the technical details of the analysis can 

be found in the BMD memo (J. Bever; TXR No. 0056970; D420286). 

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

benchmark response (BMR) level of 10% and has thus calculated BMD10s and BMDL10s. The 

BMD10 is the estimated dose where AChE is inhibited by 10% compared to background AChE 

activity. The BMDL10 is the lower confidence bound on the BMD10 value. As a matter of science 

policy, the agency uses the BMDL, not the BMD, for use as the PoD (USEPA, 2012). All 

BMD/BMDL modeling was completed using USEPA BMD Software, version 2.4; an exponential 

model was used to fit the data. 

Acute Dietary 

As presented earlier in Section 4.3.2 of the hazard assessment, the AChE data suggest lack of 

toxicity or greater inhibition with repeated exposure. Several lines of evidence suggest a NOAEL

of 8 mg/kg/day is protective for both acute and steady state assessments. The single dose study 

in adults demonstrates a NOAEL of 8 mg/kg for both brain and RBC AChE. The acute CCA 

study (juveniles, gestation, and young adult) provides a LOAEL of 75 mg/kg (lowest dose tested) 

and hypothetically the use of a 10x LOAEL to NOAEL UF would result in a 7.5 mg/kg POD. 

Likewise, the RBC BMDL10 from the 90-day subchronic toxicity rat study is 8 mg/kg/day. 

Therefore, a POD for the acute dietary (all populations) exposure scenario was derived based on 

the RBC AChE inhibition from the oral 90-day subchronic toxicity rat study (MRID 43371201). 

This 90-day rat study was selected since it provided the most robust dose-response RBC AChE 

data from doses relevant to risk assessment. The female BMDL10 of 8.0 mg/kg/day associated 

with RBC ChE inhibition in both sexes in the subchronic oral study was selected as the most 

protective and suitable POD for the acute dietary (all populations) exposure scenario. The 

corresponding BMD10 was 10.5 mg/kg/day. 

The FQPA SF (10X) will be retained for infants, children, youths, and women of childbearing 

age due to uncertainty in the human dose-response relationship for neurodevelopmental effects 

(see Section 4.4). The acute population adjusted dose (aPAD) for these lifestages is 0.008 

mg/kg/day (includes a total uncertainty factor of 1000X: 10X to account for interspecies 

extrapolation and 10X for intraspecies variation and the 10X FQPA SF). The only population 

subgroup for dietary exposure scenarios that the FQPA SF is not retained for is adults 50-99 

years of age; therefore, the aPAD for this population subgroup is 0.08 mg/kg/day.

Steady-State Dietary 

The steady state dietary endpoint was selected from an oral subchronic toxicity rat study 

conducted in which RBC AChE inhibition was observed. The duration of this study is considered 

appropriate for this exposure scenario since AChE data across the database demonstrate that 

there is no progression of AChE inhibition over duration with TCVP and that steady state 

inhibition occurs essentially after a single dose and within 21 days for other OPs, and a longerterm exposure would not be expected to result in a lower POD. The female BMDL10 of 8.0 
Page 31 of 152

mg/kg/day associated with RBC AChE inhibition in both sexes was selected as a suitable POD 

for the steady state dietary (all populations) exposure scenario. The steady state point of 

departure is protective of any exposure duration longer than 21-days, including chronic exposure, 

since cholinesterase inhibition does not increase after reaching maximum inhibition or steady 

state.

The FQPA SF (10X) will be retained for infants, children, youths, and women of childbearing 

age due to uncertainty in the human dose-response relationship for neurodevelopmental effects 

(see Section 4.4). The steady state population adjusted dose (ssPAD) for these lifestages is 0.008 

mg/kg/day (includes a total uncertainty factor of 1000X: 10X to account for interspecies 

extrapolation and 10X for intraspecies variation and the 10X FQPA SF). The only population 

subgroup for dietary exposure scenarios that the FQPA SF is not retained for is adults 50-99 

years of age; therefore, the ssPAD for this population subgroup is 0.08 mg/kg/day.

Incidental Oral, Steady State

For the purpose of assessing potential risk associated with incidental oral exposure from steady 

state durations, OPP selected the POD and endpoint from an oral subchronic toxicity study 

conducted in adult rats in which RBC cholinesterase inhibition was observed. This study is 

appropriate for a childrens assessment since the acute and repeat CCA studies did not demonstrate 

sensitivity of juvenile pups compared to adults. Therefore, quantitation of incidental oral risks 

was performed using the female BMDL10 value of 8.0 mg/kg/day, based on RBC AChE inhibition 

and the BMD10 of 10.5 mg/kg. The selected study is protective of all populations since there is no 

concern for increased quantitative susceptibility in acute and repeated dosing CCA studies. 

A total uncertainty factor of 1000X is appropriate for incidental oral exposures (10X for 

interspecies extrapolation, 10X for intraspecies variation, and a 10X FQPA SF due to uncertainty 

in the human dose-response relationship for neurodevelopmental effects (see Section 4.4)). 

Dermal, Steady State

No quantification of dermal non-cancer risk is required for TCVP. There were (1) no treatment 

related effects (no clinical signs) at doses up to and including the limit dose in the dermal toxicity 

study; (2) both RBC and brain cholinesterase activity were assessed in the dermal study and neither 

compartment was affected at the limit dose; (3) there is no concern for quantitative susceptibility 

for juvenile or gestational lifestages based on results of the developmental, reproductive, or CCA 

toxicity studies; and (4) the effects observed in pups from the DNT were 10-fold above the 10% 

inhibition level with a dermal equivalent dose necessary to produce an effect well above the limit 

dose. 

Inhalation, Steady State

The steady state inhalation POD was selected from a 4-week inhalation toxicity study (MRID 

48803501) in rats, based on an increase in RBC cholinesterase inhibition in both sexes. Females 

had slightly lower modeled values (BMDL10 of 0.022 mg/L/day: BMD10 of 0.12 mg/L/day). The 

duration of this study is considered appropriate for the steady state exposure scenario since steady 

state occurs within 21 days, as demonstrated for other OPs, and a longer-term exposure would not 

be expected to result in a lower POD. The methods and dosimetry equations described in the 

agency’s reference concentration (RfC) guidance are suited for calculating human equivalent 
Page 32 of 152

concentrations (HECs) based on the inhalation toxicity POD obtained in rats exposed for 6 hr/day 

for an average of 5.5 days/week. The regional deposited dose ratio (RDDR), which accounts for 

the particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard 

deviation [GSD] of aerosols) can be used to estimate the different dose fractions deposited along 

the respiratory tract surface areas. Thus, the RDDR can be used to adjust an observed inhalation 

particulate exposure of an animal to the predicted inhalation exposure for a human. For the 

subchronic inhalation toxicity study with TCVP, a RDDR of 2.525 was estimated based on 

extrarespiratory effects (RBC AChE inhibition) in Sprague Dawley rats (bodyweight = 267g). The 

MMAD and GSD of 2.57 and 3.785 μm, respectively, at 0.05 mg/L were used to derive the RDDR. 

The HECs are summarized in Table 4.6.1.1, as well as human equivalent doses (HEDs) 

calculated for residential and occupational handler scenarios. For residential handler scenarios, a 

HED was calculated using a breathing rate of 16.7 L/min. For occupational handler scenarios, 

HEDs were calculated for breathing rates of 8.3, 16.7, and 29 L/min to account for different 

occupational activities. The standard interspecies extrapolation uncertainty factor can be reduced 

from 10X to 3X due to the HEC calculation accounting for pharmacokinetic (not 

pharmacodynamic) interspecies differences. The intraspecies uncertainty factor remains at 10X. 

Table 4.6.1.1 Estimated Human Equivalent Concentration (HEC)/Human Equivalent Dose (HED)

Population HEC (mg/L) HED (mg/kg/day)

Residential Handler 0.05555 1.590

Residential Bystander 0.00992 -

Occupational

-8.3 L/min breathing rate

-16.7 L/min breathing rate

-29 L/min breathing rats

0.04166

2.371

4.771

8.285

RDDR = 2.525 (extrarespiratory) based on MMAD±GSD of 2.57±3.785 observed at 0.05 mg/L in SpragueDawley rats using 267g default bodyweight (MRID 48803501).

A total uncertainty factor of 300X is appropriate for inhalation exposures (3X for interspecies 

extrapolation, 10X for intraspecies variation, and a 10X FQPA SF for residential assessments or a 

10X database uncertainty factor in occupational assessments due to uncertainty in the human doseresponse relationship for neurodevelopmental effects (see Section 4.4)).

4.6.2 Recommendations for Combining Routes of Exposure for Risk Assessment

PODs for the oral, dermal, and inhalation routes are all derived from RBC cholinesterase 

inhibition. The data do not support any differences in response across different lifestages or sexes. 

Thus, all routes can be combined.

4.6.3 Cancer Classification and Risk Assessment Recommendation

TCVP is classified as a Group C, possible human carcinogen, based on statistically significant 

increases in combined hepatocellular adenoma/carcinoma (primarily carcinomas) in the female 

B6C3F1 mouse, suggestive evidence of thyroid c-cell adenomas, and adrenal pheochromocytomas 

in the rat, as well as mutagenicity concerns. A cancer potency factor (Q1 *) of 1.83 x 10-3 

(mg/kg/day)-1was estimated using the Weibull 83 time-to-tumor model. A 3/4 body weight scaling 

factor was used to convert from mouse to human equivalents.
Page 33 of 152

4.6.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

See Table 4.6.4.1 below.
Page 34 of 152

Table 4.6.4.1. Summary of Toxicological Doses and Endpoints for TCVP for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors*

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(all 

populations, 

except adults 

50-99)

BMDL10 = 8.0 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

10x

Acute RfD = 

0.08 mg/kg/day

aPAD = 0.008 

mg/kg/day

Subchronic Oral Toxicity Study (MRID 

43371201) – Rat

BMD10 = 10.49 mg/kg/day, based on 

female RBC AChE inhibition

Acute Dietary 

(Adults 50-

99)

BMDL10 = 8.0 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

1x 

Acute RfD = 0.08 

mg/kg/day

aPAD = 0.08 

mg/kg/day

Subchronic Oral Toxicity Study (MRID 

43371201) - Rat

BMD10 = 10.49 mg/kg/day, based on 

female RBC AChE inhibition

Steady State 

Dietary (all 

populations,

except adults 

50-99)

BMDL10 = 8.0 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

10x

Steady State RfD 

= 0.08 mg/kg/day

ssPAD = 0.008 

mg/kg/day

Subchronic Oral Toxicity Study (MRID 

43371201) – Rat

BMD10 = 10.49 mg/kg/day, based on 

female RBC AChE inhibition

Steady State 

Dietary 

(Adults 50-

99)

BMDL10 = 8.0 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

1x

Steady State RfD 

= 0.08 mg/kg/day

ssPAD = 0.08 

mg/kg/day 

Subchronic Oral Toxicity Study (MRID 

43371201) – Rat

BMD10 = 10.49 mg/kg/day, based on 

female RBC AChE inhibition

Incidental 

Oral

(steady state) BMDL10 = 8.0 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF = 

10x

Residential LOC 

for MOE = 1000

Subchronic Oral Toxicity Study (MRID 

43371201) – Rat

BMD10 = 10.49 mg/kg/day, based on 

female RBC AChE inhibition

Dermal 

(steady state)

No potential hazard via the dermal route, based on the lack of treatment-related effects, including 

the lack of RBC and brain cholinesterase inhibition following repeat dermal exposure of rats at 

dose levels up to 1000 mg/kg/day and no concern for quantitative susceptibility. 

Inhalation 

(steady state)

BMDL10=0.022 

mg/L/day 

(males)

UFA= 3x

UFH=10x

FQPA SF = 

10X

Residential LOC 

for MOE = 300

Subchronic Inhalation Toxicity Study 

(MRID 48803501) – Rat

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

AChE 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
Page 35 of 152

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 

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. RBC = red blood cell. 

BMDL10= benchmark dose lower limit for 10% response. PAD = population adjusted dose. (a = acute. ss = steady state or 

maximal AChE inhibition which occurs around 2-3 weeks for OPs and is a specific exposure assessment conducted for OPs 

instead of the traditional short, intermediate, or chronic assessments. The SS assessment is protective of longer durations 

including chronic).

*The 10X FQPA SF is retained for infants, children, youths, and women of childbearing age for all exposure scenarios due to 

uncertainty in the human dose-response relationship for neurodevelopmental effects (see Section 4.4). This includes all exposure 

scenarios, except the dietary exposure scenarios for the population subgroup adults 50-99 for which the FQPA SF has been 

reduced to 1X.

Table 4.6.4.2 Summary of Toxicological Doses and Endpoints for TCVP for Use in Occupational Human 

Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

(steady state) No potential hazard via the dermal route, based on the lack of treatment-related effects, including 

the lack of RBC and brain cholinesterase inhibition following repeat dermal exposure of rats at 

dose levels up to 1000 mg/kg/day and no concern for quantitative susceptibility. 

Inhalation 

(steady state) BMDL10=0.022 

mg/L/day (males)

UFA= 3x

UFH=10x

UFDB= 10x*

Occupational 

LOC for MOE 

= 300

Subchronic Inhalation Toxicity Study

(MRID 48803501) - Rat

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

AChE 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 

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); UFDB = database uncertainty factor; MOE = margin of exposure. LOC = level 

of concern. RBC = red blood cell. BMDL10= benchmark dose lower limit for 10% response. SS = steady state or maximal AChE 

inhibition which occurs around 2-3 weeks for OPs and is a specific exposure assessment conducted for OPs instead of the 

traditional short, intermediate, or chronic assessments. The SS assessment is protective of longer durations including chronic.

*The 10X database uncertainty factor applies to occupational worker assessment to account for potentially pregnant workers due 

to uncertainty in the human dose-response relationship for neurodevelopmental effects (see Section 4.4). 
Page 36 of 152

4.7 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,

reproductive, and general or systemic toxicity. These studies include endpoints which may be

susceptible to endocrine influence, including effects on endocrine target organ histopathology,

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and

chronic studies that assess growth, developmental and reproductive effects in different

taxonomic groups. As part of its reregistration decision for TCVP, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), TCVP is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems. Chemicals that go through Tier 1 screening and are found to have the potential to

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2

testing is designed to identify any adverse endocrine-related effects caused by the substance, and

establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20139and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. TCVP is on List 1 for 

which EPA has received all the required Tier 1 assay data. The agency has reviewed all of the 

assay data received for the appropriate List 1 chemicals and the conclusions of those reviews are 

available in the chemical-specific public dockets 

(http://www2.epa.gov/sites/production/files/2015-06/documents/tetrachlorvinphos083701_2015-06-29_txr0057147.pdf). For further information on the status of the EDSP, the 

policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website10.

 

9

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

10 http://www.epa.gov/endo/
Page 37 of 152

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

Residue Chemistry Memo: DP# 243528, 3/11/98, D. Miller

Residue Chemistry Memo: DP# 206721, 9/21/94, D. Miller (Addendum to RED)

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94, F. Suhre)

Residue Chemistry Memo: J. Abbotts, No DP#, 4/93, Results of Metabolism Committee Meeting

There are no registrations or tolerances for plant commodities, so plant metabolism studies are 

not required for TCVP. The qualitative nature of the residue in ruminants following oral or 

dermal dosing, and in poultry following dermal application, is adequately understood based on 

previously submitted studies. The HED Metabolism Committee (9/8/93 Meeting) has 

determined that the residues of concern for tolerance enforcement and for risk assessment for 

carcinogenicity are the parent compound and four metabolites: tetrachlorvinphos, des-O-methyl 

tetrachlorvinphos, 1-(2,4,5-trichlorophenyl)ethanol (free and conjugated forms), 2,4,5-

trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)ethanediol. For the non-cancer risk 

assessment for cholinesterase inhibition, tetrachlorvinphos is the only residue of concern.

5.1.2 Summary of Environmental Degradation

Drinking Water Assessment Memo (EFED): DP# 419448, 11/6/14, C. Peck

TCVP is moderately mobile in soil and not stable in terrestrial or aquatic environments. The TCVP 

degradates appear to be as mobile, and in most cases more mobile, than the parent. TCVP is soluble 

in water at up to 11.6 mg/L, and is not expected to volatilize significantly due to a low vapor 

pressure of 2.6 x 10-7torr (25°C). The compound is hydrophobic (Log Kow of 3.53). TCVP 

hydrolyzes in water at a pH-dependent rate. Hydrolysis is relatively rapid in alkaline water (halflife of 10.3 days at pH 9). In neutral to acidic water (pH 5 to 7), TCVP hydrolyzes with slower 

half-lives of 30 to 57 days. A major degradate of hydrolysis found in the aqueous solution at pH 

9 was des-O-methyl tetrachlorvinphos (28% at Day 21). Hydrolysis rates for the TCVP TRC could 

not be calculated, as not all degradates in the study extracts were identified; therefore, TCVP TRC 

was considered stable to hydrolysis. Photolysis studies of TCVP have not been submitted (not 

required for residential outdoor use).

TCVP isomer mixture (50:50, Z:E) readily biodegraded in aerobic soils, with a half-life of 

approximately 9 days. However, the rate of biodegradation for the mixed isomer of the parent 

TCVP was slightly reduced as concentrations decreased, which may indicate that one isomer 

degrades more rapidly than the other. Major soil degradates include TCPEol, TCCEol, TCPEone 

and TCBA. The TCVP TRC that were identified in the aerobic soils biodegraded with half-lives 

of from 53 to 200 days. 

5.1.3 Comparison of Metabolic Pathways

Metabolism in ruminants (dermal and oral administration; tissue), poultry (oral; tissue) and rats 

(oral; excreta) is similar, generally resulting in parent TCVP and the four metabolites of concern

(TCVPdeme, TCPEdiol, TCPEone and TCPEol). However, the metabolite TCPEone was not 
Page 38 of 152

found in detectable levels in the rat metabolism study and the metabolite TCPEdiol was not 

detected in the goat studies. Unchanged parent TCVP was found in the goat dermal study, but 

was not detected in the goat oral study.

5.1.4 Residues of Concern Summary and Rationale

The HED Metabolism Committee (9/8/93 Meeting) has determined that the total residues of 

concern (TRC) for carcinogenicity are the parent compound tetrachlorvinphos and metabolites 

which, like tetrachlorvinphos, contain the 2,4,5 trichlorobenzene ring. For livestock 

commodities, the total residues of concern for carcinogenicity are tetrachlorvinphos [TCVP] plus 

the following four metabolites: des-O-methyl tetrachlorvinphos [TCVPdeme]; 1-(2,4,5-

trichlorophenyl)ethanol (free and conjugated forms) [TCPEol]; 2,4,5-trichloroacetophenone 

[TCPEone]; and 1-(2,4,5-trichlorophenyl)ethanediol [TCPEdiol]. For drinking water 

carcinogenicity assessment, the total residues of concern include the four aforementioned 

metabolites for livestock plus 2 additional degradates: l-(2,4,5-trichlorophenyl)-2-chloroethanol 

[TCCEol], and 2,4,5-trichlorobenzoic acid [TCBA].

For the non-cancer risk assessment for cholinesterase inhibition, TCVP is the only residue of 

concern. For tolerance enforcement the residues of concern include TCVP plus, TCVPdeme, 

TCPEdiol, TCPEone and TCPEol.

See Appendix D for a table of parent and metabolite structures and chemical properties.

Table 5.1.4 Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix

Residues included in 

Risk Assessment 

(Cholinesterase 

Inhibition)

Residues included in 

Risk Assessment 

(Carcinogenicity)

Residues included in 

Tolerance Expression

Plants

Primary Crop NA NA NA

Rotational 

Crop NA NA NA

Livestock

Ruminant TCVP

TCVP, TCVPdeme, 

TCPEdiol, TCPEone and 

TCPEol

TCVP, TCVPdeme, 

TCPEdiol, TCPEone and 

TCPEol

Poultry TCVP

TCVP, TCVPdeme, 

TCPEdiol, TCPEone and 

TCPEol

TCVP, TCVPdeme, 

TCPEdiol, TCPEone and 

TCPEol

Drinking Water TCVP

TCVP, TCVPdeme, 

TCPEdiol, TCPEone and 

TCPEol, TCCEol, TCBA

NA

NA= not applicable

TCVP= tetrachlorvinphos

TCVPdeme,= des-O-methyl tetrachlorvinphos

TCPEol= 1-(2,4,5-trichlorophenyl)ethanol (free and conjugated forms)

TCPEone= 2,4,5-trichloroacetophenone

TCPEdiol= 1-(2,4,5-trichlorophenyl)ethanediol

TCCEol =l-(2,4,5-trichlorophenyl)-2-chloroethanol
Page 39 of 152

TCBA =2,4,5-Trichlorobenzoic acid

5.2 Residue Chemistry and Food Residue Profile

Residue Chemistry Memo: DP# 243528, 3/11/98, D. Miller

Dietary Assessment Memo: DP#426985, 10/29/15, D.Drew

Residue Chemistry

Tolerances are established for residues of TCVP in animal commodities since residues may 

occur in milk, eggs, meat, fat, or meat byproducts as a result of the registered uses on livestock 

(oral and dermal uses) and around livestock premises. There are no registered uses on plant 

(including feedstuffs) commodities. This section provides the background and current status of 

residue chemistry requirements for TCVP and includes residue data submitted and reviewed 

since the 1994 Residue Chemistry Chapter of the TCVP RED and the 2006 TCVP RED. 

The 1994 Residue Chemistry Chapter cited the need for the following magnitude of the residue 

studies: New magnitude of the residue studies reflecting oral and dermal exposure of beef cattle, 

dairy cattle, and hogs, and dermal exposure of poultry to tetrachlorvinphos are required. All 

residues of concern should be analyzed in cattle, hogs, and poultry using validated analytical 

methods.

Subsequent to the TCVP RED, in 2007, residue studies on cattle (dermal and oral treatments; 

MRID 47193001) and poultry (dermal treatment; MRID 47193001) were submitted, as was a 

companion storage stability study (MRID 47193001) and a residue analytical method (MRID 

47369201). Those studies were reviewed under DP #s D320848, D320858, D320859, and 

D381350 (C. Olinger, 10/7/10, Tetrachlorvinphos. Cattle Oral/Dermal and Poultry Dermal 

Studies. Summary of Residue Data Submitted in Support of Reregistration). The submitted 

magnitude of the residue studies on cattle and poultry were determined to be inadequate, but 

upgradeable pending submission of supporting storage stability data. The companion storage 

stability study was determined to be unacceptable because of study design. Additional 

information was also requested regarding the maximum storage duration of all samples collected 

from both the cattle and poultry studies. In 2011, additional information (MRIDs 486378101 and 

48319001) pertaining to the storage stability deficiencies was submitted and reviewed (C. 

Olinger, 3/25/11, D385359 and D386954, Tetrachlorvinphos. Response to Comment on Storage 

Stability Residue Data Deficiencies). The poultry and cattle residue data (860.1480) deficiencies 

are now fulfilled and no further data are being required.

In response to the data requirement for a residue study in hogs, a waiver request was submitted and 

granted in 2011 (C. Olinger, 4/25/11, D320857, Tetrachlorvinphos. Request for Waiver of a Swine 

Magnitude of Residue Study). It was determined that TCVP residues in swine tissues are not likely to be 

higher than the residues in ruminants and that ruminant data may be translated to swine. The conclusion 

was based on the poor oral and dermal absorption of TCVP in livestock and the fact that residence time in 

swine intestines is significantly shorter relative to that in a ruminant. No additional residue data 

(860.1480) on hogs are being required. 

In response to a TCVP Generic Data Call-In (GDCI) issued 12/29/09, data were submitted 

evaluating TCVP metabolites using the FDA Multiresidue Methods Test guidelines in Pesticide 

Analytical Manual (PAM) Vol. I (MRID 48655201) and were reviewed 7/5/12 (D. Drew, 
Page 40 of 152

D396833, Tetrachlorvinphos (TCVP). Multiresidue Methods (MRM) Study of the Metabolites 

of TCVP). The data requirement for MRM testing (860.1360) has been fulfilled. 

The registrant submitted a proposed method SCR/006 for tolerance enforcement of livestock 

commodities that includes detection of TCVP and the metabolites TCVPdeme, TCPEol, 

TCPEone and TCPEdiol (MRID 47369201, 2007). The HED review (D320848, D320858, 

D320859, and D381350) determined that the method was adequate, but that an independent 

laboratory validation (ILV) trial remained outstanding. A Generic Data Call-In (GDCI) for an 

ILV was originally issued December 29, 2009. A different proposed method (Method 

14020.6106) and an associated ILV study (Method 14020.6107) were subsequently submitted to 

the agency (MRID 49419301, 2015). Because the proposed Method 14020.6106 monitors only a 

single ion transition for each analyte, alternative confirmatory procedures are necessary; the 

previously submitted method SCR/006 (MRID 47369201) is considered acceptable as a 

confirmatory method. The analytical method test data for 14020.6106 are classified as 

scientifically acceptable for use as an analytical method for ruminant and poultry commodities.

Food Residue Profile

The available magnitude of the residue study for dairy cattle reflect a combination of two 

treatments: oral administration of tetrachlorvinphos for 29-31 days at actual rates of 1.512-1.555 

and 4.630 g ai/750 kg BW per day (6.3-6.5x and 19.3x, respectively, the maximum registered 

rate of 0.24 g ai/750 kg BW for feed-through treatment) and dermal spray treatments on three 

occasions, at ~14 day intervals, at actual rates of 10.111 and 19.166-19.493 g ai per animal per 

dose (~0.5 and 1.0x, respectively, the maximum registered rate of 18.9 g ai/animal for direct 

animal spray treatment). At the combined treatment regime (6.5x dermal spray plus 1x oral 

treatment), the maximum total residues of concern (with the maximum residues of the parent in 

parentheses) were: 0.072 (0.036) ppm for milk, 0.078 (<0.01) ppm for cream, 0.158 (<0.01) 

ppm for liver, 0.278 (0.015) ppm for kidney, 0.272 (0.212) ppm for muscle, 0.842 (0.558) ppm 

for subcutaneous fat, and 0.747 (0.340) ppm for peritoneal fat.

The available magnitude of the residue study for poultry reflects 6-7 dermal spray treatments of 

laying hens with an EC formulation, made at two-week retreatment intervals, at 0.0908, 0.1816, 

or 0.5448 g ai/hen/application. These application rates, respectively, correspond to ~0.5x, 1.0x, 

or 2.9x the maximum registered direct spray treatment rate of 0.19 g ai/bird daily. At ~1.0x, the 

maximum total residues of concern (with the maximum residues of the parent in parentheses) 

were: 0.288 (0.026) ppm for egg, 0.517 (0.016) ppm for liver, 0.583 (0.022) ppm for kidney, 

0.396 (0.082) ppm for muscle, 19.405 (6.030) ppm for skin with fat, and 1.298 (0.099) ppm for 

abdominal fat. 

There were no detectable residues of parent TCVP in the most recent USDA PDP monitoring 

data for beef meat, liver, or fat, or for milk and cream; nor were there detectable residues in pork 

fat. There were no detectable residues in chicken meat or liver. There was one detectable residue 

in egg just above the method limit of detection (LOD; 742 samples). PDP did not analyze 

chicken fat or skin for TCVP. The TCVP metabolites of concern for cancer assessment were not 

measured by PDP.

5.3 Water Residue Profile

Drinking Water Assessment Memo (EFED): DP# 419448, 11/6/14, C. Peck
Page 41 of 152

The Surface Water Concentration Calculator (SWCC) computer model was used to generate 

surface water Estimated Drinking Water Concentrations (EDWCs) for use in the human health 

dietary risk assessment, while the PRZM-GW and SCI-GROW models were used to generate 

groundwater EDWCs. The residues of concern for acute and steady state dietary exposure 

included cholinesterase-inhibiting compounds, which were determined to be TCVP parent only. 

For carcinogenicity, (total) residues of concern (TRC) included TCVP and the following 

metabolites which, like TCVP, contain the 2,4,5 trichlorobenzene ring: des-O-methyl 

tetrachlorvinphos,1-(2,4,5-trichlorophenyl)ethanediol, TCPEol (1-(2,4,5-

trichlorophenyl)ethanol), TCPEone (2,4,5-trichloroacetophenone), TCCEol (l-(2,4,5-

trichlorophenyl)-2-chloroethanol), and TCBA (2,4,5-trichlorobenzoic acid). 

Maximum EDWCs (based on maximum labeled usage for kennels, poultry droppings, garbage 

and manure piles, and corrals) for TCVP residues in surface water and groundwater for dietary 

assessment are presented in Table 5.3. Daily time series outputs for the thirty year simulation 

were also provided to HED for use in dietary exposure modeling.

This dietary assessment used the maximum total residues of concern (TRC) EDWC of 22.4 ug/L 

for the cancer analysis, input as a single point estimate. For the acute analysis, the conservative 

highest acute EDWC of 4.03 ug/L (TCVP only) was used as a single point estimate. For the 

steady state analysis, the entire distribution of 21-day averages from a thirty year simulation was 

used. 

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations 

for Tetrachlorvinphos

DRINKING WATER 

SOURCE (MODEL 

USED)

MAXIMUM ESTIMATED DRINKING WATER 

CONCENTRATION (EDWC)

Acute (μg/L)

(TCVP only)

Cancer (μg/L)

(TRC)

Surface water

(SWCC) 4.03 4.11

Groundwater (PRZMGW) 8.54x10-5 22.4

Groundwater 

(SCI-GROW) 5.61x10-3 7.36x10-2

* EDWCs based on maximum labeled usage for kennels, poultry droppings, garbage and manure piles, and corrals.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

HED has conducted acute, steady state, and cancer dietary (food and drinking water) exposure 

and risk assessments using DEEM version 3.16 for TCVP. OPs exhibit 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. OP AChE 

studies of 2-3 weeks generally show the same degree of inhibition as those of longer duration 

(i.e., up to 2 years of exposure). Therefore, a steady state assessment based on 21 days of 

exposure may be conducted in place of the traditional chronic assessment. 
Page 42 of 152

For steady state dietary assessments for OP pesticides, the DEEM acute module may be used to 

conduct two-day average assessments which uses two-day average food and water consumptions

along with the steady state POD. These two-day average assessments provide an estimate of 21-

day (steady state) average daily food and drinking water exposures. For the two-day average 

assessments, using a 21-day forward-rolling average water distribution file provides an accurate 

overall estimate of the 21-day (“steady-state”) average daily exposures at the per-capita 95th

percentile for drinking water, to the extent that predicted drinking water concentrations for any 

21-day duration is known for any given year. For food alone, the two-day average assessments 

reflect an average daily exposure for a two-day exposure duration rather than a 21-day exposure 

duration. Since the DEEM two-day average assessment does not capture day to day variation in 

food residues, it will generally result in higher food-only exposure estimates than a model that 

calculates 21-day rolling averages for food. Although the DEEM two-day average assessment for 

TCVP may result in higher exposure estimates for both water and food than would a 21-day 

average model, the assessment provides an acceptable estimate of steady state exposure for food 

and drinking water for use in risk assessment and will not underestimate the risk. 

TCVP dietary risk assessments were performed for the following population groups: the general 

U.S. population, all infants (<1 year old), children 1-2, children 3-5, children 6-12, youth 13-19, 

adults 20-49, females 13-49, and adults 50-99 years old. The lifestage relevant to TCVP cancer 

assessment is adults and the reported population for the cancer dietary assessment is the general 

U.S. population.

The dietary exposure analyses for TCVP are refined. The only food forms included in the 

analyses are based on animal commodities. The food residues were based upon U. S. Department 

of Agriculture’s Pesticide Data Program (USDA PDP) monitoring data except in a couple of 

instances where no appropriate PDP data were available (i.e., high-end residues from poultry 

dermal studies were used for poultry fat and poultry skin). The Biological and Economic 

Analysis Division (BEAD) of OPP provided percent livestock treated information. Modelderived estimated drinking water concentrations (EDWCs) were provided by the Environmental

Fate and Effect Division (EFED). EDWCs were based on spot applications to kennels, poultry 

droppings, garbage and manure piles, and corrals and were directly incorporated into the 

assessments as described in Section 5.3 above.

Since the PDP only analyzed for residues of TCVP (and not for TCVP metabolites) a factor was 

applied to the PDP residues in order to account for all the metabolites of concern for the cancer 

assessment. The factor was calculated by determining the ratio of parent TCVP to total residues 

of concern in the livestock residue studies (see Table 2, D426985).

5.4.2 Percent Crop Treated Used in Dietary Assessment

For the acute and steady state analyses, the maximum estimated percent livestock treated of 3% 

was used for cattle and swine and the estimated maximum of 11% was used for poultry.

For the cancer analysis, the following estimated average percent livestock treated was used: 1% 

for dairy cattle, 2% for beef cattle and swine, and 6% for poultry. 
Page 43 of 152

5.4.3 Acute Dietary Risk Assessment

The acute dietary risk estimates are below HED’s level of concern (<100 % of the acute 

population adjusted dose (aPAD)) for all population subgroups. Combined dietary exposure 

from food and drinking water at the 99.9th percentile of exposure is 73% of the aPAD for 

children (3-5 years old), the most highly exposed population subgroup (Table 5.4.3 below).

Acute exposures to TCVP from food consumption are higher than those from drinking water. 

Most of the exposure from food is due to the high-end residue on chicken skin from poultry 

dermal studies (residue on uncooked chicken skin from direct dermal spray applications at 

maximum labeled rates with a 0-day pre-slaughter interval).

Table 5.4.3. Results of Acute Dietary Exposure Analysis for TCVP Food only, Drinking Water only, and 

Food plus Drinking Water

Population 

Subgroup

aPAD

(mg/kg/day)1

Food only Drinking Water only Food plus Drinking 

Water 

99.9th Percentile 99.9th Percentile 99.9th Percentile

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% aPAD Exposure 

(mg/kg/day)

% 

aPAD

General U.S. 

Population 0.008 0.002873 36 0.000688 8.6 0.002954 37

All Infants (<1 

year old) 0.008 0.002749 34 0.001366 17 0.003017 38

Children 1-2 

years old 0.008 0.004902 61 0.001257 16 0.004896 61

Children 3-5 

years old 0.008 0.005585 70 0.000676 8.4 0.005841 73

Children 6-12 

years old 0.008 0.004134 52 0.000531 6.6 0.004260 53

Youth 13-19 

years old 0.008 0.003378 42 0.000455 5.7 0.003412 43

Adults 20-49 

years old 0.008 0.002657 33 0.000468 5.8 0.002777 35

Females 13-49 

years old 0.008 0.002348 29 0.000452 5.6 0.002416 30

Adults 50-99 

years old 0.08 0.001749 2.2 0.000460 <1 0.001826 2.3

*Population with the greatest exposure is in bold.

5.4.4 Steady State Dietary Risk Assessment

The steady state dietary exposure estimates are below HED’s level of concern (<100% of the 

steady state population adjusted dose (ssPAD)) for all population subgroups. Combined dietary 

exposure from food and drinking water at the 99.9th percentile of exposure is 43% of the ssPAD 

for children (3-5 years old), the most highly exposed population subgroup (Table 5.4.4 below).

Steady state exposures to TCVP from food consumption are higher than those from drinking 

water. Most of the exposure from food is due to the high-end residue on chicken skin from 

poultry dermal studies. 
Page 44 of 152

Table 5.4.4. Results of Steady State Dietary Exposure Analysis for TCVP Food only, Drinking Water only, 

and Food plus Drinking Water

Population 

Subgroup

ssPAD

(mg/kg/day)1

Food only Drinking Water only Food plus Drinking 

Water 

99.9th Percentile 99.9th Percentile 99.9th Percentile

Exposure 

(mg/kg/day)

% 

ssPAD

Exposure 

(mg/kg/day)

% 

ssPAD

Exposure 

(mg/kg/day)

% 

ssPAD

General U.S. 

Population 0.008 0.002041 26 0.000096 1.2 0.002046 26

All Infants (<1 

year old) 0.008 0.001850 23 0.000300 3.8 0.001875 23

Children 1-2 

years old 0.008 0.003242 40 0.000143 1.8 0.003274 41

Children 3-5 

years old 0.008 0.003468 43 0.000114 1.4 0.003459 43

Children 6-12 

years old 0.008 0.003020 38 0.000085 1.1 0.003005 38

Youth 13-19 

years old 0.008 0.002170 27 0.000075 1.0 0.002188 27

Adults 20-49 

years old 0.008 0.001983 25 0.000094 1.2 0.001989 25

Females 13-49 

years old 0.008 0.001571 20 0.000095 1.2 0.001557 19

Adults 50-99 

years old 0.08 0.001128 1.4 0.000087 <1 0.001132 1.4

*Population with the greatest exposure is in bold.

5.4.5 Cancer Dietary Risk Assessment

The estimated cancer dietary (food and drinking water) exposure of the general U.S. population 

to TCVP and its metabolites containing the 2,4,5 trichlorobenzene moiety is 0.000566 

mg/kg/day. Applying the Q1* of 0.00183 (mg/kg/day)-1to the exposure value results in a cancer 

risk estimate of 1 x 10-6(Table 5.4.5 below). Drinking water is the major contributor to the 

cancer dietary exposure.

Table 5.4.5. Results of Cancer Dietary Exposure Analysis for TCVP and Metabolites for Food only,

Drinking Water only, and Food plus Drinking Water

Population 

Subgroup

Q*

(mg/kg/day)-1

Food only Drinking Water only Food plus Drinking 

Water 

Exposure 

(mg/kg/day) Risk Exposure (mg/kg/day) Risk Exposure (mg/kg/day)

Risk

General U.S. 

Population

(Adults)

0.00183 0.000097 2 x 10-7 0.000469 9 x 10-7 0.000566 1 x 10-6
Page 45 of 152

5.4.6 Summary of Dietary (Food and Drinking water) Exposure and Risk Assessment

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Tetrachlorvinphos

Population Subgroup1

Acute Dietary

(99.9th Percentile)

Steady State

(99.9th Percentile) Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% ssPAD

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.002954 37 0.002046 26 0.000566 1 x 10-6

All Infants (<1 year old) 0.003017 38 0.001875 23

NA

Children 1-2 years old 0.004896 61 0.003274 41

Children 3-5 years old 0.005841 73 0.003459 43

Children 6-12 years old 0.004260 53 0.003005 38

Youth 13-19 years old 0.003412 43 0.002188 27

Adults 20-49 years old 0.002777 35 0.001989 25

Females 13-49 years old 0.002416 30 0.001557 19

Adults 50-99 years old 0.001826 2.3 0.001132 1.4

*Population with the greatest exposure is in bold.

6.0 Residential and Non-Occupational Exposure/Risk Characterization

Occupational and Residential Exposure Memo: D426984, 12/21/15, W. Britton.

Residential exposures (handler and post-application) are anticipated from the use of TCVP pet 

products for dogs and cats (collars, dusts/powders, and pump/trigger sprays). Exposures are 

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

for adults and children who may contact previously treated pets. 

Updates to the Residential Assessment: The most recent residential risk assessment for TCVP 

was completed in November 2014 (W. Britton, 11/05/14, D420283). The current TCVP human 

health risk assessment takes into account, where appropriate, comments from NRDC in their 

August 5, 2015 Opening Brief to the U.S. Court of Appeals of the 9th Circuit, which was filed as 

a result of the 2014 residential assessment and EPA’s subsequent denial of the NRDC petition to 

cancel all TCVP pet products. The current assessment also reflects the following changes from 

the 2014 residential assessment:

 LOCs for incidental oral and inhalation exposures have been revised to reflect 

inclusion of the 10X FQPA safety factor. 

 There is no non-cancer dermal hazard for TCVP.

 A female-specific body weight, 69 kg, is used for assessment of adult exposures 

instead of the average adult body weight of 80 kg (more detailed information 

provided below).

 Use of newer pet residue transfer data for pet collars that result in more conservative 

estimates of residue transfer/exposure than the data used in the 2014 risk assessment. 
Page 46 of 152

Residential assessments are performed using data from two recently submitted pet 

collar residue transfer studies (the amitraz study and the Davis study; more detailed 

information provided below).

 The exposures to TCVP pet collar products are assessed assuming collars may be a 

liquid formulation or a dust formulation (more detailed information provided below).

Body Weight Assumptions: For adults, when an endpoint is not sex-specific (i.e., the endpoints 

are based on developmental or fetal effects) a body weight of 80 kg is typically used in risk 

assessment. However, for the OP chemical class, a female-specific body weight of 69 kg is now 

assumed for adults. While the endpoint of concern, RBC AChE inhibition, is not sex-specific, 

the female body weight is used in the TCVP residential assessments, as for the other OP 

assessments, for adults due to concerns for potentially pregnant women. A body weight of 11 kg 

was assumed for children (1 to < 2 years old). The lifestages selected for each residential 

scenario (i.e., adults (female body weight) and children 1 to < 2 years old) are health protective 

for the exposures and risk estimates for any other potentially exposed lifestage.

Residue Data Assumptions: Several sources of data were used in the current residential

assessment. Similar to the 2014 assessment, these include the 2012 Residential SOPs (Treated 

Pets), a TCVP dust/powder applicator exposure study (MRID 45519601), and a TCVP dust and 

pump spray study (MRID 45485501). For assessment of post-application exposure to pet 

collars, different pet fur residue transfer studies have been used in the current assessment 

compared to the 2014 assessment. In the 2014 assessment, a propoxur pet collar study (MRID 

448589901) was used; however, in the current assessment, both an amitraz pet collar residue 

transfer study (MRID 49468801), and a literature study using TCVP pet collars (the Davis 

study)11 were used. These studies have been chosen for use in the current risk assessment as they 

provide higher estimates of residue transfer resulting in a more conservative exposure 

assessment.

Exposure/risk estimates are provided using residue transfer data from both the amitraz and Davis 

pet collar studies since the Davis has yet to undergo review by the HSRB. The EPA intends to 

present the Davis study at the next meeting of the HSRB, which is scheduled for January 12-13, 

2016. If the HSRB concludes that the Davis study does not constitute a human study and is 

scientifically valid, then EPA can rely on these data for regulatory risk decision making. 

Alternatively, if HSRB concludes the Davis study constitutes a human study, then under 40 CFR 

§26.1706, OPP is required to provide an opportunity for public comment and publish a full 

explanation of its decision to rely on the otherwise unacceptable data, including a thorough 

review of the ethical deficiencies of the underlying research and the full rationale for finding that 

reliance on the data is crucial to imposing a more stringent regulatory restriction. Until such 

time that these data have undergone HSRB review, post-application risk estimates for exposures 

to pet collar treated pets are to be considered preliminary and are presented for purposes of 

comparison only. 

 

11 Davis, M. et. al., Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the 

Organophosphorus Insecticide Tetrachlorvinphos. Journal of Exposure Science and Environmental Epidemiology. 

(2008) 18, 564-57)
Page 47 of 152

EPA has conducted an ethics and science review of the Davis study. The OPP-internal review of 

the applicable human ethical standards (as outlined in 40 CFR Part 26, Subpart Q) has been 

conducted and concluded that “there is no clear or convincing evidence that the conduct of the 

Davis study was fundamentally unethical; that is, the research was not intended to harm the

participants and did not fail to obtain informed consent. Similarly, the conduct of the study was 

not deficient relative to the ethical standards prevailing at the time the research was conducted; 

the studies did not place participants at increased risk of harm (based on knowledge available at 

the time the study was conducted) or impair their informed consent.” 12 The ethics review also 

states that, “OPP wishes to rely on the TCVP glove residue data generated. The data may be 

crucial to a potential EPA decision to improve public health protection by imposing a more 

stringent regulatory restriction than could be justified without the data. If EPA proceeds under 

§26.1706, EPA needs to obtain the views of the Human Studies Review Board, provide an 

opportunity for public comment, and publish a full explanation of its decision to rely on the data, 

including a thorough discussion of the ethical deficiencies of the underlying research and the full 

rationale for finding that EPA met the standard in 40 CFR §26.1706 (c) (i.e., that the research is 

essential to a more stringent regulatory action to improve protection of public health).”

The OPP-internal science review for the Davis study13 has concluded that the methods used for 

conduct of the collection of transferable TCVP residues from petting/rubbing of the dogs treated 

with TCVP pet collars are scientifically valid. In addition to the transferable residue data, the 

Davis study also includes 1) plasma cholinesterase (ChE) from treated dogs 2) T-shirt samples 

collected from children exposed to TCVP treated dogs and 3) urinary biomonitoring for adults 

and children exposure to TCVP treated dogs. For purposes of the TCVP risk assessment, EPA 

may rely only on the transferable residue data as these are the only data from the study that result 

in the potential for greater risks, are applicable to human exposures (in the case of the dog 

plasma ChE measures), or in the case of the urinary biomonitoring data, are useful given current 

scientific limitations (i.e., a physiologically based pharmacokinetic (PBPK) model applicable to 

TCVP). 

Table 6.1 below provides a summary of the studies considered for the residue transfer input.

Table 6.1. Summary of Pet Collar Residue Transfer Studies and Assumptions for use in TCVP Residential Assessment

Residue 

Transfer Study

Used in Current 

Risk Assessment Methodology

Non-Cancer 

Residue Transfer 

Assumption

Cancer Residue 

Transfer Assumption

Propoxur pet 

collar1 No (used in 2014) Twenty petting simulations to treated dogs. Each simulation 

consisted of three strokes (60 

strokes total) conducted using a 

mannequin hand fitted with cotton 

gloves over top of a nitrile glove

0.072% 

(mean Day 0)

0.013% 

(mean over 28 days)

Amitraz pet 

collar2 Yes 0.14% (mean Day 0)

0.047% 

(mean over 28 days)

Davis pet collar3 Yes

Dogs were petted by volunteers 

continuously for a 5 minute period 

with use of cotton glove in 

0.40% 

(mean Day 12)

0.3% 

(mean over 112 days)

 

12 M. Lydon. Ethics Review of Davis et al Research on Flea Collars with TCVP. 12/15/2015. 

13 W. Britton. Science Review of “Davis et al., 2008. Assessing Intermittent Pesticide Exposure from Flea Control 

Collars Containing the Organophosphorus Insecticide Tetrachlorvinphos” for HSRB Consideration. D430707. 

12/16/2015. 
Page 48 of 152

Table 6.1. Summary of Pet Collar Residue Transfer Studies and Assumptions for use in TCVP Residential Assessment

Residue 

Transfer Study

Used in Current 

Risk Assessment Methodology

Non-Cancer 

Residue Transfer 

Assumption

Cancer Residue 

Transfer Assumption

following with a defined rubbing 

protocol

1. MRID 448589901: Determination of Transferable Residues of Propoxur from the Hair of Dogs Wearing collars Impregnated with Propoxur –

Final Report.

2. MRID 49468801: Determination of Transferable Residues of Amitraz from the Hair of Dogs Following the Application of the Preventic® 

Collar.

3. Davis, M. et. al., Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the Organophosphorus Insecticide 

Tetrachlorvinphos. Journal of Exposure Science and Environmental Epidemiology. (2008) 18, 564-57)

Pet Collar Formulation Assumptions: Per the 2012 Residential SOPs, Treated Pets, pet collar 

products have been categorized as a liquid formulation. This assertion was based on research 

conducted at the time of SOP development that supported that pet collars function by means of 

diffusion, transferring from the collar to the surrounding area. More specifically, the active 

ingredient, which is embedded in the collar matrix, diffuses slowly through the matrix, thus 

controlling the amount of the active ingredient at the collar’s surface. The active ingredient 

available on the surface of the pet collar then “rubs off” or transfers from the collar to the 

animal’s hair coat via embedded lubricants which function like transfer agents at the surface of 

the collar. However, the NRDC asserts that TCVP pet collars are a solid formulation since a 

TCVP collar product (EPA Reg. No. 2596-84) states that “as the collar begins to work, a fine 

white powder will appear on the surface.” HED has confirmed this statement is present on the 

current labeling for the identified product and that an identical statement is also found on the 

following TCVP pet collar products (5 of 9 total pet collar products): EPA Reg. Nos. 2596-62, 

2596-63, 2596-83, 2596-84, and 2596-139. Taking into account these label statements, and 

based upon further research which suggests that that some pet collars may act by extrusion of the 

active ingredient from the collar matrix as a fine dust, HED has reconsidered the position that the 

TCVP pet collars are all liquid formulated products. At this time, HED has not received 

confirmation from the TCVP pet product registrants regarding whether the pet collars are 

designed to release the active ingredient in a dust or liquid form. Because there remains

uncertainty around whether the TCVP pet collars are liquid or solid formulations, the collar 

products are assessed here as both a liquid formulation and as a solid (dust) formulation. Until 

the formulation types of the registered TCVP pet collar products can be determined, any risk 

results or conclusions regarding exposures to the collars may be considered preliminary.

6.1 Residential Handler Exposure

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. Both non-cancer (steady state) and cancer 

residential handler exposure assessments were performed for adult homeowners applying TCVP 

pet collars, dusts/powders, and pump/trigger spray products to cats and dogs. Since there is no 

non-cancer dermal hazard for TCVP, the non-cancer handler assessment includes only 

inhalation exposures. For the cancer assessment, both dermal and inhalation exposures are 
Page 49 of 152

assessed.

For handlers, when assuming the TCVP pet collars are a liquid formulation, the liquid-specific 

unit exposure (UE) values (i.e., surrogate data from spot-on applicator study) from the 2012 

Residential SOPs were used. When assuming the pet collars are a solid formulation, HED used 

the best available data, a TCVP dust/powder applicator exposure study (MRID 45519601).

TCVP-specific handler exposure data are not available for the dust/powder and pump/trigger 

spray formulations. Those handler scenarios are assessed using the 2012 Residential SOPs

surrogate data.

Residential Handler Non-Cancer Exposure and Risk Estimates

The exposure data and assumptions that underlie the residential handler non-cancer risk 

estimates can be found in the occupational and residential exposure (ORE) memo (D426984) and 

the 2012 Residential SOPs. The algorithms used to estimate non-cancer exposure and dose for 

residential handlers can be found in Appendix D of D426984 and/or the 2012 Residential SOPs.

Summary of Residential Handler Non Cancer Exposure and Risk Estimates:

Dust/Powder and Pump/Trigger Spray: All residential handler (adults) non-cancer 

(steady state) inhalation risks estimated for the TCVP pet dust/powder and pump/trigger 

spray formulations are not of concern (i.e., all MOEs are > 300; LOC=300). 

Pet Collars: Assuming that all TCVP pet collars are solid (dust) formulations, all 

residential handler (adults) non-cancer inhalation risks estimated are not of concern (i.e., 

all MOEs are > 300; LOC=300). Assuming that all TCVP pet collars are liquid 

formulations, the application of the collars are expected to result in negligible inhalation 

exposure; therefore, there are no non-cancer risks of concern for handlers applying 

TCVP collars as liquid formulations.

A summary of residential handler exposures and risks is presented in Appendix F. 

Residential Handler Cancer Exposure and Risk Estimates

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 exposure data and assumptions that underlie the residential handler cancer risk estimates can 

be found in the ORE memo (D426984) and the 2012 Residential SOPs. The algorithms used to 

estimate the LADD and cancer risk for residential handlers can be found in Appendix D of 

D426984.
Page 50 of 152

Summary of Residential Handler Cancer Exposure and Risk Estimates

Dust/Powder and Pump/Trigger Spray: Residential handler cancer risks (inhalation and 

dermal combined) estimated for TCVP dusts/powders range from 10-8to 10-7, and for 

pump/trigger sprays range from 10-9to 10-8. 

Pet Collars: Residential handler cancer risks (inhalation and dermal combined) 

estimated for TCVP pet collars are all in the 10-8range when assuming a liquid 

formulation and are all in the 10-7range when assuming a dust formulation. 

A summary of residential handler cancer exposures and risks is presented in Appendix G. 

6.2 Residential Post-Application Exposure

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

contacting a cat or dog previously treated with TCVP pet products (dusts/powders, pump/trigger 

sprays, pet collars). The quantitative exposure/risk assessment for residential post-application 

exposures is based on the following scenarios:

1) Post-application cancer dermal (adults) exposure from contacting cats and dogs treated with 

TCVP; and 

2) Post-application non-cancer incidental oral (hand-to-mouth) exposure (children 1 to < 2 year 

olds) from contacting cats and dogs treated with TCVP.

Since there is no non-cancer dermal hazard for TCVP, the non-cancer post-application 

assessment would include only inhalation (adult and child) and incidental oral (child) 

exposures. However, a quantitative residential post-application inhalation exposure assessment 

was not performed as inhalation exposure is expected to be negligible from contact with treated

pets. An inhalation exposure assessment was performed for occupational pet handlers (i.e., 

veterinarians, veterinary assistants, and groomers) and this exposure scenario is considered 

protective of any potential low-level post-application inhalation exposure that could result from 

these types of uses (see Section 8.0 below). For the adult cancer post-application assessment, 

only dermal exposures are quantitatively assessed.

Non-Cancer Post-application Assessment

Residential Non-Cancer Post-Application Exposure Data and Assumptions

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

cancer post-application risk assessment. More detailed information about the exposure data and 

assumptions that underlie the residential post-application cancer risk estimates can be found in 

D426984. 

Residue Transfer Assumptions: Surrogate and chemical-specific residue transfer studies were 

used for assessment of non-cancer post-application exposures from registered TCVP pet 

products.
Page 51 of 152

For dusts/powders and pump/trigger sprays, the maximum residue transfers of 0.048% and 

0.81% respectively were used from a TCVP powder and pump spray study (MRID 45485501) 

was used. As described in the 2014 residential risk assessment, 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. In 

order to account for the differences between the TCVP powder and pump spray 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 post-application 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 post-application exposure study methods have 

evolved, the TCVP study employed a rigorous collection method and is not anticipated to 

underestimate exposure. 

For pet collars, in conjunction with the 2012 SOPs, data from the amitraz study and the Davis 

study were used (see Table 6.1). For the non-cancer post-application assessment of TCVP 

collars, the mean residue transfers of 0.14% (amitraz study; day 0 mean) and 0.40% (Davis 

study; 12 day mean) were used. Typically, Day 0 residue transfer values are used for the 

assessment of risks occurring over short- or intermediate-term, or steady state durations; 

however, the Davis study presents only a 12 day mean transferable residue value. Until the 

Davis study has undergone HSRB review, post-application risk estimates for exposure to pet 

collar treated pets are considered to be preliminary. A full description of the amitraz and Davis 

studies can be found in Section 5.3 of the ORE memo (D426984). The non-cancer and cancer 

post-application assessments for the pet collars were performed assuming pet collars could be 

either a liquid or solid formulation, and using residue transfer data from the two available studies 

(the amitraz study and the Davis study).

Residential Non-Cancer Post-application Exposure and Risk Equations

The algorithms used to estimate non-cancer exposure and dose for residential post-application 

can be found in Appendix D of D426984 and the 2012 Residential SOPs.

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

Since there is no non-cancer dermal hazard for TCVP and post-application inhalation exposures 

to treated pets are negligible, a quantitative non-cancer post-application exposure assessment was 

not performed for adults; there are no residential non-cancer risk estimates of concern for adults 

contacting pets treated with TCVP products.

Dust/Powder and Pump/Trigger Spray: For children (child 1 to < 2 years old), residential postapplication non-cancer incidental oral (hand-to-mouth) exposures to pets treated with TCVP 

pump/trigger sprays are not of concern (i.e., MOEs are > 1,000; LOC=1000). However, child 

incidental oral (hand-to-mouth) exposures to pets treated with TCVP dust/powder products are 

estimated to be of concern for 14 of 17 total exposure scenarios assessed (i.e., MOEs are < 

1,000; LOC=1000). 

Pet Collars: The post-application exposure and risk estimates for the various pet collar 

assumptions are provided below:
Page 52 of 152

Liquid formulation/Amitraz study assumption: With use of the amitraz pet collar residue 

transfer study and SOP inputs specific for liquid formulation products, residential postapplication child (1 to < 2 years) old incidental oral risk estimates for all TCVP pet 

collars are not of concern (i.e., MOEs are > 1,000; LOC=1000). 

Liquid formulation/Davis study assumption: With use of the Davis study and assuming 

collars are liquid formulations, all but 1 of the exposure scenarios assessed, 22 of 23 total, 

are not of concern (EPA Reg. No. 2596-139; exposures to a small sized dog). 

Solid formulation/Amitraz study assumption: With use of the amitraz pet collar study and 

SOP inputs specific for solid (dust) formulation products, residential post-application 

child (1 to < 2 years) old incidental oral risk estimates for all TCVP pet collars are of 

concern (i.e., MOEs are < 1,000; LOC=1000). 

Solid formulation/Davis study assumption: A quantitative post-application child 

incidental oral assessment was not performed using the Davis study and assuming the 

collars are dust formulations since the mean residue transfer measured in the Davis study 

was greater than that in the amitraz study. MOEs would be lower using the Davis study 

than when using the amitraz study. When assuming the TCVP collars are solid (dust) 

formulations, whether the amitraz study or Davis study is used, post-application child 

incidental oral risk estimates for all TCVP pet collars are of concern (i.e., MOEs are < 

1,000; LOC=1000).

A summary of residential post-application exposures and risks from TCVP pet products is 

presented in Appendix H. 

Cancer Post-application Assessment

Residential Cancer Post-Application Exposure Data and Assumptions

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

cancer post-application risk assessment. All exposure data and assumptions that underlie the 

residential post-application cancer risk estimates can be found in D426984. 

Residue Transfer Assumptions: For the cancer post-application assessment of TCVP 

dusts/powders and pump/trigger sprays, 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. Due to the reasons described above (under 

“Residential Non-Cancer Post-Application Exposure Data and Assumptions”), maximum residue 

values from the TCVP powder and pump spray study were used for cancer post-application 

assessment. For the cancer post-application assessment of TCVP collars, the mean residue 

transfers of 0.047% (amitraz study; 28 day mean) and 0.30% (Davis study; study 1 - 112 day 

mean) were used (see Table 6.1).

Residential Cancer Post-application Exposure and Risk Estimate Equations

As was done for residential handlers, cancer post-application risk estimates for adults were 
Page 53 of 152

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 D of D426984. 

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. 

Summary of Residential Post-application Cancer Exposure and Risk Estimates

Dust/Powder and Pump/Trigger Spray: Residential post-application cancer (adult only) risks 

estimated for TCVP pump/trigger sprays range from 10-7to 10-6and, for TCVP dust/powder 

products estimated cancer risks are 10-7. 

Pet Collars: Residential post-application cancer risk estimates for the TCVP pet collar 

formulation have also been assessed with use of the exposure data and 2012 Residential SOP 

inputs as described for post-application non-cancer risks. The post-application exposure and risk 

estimates for the various pet collar assumptions are provided below:

Liquid formulation/Amitraz study assumption: With use of the amitraz pet collar residue 

data and SOP inputs specific for liquid formulations, estimated cancer (adult only) risks 

range from 10-7 to 10-6. 

Liquid formulation/Davis study assumption: With use of the Davis study and SOP inputs 

specific for liquid formulations, estimated cancer risks range from 10-6to 10-5. 

Solid formulation/Amitraz study assumption: With use of the amitraz pet collar residue 

transfer data and SOP inputs specific for dust formulations, all cancer risks are estimated 

to be 10-5.

Solid formulation/Davis study assumption: A quantitative post-application cancer 

assessment was not performed using the Davis study and assuming the collars are dust 

formulations since the mean residue transfer measured in the Davis study was greater 
Page 54 of 152

than that in the amitraz study. Cancer risk estimates would be lower using the Davis 

study than when using the amitraz study.

Adult residential post-application dermal cancer risk estimates are presented in Appendix I. 

6.3 Non-Occupational Spray Drift Exposure and Risk Estimates

A quantitative spray drift assessment was not conducted because the use of TCVP for direct 

animal treatment to livestock and their premises, in kennels, outdoors as a perimeter treatment, 

and as a flea treatment on cats and dogs are either 1) not applied via aircraft, groundboom, or 

airblast equipment or 2) for applications to poultry buildings with groundboom equipment, the 

use is indoors and not anticipated to be a significant source of significant source of spray drift. 

6.4 Residential Bystander Post-Application Inhalation Exposure

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

inhalation exposure is expected to be negligible from applications to pets. However, an 

inhalation exposure assessment was performed for handlers (i.e., veterinarians, veterinary 

assistants, and groomers) and this exposure scenario should be considered protective of any 

potential low-level post-application inhalation exposure that could result from these types of 

applications. There are no post-application inhalation risks of concern.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, when there are potential residential exposures to a pesticide, 

aggregate risk assessment must consider exposures from three major routes: oral, dermal, and 

inhalation. There are three sources for these types of exposures: food, drinking water, and 

residential uses. In an aggregate assessment, exposures from relevant sources are added together 

and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks 

themselves can be aggregated. When aggregating exposures and risks from various sources, 

HED considers both the route and duration of exposure.

7.1 Acute Aggregate Risk

The acute aggregate risk assessment combines exposures to TCVP from food and drinking water. 

There are no acute aggregate risk estimates of concern for (see Section 5.4.3 Acute Dietary 

Assessment).

7.2 Steady State Aggregate Risk

There is a potential for steady state exposure to TCVP via dietary and residential exposure 

pathways. The steady state aggregate risk assessment combines steady state exposures from 

food, drinking water, and residential (pet product) uses. Steady state aggregate risk assessments 

were performed for adult handlers (females, age 13-49 years) applying registered pet collars, 

dust/powders, and pump/trigger spray products to cats and dogs. Residential post-application 
Page 55 of 152

steady state aggregate risk assessments were also performed for children (age 1-2) contacting 

pets that have been treated with the collar, dust/powder, and pump/trigger spray products.

Residential Handler Noncancer Steady State Aggregate

Table 7.2.1 below shows the steady state aggregate risk estimates for the residential handler 

scenarios. Since there is no dermal hazard for TCVP, the residential exposure consists of only 

inhalation for the adult handler. An Aggregate Risk Index (ARI) approach was used to aggregate 

the steady state dietary and residential exposures since the levels of concern are not the same for 

those exposures (1000 and 300, respectively).

Residential handler steady state aggregate (food, water, residential) risk estimates for all 

registered TCVP pet product scenarios (collars, dust/powders, pump/trigger sprays) are not of 

concern (ARIs ≥ 1).

Table 7.2.1 TCVP Noncancer (Steady State) Residential Handler AGGREGATE Risk Calculations for 

ADULTS 1

EPA Reg. 

No/Animal

Animal Size

(or collar size 

in grams)

Residential Handler Aggregate

Dietary Exposure 2

Inhalation Residential 

Exposure3

Aggregate ARI 

(food, water, and 

residential; 

LOC = 1)

4

MOE

(LOC = 1000)

ARI

(LOC = 1)

MOE

(LOC = 300)

ARI

(LOC = 1)

Pet Collars (Liquid Assumption): 2012 Residential SOPs (Spot-on Surrogate Data)

2596-49; Cat 11g 5,100 5.1 N/A5 N/A 5.1

2596-50, 62: 

Dog

19g 5,100 5.1 N/A N/A 5.1

32g 5,100 5.1 N/A N/A 5.1

2596-83: Cat

12g 5,100 5.1 N/A N/A 5.1

25g 5,100 5.1 N/A N/A 5.1

2596-139: 

Cat 10g 5,100 5.1 N/A N/A 5.1

11556-164: 

Dog 24g 5,100 5.1 N/A N/A 5.1

11556-165: 

Cat 15g 5,100 5.1 N/A N/A 5.1

2596-84: Dog

19g 5,100 5.1 N/A N/A 5.1

32g 5,100 5.1 N/A N/A 5.1

2596-139: 

Dog 50g 5,100 5.1 N/A N/A 5.1

2596-63: Cat

15g 5,100 5.1 N/A N/A 5.1

17g 5,100 5.1 N/A N/A 5.1

Pet Collars (Solid Assumption): TCVP Dust/Powder Applicator Study (MRID 45519601)

2596-49; Cat 11g 5,100 5.1 4900 16 3.9

2596-50, 62: 

Dog

19g 5,100 5.1 2900 9.7 3.3

32g 5,100 5.1 1700 5.7 2.7

2596-83: Cat

12g 5,100 5.1 4600 15 3.8

25g 5,100 5.1 2200 7.3 3.0

2596-139: 

Cat 10g 5,100 5.1 4600 15 3.8
Page 56 of 152

Table 7.2.1 TCVP Noncancer (Steady State) Residential Handler AGGREGATE Risk Calculations for 

ADULTS 1

EPA Reg. 

No/Animal

Animal Size

(or collar size 

in grams)

Residential Handler Aggregate

Dietary Exposure 2

Inhalation Residential 

Exposure3

Aggregate ARI 

(food, water, and 

residential; 

LOC = 1)

4

MOE

(LOC = 1000)

ARI

(LOC = 1)

MOE

(LOC = 300)

ARI

(LOC = 1)

11556-164: 

Dog 24g 5,100 5.1 2500 8.3 3.2

11556-165: 

Cat 15g 5,100 5.1 3900 13 3.7

2596-84: Dog

19g 5,100 5.1 2900 9.7 3.3

32g 5,100 5.1 1700 5.7 2.7

2596-139: 

Dog 50g 5,100 5.1 1100 3.7 2.1

2596-63: Cat

15g 5,100 5.1 3700 12 3.6

17g 5,100 5.1 3300 11 3.5

Dust/Powder : TCVP Dust/Powder Applicator Study (MRID 45519601)

4700-123: 

Dog

small 5,100 5.1 47,000 160 4.9

medium 5,100 5.1 19,000 63 4.7

large 5,100 5.1 12,000 40 4.5

47000-123: 

Cat

small 5,100 5.1 190,000 630 5.1

medium 5,100 5.1 79,000 260 5.0

large 5,100 5.1 53,000 180 5.0

2596-78: Cat

small 5,100 5.1 29,000 97 4.8

large 5,100 5.1 17,000 57 4.7

2596-79: Dog

small 5,100 5.1 17,000 57 4.7

medium 5,100 5.1 8,600 29 4.3

large 5,100 5.1 6,900 23 4.2

67517-82: 

Dog

small 5,100 5.1 16,000 53 4.7

medium 5,100 5.1 6,300 21 4.1

large 5,100 5.1 3,900 13 3.7

67517-82: 

Cat

small 5,100 5.1 63,000 210 5.0

medium 5,100 5.1 26,000 87 4.8

large 5,100 5.1 18,000 60 4.7

Pump/Trigger Spray: 2012 Residential SOPs (Surrogate Data)

2596-

126,140: Cat 

(trigger)

small 5,100 5.1 30,000 100 4.9

large 5,100 5.1 22,000 73 4.8

2596-140: 

Cat (pump)

small 5,100 5.1 150,000 500 5.0

large 5,100 5.1 110,000 370 5.0

2596-125, -

140: Dog 

(trigger)

small 5,100 5.1 22,000 73 4.8

medium 5,100 5.1 19,000 63 4.7

large 5,100 5.1 11000 37 4.5

1 HED is concerned if the ARI is less than 1. (ARI = Aggregate Risk Index.) ARIs<1 are Bolded.

2 MOE dietary = [(Steady State BMDL10)/(chronic dietary exposure)]. ARI dietary = [(MOE dietary)/(MOE 

target)]. BMDL10=8.0 mg/kg day; Target MOE=LOC=1000. 
Page 57 of 152

3 MOE inhalation = [(Steady State HED)/( inhalation residential exposure)]. ARI inhalation = [(MOE 

inhalation)/(MOE target)]. HED=1.59 mg/kg/day; target MOE=LOC=300. 

4 ARI Aggregate = 1/[(1/ARI dietary) + (1/ARI oral) + (1/ARI dermal) + (1/ARI inhalation)]

5 N/A= not applicable, negligible inhalation exposure from liquid collars.

Residential Post-Application Steady State Aggregate

Table 7.2.2 below shows the steady state aggregate risk estimates for the residential postapplication scenarios for children contacting treated pets. Since there is no dermal hazard for 

TCVP, and post-application inhalation exposures are negligible, the residential post-application 

exposure consists of only incidental oral exposure for children.

Assuming liquid formulation and using the amitraz study, steady state post-application aggregate 

MOEs for children were not of concern (MOEs > 1000) for all 23 pet collar scenarios. Assuming 

liquid formulation and using the Davis study, 8 of the 23 scenarios resulted in aggregate MOEs 

of concern. Assuming solid formulation and using the amitraz study, all 23 scenarios resulted in 

aggregate MOEs of concern. Quantitative assessments were not presented assuming solid 

formulation and the Davis study; those MOEs would be even lower than for the solid/amitraz 

assessments.

For the TCVP dust/powder pet products, the steady state post-application aggregate assessments 

resulted in 16 of the 17 scenarios with risk estimates of concern (MOEs < 1000).

For all TCVP and pump/trigger spray product scenarios, steady state post-application aggregate 

risk estimates are not of concern.

Table 7.2.2 TCVP Noncancer (Steady State) Residential Post-Application AGGREGATE Risk Calculations for 

CHILDREN

EPA Reg. 

No/Animal

Animal 

Size

Residential Post-Application Aggregate

BMDL10

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure

(Incidental 

Oral)

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Pet Collars (Liquid Assumption): Amitraz Exposure Data (MRID 49468801)

2596-49:

Cat

small 8.0 1000 0.008 0.003273 0.002 0.005273 1500

medium 8.0 1000 0.008 0.003273 0.0012 0.004473 1800

large 8.0 1000 0.008 0.003273 0.00074 0.004013 2000

2596-50, 62: 

Dog

small 8.0 1000 0.008 0.003273 0.0016 0.004873 1600

large 8.0 1000 0.008 0.003273 0.00076 0.004033 2000

2596-83:

Cat

small 8.0 1000 0.008 0.003273 0.0021 0.005373 1500

large 8.0 1000 0.008 0.003273 0.0016 0.004873 1600

2596-139: Cat

small 8.0 1000 0.008 0.003273 0.0017 0.004973 1600

medium 8.0 1000 0.008 0.003273 0.001 0.004273 1900

large 8.0 1000 0.008 0.003273 0.00065 0.003923 2000

small 8.0 1000 0.008 0.003273 0.0019 0.005173 1500
Page 58 of 152

Table 7.2.2 TCVP Noncancer (Steady State) Residential Post-Application AGGREGATE Risk Calculations for 

CHILDREN

EPA Reg. 

No/Animal

Animal 

Size

Residential Post-Application Aggregate

BMDL10

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure

(Incidental 

Oral)

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

11556-164: 

Dog

medium 8.0 1000 0.008 0.003273 0.00084 0.004113 1900

large 8.0 1000 0.008 0.003273 0.00053 0.003803 2100

11556-165: 

Cat

small 8.0 1000 0.008 0.003273 0.0024 0.005673 1400

medium 8.0 1000 0.008 0.003273 0.0015 0.004773 1700

large 8.0 1000 0.008 0.003273 0.00092 0.004193 1900

2596-84:

Dog

small 8.0 1000 0.008 0.003273 0.0016 0.004873 1600

large 8.0 1000 0.008 0.003273 0.00076 0.004033 2000

2596-139: Dog

small 8.0 1000 0.008 0.003273 0.0043 0.007573 1000

medium 8.0 1000 0.008 0.003273 0.0019 0.005173 1500

large 8.0 1000 0.008 0.003273 0.0012 0.004473 1800

2596-63:

Cat

small 8.0 1000 0.008 0.003273 0.0026 0.005873 1400

large 8.0 1000 0.008 0.003273 0.0011 0.004373 1800

Pet Collars (Liquid Assumption): TCVP/Davis Study

2596-49:

Cat

small 8.0 1000 0.008 0.003273 0.0056 0.008873 900

medium 8.0 1000 0.008 0.003273 0.0033 0.006573 1200

large 8.0 1000 0.008 0.003273 0.0021 0.005373 1500

2596-50, 62: 

Dog

small 8.0 1000 0.008 0.003273 0.0047 0.007973 1000

large 8.0 1000 0.008 0.003273 0.0021 0.005373 1500

2596-83:

Cat

small 8.0 1000 0.008 0.003273 0.0059 0.009173 870

large 8.0 1000 0.008 0.003273 0.0046 0.007873 1000

2596-139: Cat

small 8.0 1000 0.008 0.003273 0.0049 0.008173 980

medium 8.0 1000 0.008 0.003273 0.003 0.006273 1300

large 8.0 1000 0.008 0.003273 0.0018 0.005073 1600

11556-164: 

Dog

small 8.0 1000 0.008 0.003273 0.0055 0.008773 910

medium 8.0 1000 0.008 0.003273 0.0024 0.005673 1400

large 8.0 1000 0.008 0.003273 0.0015 0.004773 1700

11556-165: 

Cat

small 8.0 1000 0.008 0.003273 0.0069 0.010173 790

medium 8.0 1000 0.008 0.003273 0.0042 0.007473 1100

large 8.0 1000 0.008 0.003273 0.0026 0.005873 1400

2596-84:

Dog

small 8.0 1000 0.008 0.003273 0.0047 0.007973 1000

large 8.0 1000 0.008 0.003273 0.0021 0.005373 1500

2596-139: Dog

small 8.0 1000 0.008 0.003273 0.012 0.015273 520

medium 8.0 1000 0.008 0.003273 0.0053 0.008573 930

large 8.0 1000 0.008 0.003273 0.0034 0.006673 1200

2596-63:

Cat

small 8.0 1000 0.008 0.003273 0.0074 0.010673 750

large 8.0 1000 0.008 0.003273 0.0031 0.006373 1300
Page 59 of 152

Table 7.2.2 TCVP Noncancer (Steady State) Residential Post-Application AGGREGATE Risk Calculations for 

CHILDREN

EPA Reg. 

No/Animal

Animal 

Size

Residential Post-Application Aggregate

BMDL10

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure

(Incidental 

Oral)

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Pet Collars (Solid Assumption): Amitraz Exposure Data (MRID 49468801)

2596-49:

Cat

small 8.0 1000 0.008 0.003273 0.49 0.493273 16

medium 8.0 1000 0.008 0.003273 0.3 0.303273 26

large 8.0 1000 0.008 0.003273 0.18 0.183273 44

2596-50, 62: 

Dog

small 8.0 1000 0.008 0.003273 0.41 0.413273 19

large 8.0 1000 0.008 0.003273 0.19 0.193273 41

2596-83:

Cat

small 8.0 1000 0.008 0.003273 0.52 0.523273 15

large 8.0 1000 0.008 0.003273 0.41 0.413273 19

2596-139: Cat

small 8.0 1000 0.008 0.003273 0.44 0.443273 18

medium 8.0 1000 0.008 0.003273 0.26 0.263273 30

large 8.0 1000 0.008 0.003273 0.16 0.163273 49

11556-164: 

Dog

small 8.0 1000 0.008 0.003273 0.49 0.493273 16

medium 8.0 1000 0.008 0.003273 0.21 0.213273 38

large 8.0 1000 0.008 0.003273 0.13 0.133273 60

11556-165: 

Cat

small 8.0 1000 0.008 0.003273 0.61 0.613273 13

medium 8.0 1000 0.008 0.003273 0.37 0.373273 21

large 8.0 1000 0.008 0.003273 0.23 0.233273 34

2596-84:

Dog

small 8.0 1000 0.008 0.003273 0.41 0.413273 19

large 8.0 1000 0.008 0.003273 0.19 0.193273 41

2596-139: Dog

small 8.0 1000 0.008 0.003273 1.1 1.103273 7

medium 8.0 1000 0.008 0.003273 0.47 0.473273 17

large 8.0 1000 0.008 0.003273 0.3 0.303273 26

2596-63:

Cat

small 8.0 1000 0.008 0.003273 0.65 0.653273 12

large 8.0 1000 0.008 0.003273 0.28 0.283273 28

Dust/Powder: TCVP Dust and Pump Spray Study (MRID 45485501)

4700-123: Dog

small 8.0 1000 0.008 0.003273 0.0087 0.011973 670

medium 8.0 1000 0.008 0.003273 0.0093 0.012573 640

large 8.0 1000 0.008 0.003273 0.0095 0.012773 630

47000-123: 

Cat

small 8.0 1000 0.008 0.003273 0.0043 0.007573 1000

medium 8.0 1000 0.008 0.003273 0.0063 0.009573 840

large 8.0 1000 0.008 0.003273 0.0059 0.009173 870

2596-78:

Cat

small 8.0 1000 0.008 0.003273 0.029 0.032273 250

large 8.0 1000 0.008 0.003273 0.018 0.021273 380

2596-79:

Dog

small 8.0 1000 0.008 0.003273 0.024 0.027273 290

medium 8.0 1000 0.008 0.003273 0.021 0.024273 330

large 8.0 1000 0.008 0.003273 0.016 0.019273 420
Page 60 of 152

Table 7.2.2 TCVP Noncancer (Steady State) Residential Post-Application AGGREGATE Risk Calculations for 

CHILDREN

EPA Reg. 

No/Animal

Animal 

Size

Residential Post-Application Aggregate

BMDL10

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure

(Incidental 

Oral)

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

67517-82: Dog

small 8.0 1000 0.008 0.003273 0.026 0.029273 270

medium 8.0 1000 0.008 0.003273 0.028 0.031273 260

large 8.0 1000 0.008 0.003273 0.028 0.031273 260

67517-82: Cat

small 8.0 1000 0.008 0.003273 0.013 0.016273 490

medium 8.0 1000 0.008 0.003273 0.019 0.022273 360

large 8.0 1000 0.008 0.003273 0.018 0.021273 380

Pump/Trigger Spray: TCVP Dust and Pump Spray Study (MRID 45485501)

2596-126,140: 

Cat (trigger)

small 8.0 1000 0.008 0.003273 0.0017 0.004973 1600

large 8.0 1000 0.008 0.003273 0.0009 0.004173 1900

2596-140: Cat 

(pump)

small 8.0 1000 0.008 0.003273 0.00035 0.003623 2200

large 8.0 1000 0.008 0.003273 0.00018 0.003453 2300

2596-125, -

140: Dog 

(trigger)

small 8.0 1000 0.008 0.003273 0.0012 0.004473 1800

medium 8.0 1000 0.008 0.003273 0.00059 0.003863 2100

large 8.0 1000 0.008 0.003273 0.00066 0.003933 2000

1 LOC = 1000 (10X inter- and 10X intra- species uncertainty factors plus 10X FQPA SF) 

2 Maximum Allowable Exposure (mg/kg/day) = BMDL10/LOC

3 Residential Exposure = Oral exposure only (Appendix H).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5 Aggregate MOE = [BMDL10 / Total Exposure]; Aggregate MOEs < 1000 (LOC) are BOLDED

7.3 Cancer Aggregate Risk

The cancer aggregate risk assessment combines residential and dietary (food and drinking water) 

expected lifetime exposures for adults. For TCVP, a cancer aggregate assessment was performed 

for adult handlers and adult post-application activities related to pet product use.

The residential exposure for use in the cancer handler assessment is the combined dermal and 

inhalation exposures from applying TCVP products to pets (collars, dust/powders, and 

pump/trigger sprays). 

All pet product scenarios (collars, dust/powders, and pump/trigger sprays) result in residential 

handler cancer aggregate (residential and dietary) risk estimates in the 10-6range. 

All dust/powder and pump/trigger spray product scenarios result in residential post-application 

cancer aggregate (residential and dietary) risk estimates in the 10-6range. When collars are 

assumed to be liquid formulations, post-application cancer aggregate risk estimates aren the 10-6

range using the amitraz data and are 10-5to 10-6 when using the Davis data. For the solid 

formulation assumption, only the amitraz data were presented and those cancer aggregate risk 

estimates are in the 10-5 range (cancer aggregate risk estimate values would be lower if using the 
Page 61 of 152

Davis).

 

Table 7.3.1. Range of Adult Handler Aggregate Cancer Risk Estimates for TCVP Pet Products 

(Risk is estimated using a Q* of 0.00183)

Relative 

ExposureAll 

Products

Reg No.; Animal type; 

Animal size

Food and Water 

Exposure 

(mg/kg/day)1

Residential 

Exposure (LADD, 

mg/kg/day)2

Aggregate Cancer 

Risk (food, water, 

residential)

Pet Collars (Liquid Assumption): 2012 Residential SOPs (Spot-on Surrogate Data)

Lowest 2596-139; Cat; Any 5.66 x 10-4 7.5 x 10-6 1 x 10-6

Highest 2596-139; Dog; Any 5.66 x 10-4 3.8 x 10-5 1 x 10-6

Pet Collars (Solid Assumption): TCVP Dust/Powder Applicator Study (MRID 45519601)

Lowest 2596-139; Cat; Any 5.66 x 10-4 1.1 x 10-4 1 x 10-6

Highest 2596-139; Dog; Any 5.66 x 10-4 5.4 x 10-4 2 x 10-6

Dust/Powder: TCVP Dust/Powder Applicator Study (MRID 45519601)

Lowest 47000-123; Cat; Small 5.66 x 10-4 4.7 x 10-6 1 x 10-6

Highest 67517-82; Dog; Large 5.66 x 10-4 2.3 x 10-4 1. x 10-6

Pump/Trigger Spray: 2012 Residential SOPs (Surrogate Data)

Lowest 2596-140; Cat; Small (Pump) 5.66 x 10-4 2.8 x 10-6 1 x 10-6

Highest 2596-125, -140; Dog; Large 

(Trigger) 5.66 x 10-4 3.9 x 10-5 1 x 10-6

1 Table 5.4.5.1

2 Appendix G.

3Aggregate Cancer Risk = (Q1*) (Food & Water Exposure + LADD)

Table 7.3.2. Range of Adult Post-Application Aggregate Cancer Risk Estimates for TCVP Pet Products 

(Risk is estimated using a Q* of 0.00183)

Relative 

ExposurePet Products

Reg No., Animal type, Animal 

size

Food and Water 

Exposure 

(mg/kg/day)1

Residential Exposure 

(LADD, mg/kg/day)2

Aggregate Cancer 

Risk (food, water, 

residential)

Pet Collars (Liquid Assumption): Amitraz Exposure Data (MRID 49468801)

Lowest 11556-164, Dog, Large 5.66 x 10-4 2.5 x 10-4 1 x 10-6

Highest 2596-139, Dog, Small 5.66 x 10-4 2.0 x 10-3 5 x 10-6

Pet Collars (Liquid Assumption): TCVP/Davis Study

Lowest 

2596-49, Cat, Large; 

2596-50, -62, Dog, Large;

2596-84, Dog, Large

5.66 x 10-4 2.2 x 10-

3 5 x 10-6

Highest 2596-139, Dog, Small 5.66 x 10-4 1.3 x 10-2 2 x 10-5

Pet Collars (Solid Assumption): Amitraz Exposure Data (MRID 49468801)

Lowest 11556-164, Dog, Large 5.66 x 10-4 6.6 x 10-3 1 x 10-5

Highest 2596-139, Dog, Small 5.66 x 10-4 5.4 x 10-2 1 x 10-5

Dust/Powder: TCVP Dust and Pump Spray Study (MRID 45485501)

Lowest 4700-123, Cat, Small 5.66 x 10-4 2.9 x 10-4 2 x 10-6

Highest 67517-82, Dog, Medium/Large 5.66 x 10-4 1.9 x 10-3 4 x 10-6

Pump/Trigger Spray: TCVP Dust and Pump Spray Study (MRID 45485501)

Lowest 2596-140, Cat, Large (Pump) 5.66 x 10-4 5.6 x 10-5 1 x 10-6

Highest 2596-140, Cat, Small (Pump) 5.66 x 10-4 1.1 x 10-4 1 x 10-6

1 Table 5.4.5.1

2 Appendix I

3Aggregate Cancer Risk = (Q1*) (Food & Water Exposure + LADD)
Page 62 of 152

8.0 Occupational Exposure/Risk Characterization

Occupational and Residential Exposure Memo: DP#426984, 12/21/15, W. Britton.

8.1 Occupational Handler Exposure/Risk Estimates (Non-Cancer and Cancer)

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

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

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

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

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

manner specific to each application event. 

Occupational handler exposures are expected from use of TCVP on pets by veterinarians, 

veterinary assistants, and groomers. The pet use formulations include collars, dusts/powders, and 

pump and trigger sprays. Based on the anticipated use patterns and current labeling, types of 

equipment and techniques that can potentially be used, occupational handler exposure (dermal 

and inhalation) is expected.

Occupational handler exposures for the TCVP uses are anticipated to be short-term (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, non-cancer steady state exposures (21 days) were 

assessed for occupational exposures to TCVP. Only inhalation exposures were assessed for the 

steady state duration for TCVP. A quantitative dermal assessment was not performed for the 

steady state as there were no treatment related effects, including a lack of effect on RBC and 

brain cholinesterase activity, in the dermal toxicity study. A cancer assessment was also 

performed for handlers that included both inhalation and dermal exposures to TCVP.

For adults, when an endpoint is not sex-specific (i.e., the endpoints are based on developmental 

or fetal effects) a body weight of 80 kg is typically used in risk assessment. However, for the OP 

chemical class, a female-specific body weight of 69 kg is now assumed for adults. While the 

endpoint of concern, RBC AChE inhibition, is not sex-specific, the female body weight is used 

in the TCVP occupational assessments for adult workers due to concerns for potentially pregnant 

women and the uncertainties regarding neurodevelopmental effects.

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

following scenarios: 

Mixer/Loaders:

(1a) Liquid: Groundboom Applications

(1c) Liquid: Paint Applications

(2a) Wettable Powder: Groundboom Applications

(2b) Wettable Powder: Handheld Fogger Applications

(2c) Wettable Powder: Stationary Fogger Applications

(2d) Wettable Powder: Paint Applications 

(3a) Dust: Paint Applications
Page 63 of 152

Applicators:

(4) Groundboom Applications

(5) Open Pour Liquid Additive for Feed Through 

(6a) RTU Pet Collar - Liquid Formulation

(6b) RTU Pet Collar - Dust Formulation

(7) RTU Dust/Powder – Pets

(8) RTU Pump/Trigger Sprays - Pets

Mixer/Loader/Applicators:

(9a) Liquid: Backpack Sprayer

(9b) Liquid: Manually-Pressurized Handwand

(9c) Liquid: Mechanically-Pressurized Handgun

(9d) Liquid: Backrubber or Facerubber 

(10a) Wettable Powder: Backpack Sprayer

(10b) Wettable Powder: Manually-Pressurized Handwand

(10c) Wettable Powder: Mechanically-Pressurized Handgun

(10d) Wettable Powder: Handheld Fogger

(10e) Wettable Powder: Stationary Fogger

(10f) Wettable Powder: Rotary Duster

(10g) Wettable Powder: Plunger Duster

(11a) Dust: Self-Treating Dust Bag

(11b) Dust: Shaker Can 

(11c) Dust: Rotary Duster

(11d) Dust: Plunger Duster

(12a) Paint: Brush or Roller

(12b) Paint: Airless Sprayer

(13) Solid Feed Additive for Feed Through: Cup

Occupational Handler Exposure Data and Assumptions

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

include PHED 1.1, the AHETF database, and the Outdoor Residential Exposure Task Force 

(ORETF) database. 

A single chemical-specific exposure study, Monitoring Exposure of Mixer/Loaders and 

Applicators Treating Agricultural Premises with Tetrachlorvinphos (Rabon® 50 WP Insecticide) 

in Handheld Wand-Type Sprayers (MRID 42622301) was used as appropriate (i.e., exposure 

scenario 10c for mixing/loading and applying WP with mechanically-pressurized handwand) for 

the occupational risk assessment for TCVP. Risks for this exposure scenario were estimated 

with use of the chemical-specific exposure data as well as surrogate PHED data. 

The detailed exposure data and assumptions (e.g., unit exposure, area treated or amount handled, 

duration) used in the occupational handler assessment can be found in D426984 (W. Britton).
Page 64 of 152

Estimates of inhalation exposure were calculated for various levels of personal protective 

equipment (PPE). Results are presented for “baseline,” defined as a single layer of clothing 

consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no 

respirator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, 

etc). 

The PPE required for occupational use of TCVP varies by formulation type. The respiratory 

protection required for the occupational handling of TCVP can, at times, differ from label to 

label with consideration of the same formulation and exposure scenario. All but one of the 

TCVP pet product labels do not require PPE, as these are intended for residential sale as well as 

for occupational use. A summary of PPE required for all TCVP products is presented in 

Appendix L of this document.

Although occupational dermal and inhalation exposures are anticipated for TCVP, risks have 

been estimated for inhalation exposures only due to the lack of dermal hazard. Therefore, no 

combined occupational exposures/risk estimates have been quantified. 

Occupational Handler (Non-Cancer) Exposure and Risk Estimate Equations

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

found in Appendix D of D426984.

Summary of Occupational Handler Steady State (Non-Cancer) Exposure and Risk Estimates

Of the 172 total occupational handler exposure scenarios assessed, the majority (152) are not of 

concern (i.e., steady state inhalation MOEs are ≥ 300) with currently required personal protective 

equipment (PPE) (i.e., respiratory protection). Of the remaining 20 handler exposure scenarios, 

an additional 16 are not of concern with consideration of increasing levels of respiratory 

protection (i.e., four occupational handler exposure scenarios result in estimated risks of concern 

despite the addition of respiratory protection or engineering controls). These four handler 

scenarios are all dust formulations (mixing/loading/applying TCVP by rotary duster, self-treating 

dust bag, or shaker can).

A summary of all non-cancer occupational handler exposure scenarios is presented in Appendix 

J. For risk management purposes, the currently labeled level of respiratory protection and 

engineering controls has been identified (bolded) for each individual exposure scenario.

Occupational Handler Cancer Exposure and Risk Equations

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

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). 

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 
Page 65 of 152

estimate the LADD and cancer risk for occupational handlers can be found in Appendix D of 

D426984.

Summary of Occupational Handler Cancer Exposure and Risk Estimates

Occupational cancer risks were estimated for both private/farmer and contract/commercial 

handlers. Cancer risks range from 10-10 to 10-5for private/farmer handlers and from 10-10 to 10-4

for contract/commercial handlers with currently required PPE. 

Unlike the occupational handler non-cancer risk estimates which were based only on inhalation 

exposures, the occupational handler cancer risk estimates are quantified based on both dermal 

and inhalation exposures. This is because, despite the determination of the lack of dermal hazard 

for TCVP, dermal exposures from TCVP must be quantified for purpose of cancer risk 

assessment. As previously described, the PPE required for the occupational use of TCVP varies 

by formulation type. For example, for feed through (solid and liquid food additives) and feed 

blocks, occupational handlers are required to wear baseline clothing (i.e., long sleeved shirt, long 

pants, shoes and socks) and gloves. For all other end-use labels with livestock and outdoor 

perimeter uses, required PPE can vary dependent on the application type or equipment and can 

range from baseline clothing and gloves, to the addition of coveralls, or respiratory protection. 

A summary of occupational cancer risks as estimated at all levels of personal protection and with 

use of engineering controls is presented in Appendix K of D426984. Table K.1 presents cancer 

risks for private/farmer handlers and Table K.2 risks for contract/commercial handlers. For risk 

management purposes, the currently labeled level of respiratory protection and engineering 

controls has been identified (bolded) for each individual exposure scenario.

8.2 Occupational Post-application Exposure/Risk Estimates

Occupational post-application exposures are not expected as reentry activities are not anticipated 

for this use pattern. Restricted entry intervals (REIs) are not included on TCVP product labeling 

as the registered uses (i.e., livestock or other animals, or in or around animal premises) are not

covered by the Worker Protection Standard (WPS). 

9.0 Public Health and Pesticide Epidemiology Data

Incident Report Memo: DP#426986, 5/21/15, S. Recore.

HED has prepared a Tier I review of human incidents report. For this evaluation, both OPP 

Incident Data System (IDS) and the Centers for Disease Control and Prevention/National 

Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System 

for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data 

on the active ingredient TCVP. The purpose of the database search is to identify potential 

patterns in the frequency and severity of the health effects attributed to TCVP exposure. 

The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study 

evaluating the link between pesticide use and various health outcomes including cancer. TCVP 

is not included in the AHS, and therefore this study does not provide information for this report.
Page 66 of 152

Although there were a moderate number of TCVP incidents reported to Main and Aggregate IDS 

(n=374) and SENSOR-Pesticides (n=61), most of these incidents were classified as low severity. 

The effects experienced were generally minimally traumatic and resolving rapidly and usually 

involve skin, eye or respiratory irritation. Most of the reported incidents were due to handling 

and applying TCVP products to pets. Based on the low severity of incident cases reported for 

TCVP in both IDS and NIOSH SENSOR-Pesticides, there does not appear to be a concern at this 

time that would warrant further investigation. The agency will continue to monitor the incident 

information and if a concern is triggered, additional analysis will be conducted.

10.0 Cumulative Exposure/Risk Characterization

OPs, like TCVP, share the ability to inhibit AChE through phosphorylation of the serine residue 

on the enzyme leading to accumulation of acetylcholine and ultimately cholinergic neurotoxicity. 

This shared MOA/AOP is the basis for the OP common mechanism grouping per OPP’s 

Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999). The 2002 and 2006 cumulative risk assessments 

(CRAs) used brain AChE inhibition in female rats as the source of dose response data for the 

relative potency factors and PODs for each OP, including TCVP. Prior to the completion of 

registration review, OPP will update the OP CRA on AChE inhibition to incorporate new 

toxicity and exposure information available since 2006. 

As described in Section 4.4, OPP has retained the FQPA Safety Factor for OPs, including TCVP, 

due to uncertainties associated with neurodevelopmental effects in children and exposure to OPs. 

There is a lack of an established MOA/AOP for the neurodevelopment outcomes which 

precludes the agency from formally establishing a common mechanism group per the Guidance 

For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of 

Toxicity (USEPA, 1999) based on that outcome. Moreover, the lack of a recognized MOA/AOP 

and other uncertainties with exposure assessment in the epidemiology studies prevent the agency 

from establishing a causal relationship between OP exposure and neurodevelopmental outcomes. 

The agency will continue to evaluate the epidemiology studies associated with 

neurodevelopmental outcomes and OP exposure prior to the release of the revised PRA. During 

this period, the agency will determine whether or not it is appropriate to apply the draft guidance 

document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis for 

the neurodevelopment outcomes. 

11.0 EPA References

J. Abbotts, No DP#, 4/93, Results of Metabolism Committee Meeting.

F. Suhre, D199644, 7/6/94, Product Chemistry Chapter and Residue Chemistry Chapter of the 

Reregistration Decision Document.

D. Miller, 9/21/94, D206721, Addendum to RED.

D. Miller, 3/11/98, D43528, Development of Tolerance Estimates for Revised HED Chapter.
Page 67 of 152

USEPA, July 2006, Reregistration Eligibility Decision (RED).

C. Olinger, 10/7/10, D320848, D320858, D320859, and D381350, Tetrachlorvinphos. Cattle 

Oral/Dermal and Poultry Dermal Studies. Summary of Residue Data Submitted in Support of 

Reregistration.

C. Olinger, 3/25/11, D385359 and D386954, Tetrachlorvinphos. Response to Comment on 

Storage Stability Residue Data Deficiencies.

C. Olinger, 4/25/11, D320857, Tetrachlorvinphos. Request for Waiver of a Swine Magnitude of Residue 

Study.

D. Drew, 7/5/12, D396833, Tetrachlorvinphos (TCVP). Multiresidue Methods (MRM) Study of 

the Metabolites of TCVP. 

W. Britton. 11/05/14, D420283, Residential Exposure Assessment in Response to the Natural 

Resources Defense Council Petition to Cancel All Pet Uses for Tetrachlorvinphos.

C. Peck, 11/6/14, D419448, Tetrachlorvinphos (TCVP) Drinking Water Assessment for 

Registration Review.\

S. Recore, 5/21/15, D426986, Tetrachlorvinphos (TCVP): Tier I Review of Human Incidents for 

Draft Risk Assessment.

D. Drew, 10/29/15, D426985, Tetrachlorvinphos (TCVP) Acute, Steady State, and Cancer 

Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the 

Registration Review Human Health Risk Assessment.

W. Britton, 12/21/15, D426984, Tetrachlorvinphos: Occupational and Residential Exposure 

Assessment for Registration Review. 

12.0 Appendices

Appendix A. Toxicology Profile 

Appendix B. Results for BMD/BMDL modeling for TCVP 

Appendix C. Physical/Chemical Properties for Tetrachlorvinphos

Appendix D. TCVP and Metabolites

Appendix E. International MRLs and U.S. Tolerances

Appendix F. Summary of Residential Handler Non-Cancer Exposures and Risk Estimates

Appendix G. Summary of Residential Handler Cancer Exposure and Risk Estimates

Appendix H. Summary of Residential Post-Application Non-Cancer Exposure and Risk

Estimates

Appendix I. Summary of Residential Post-Application Cancer Exposure and Risk Estimates

Appendix J. Summary of Occupational Handler Non-Cancer Exposures and Risk Estimates 

Appendix K. Summary of Occupational Handler Cancer Exposures and Risk Estimates

Appendix L. Summary of TCVP Labels and Use Directions
Page 68 of 152

Appendix M. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and HumanEquivalent Doses 
Page 69 of 152

Appendix A. Toxicology Profile 

Table A.2.1 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

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

21-Day Oral 

Toxicity in 

(Crl:CD®(SD)IGS 

BR rats)

45570601 (2001)

Acceptable/non-guideline 

(21-day study; gavage)

0, 8, 12, 20, or 50 

mg/kg/day 

Repeat exposure: 

Brain ChEI NOAEL = 12 mg/kg/day

Brain ChEI LOAEL = 20 mg/kg/day, based on brain cholinesterase activity 

inhibition in females (day 21).

RBC ChEI NOAEL = 8 mg/kg/day

RBC ChEI LOAEL = 12 mg/kg/day, based on RBC cholinesterase activity 

inhibition in males and females

Single dose exposure: 

RBC ChEI NOAEL = 20 mg/kg.

RBC ChEI LOAEL = 50 mg/kg, based on RBC cholinesterase activity in 

both sexes.

Brain ChEI NOAEL =12 mg/kg.

Brain ChEI LOAEL = 20 mg/kg, based on brain cholinesterase activity 

inhibition (ChEI) in males (22%). At 50 mg/kg, males had 54% and 

females had 23% brain cholinesterase inhibition.

BMDL10 = 6.7 mg/kg/day

BMD10 = 9.9 mg/kg/day, based on female RBC ChE inhibition

BMDL10 = 12.2 mg/kg/day

BMD10 = 14.7 mg/kg/day, based on female brain ChE inhibition
Page 70 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3150

90-Day Oral 

Toxicity (Sprague 

Dawley rats)

43371201 (1990)

Acceptable/guideline

0, 100, 2000, or 5000 ppm 

(diet)

Males: 0, 6.7, 142, and 375 

mg/kg/day;

Females: 0, 10.0, 197, and 

467 mg/kg/day.

BMDL10 = 8.0 mg/kg/day

BMD10 = 10.49 mg/kg/day, 

based on female RBC ChE 

inhibition

RBC ChEI NOAEL = 6.7 mg/kg/day

RBC ChEI LOAEL = 142 mg/kg/day, based on RBC ChEI in both sexes, 

reduced body weights (both sexes), bilateral basophilic tubules of the 

kidneys in males, increased fat deposition in the adrenal cortex of females, 

centrilobular hepatocellular hypertrophy in females and mid-dose males, 

higher adjusted liver weights (both sexes), higher adjusted adrenal weights 

in females, and thyroid follicular cell hypertrophy in both sexes. At 467 

mg/kg/day, females had a 24% brain cholinesterase activity inhibition, 

although statistical significance was not attained.

BMDL10 = 8.0 mg/kg/day

BMD10 = 10.49 mg/kg/day, based on female RBC ChE inhibition

BMDL10 = 26.3 mg/kg/day

BMD10 = 61.6 mg/kg/day, based on male RBC ChE inhibition

No dose-response for brain ChE inhibition (BMD not run)

870.3200

21/Day Dermal 

Toxicity (Crl:CD 

BR rat)

41342001 (1989)

Acceptable/guideline

0, 10, 100, or 1000 

mg/kg/day

6 hours/day, 5 days/week for 

15 treatments over a 21-day 

period

NOAEL = 100 mg/kg/day

LOAEL = 1000/kg/day, based on plasma cholinesterase inhibition in both 

sexes.

Brain and RBC cholinesterase inhibition were not observed in either sex.

870.3465

28-Day Inhalation 

Toxicity

(Sprague-Dawley 

rat)

48803501 (2012)

Acceptable/guideline

nose-only aerosol 

6 hours/day, 5 days/week for 

3 weeks at exposure 

concentrations of 0, 0.05, 

0.5, or 1.0 mg/L; during the 

final week of exposure 

(week 4), the animals were 

exposed for 7 days

NOAEL= 0.05 mg/L/day

LOAEL = 0.5 mg/L/day, based on an increase in RBC cholinesterase 

inhibition in both sexes. Brain cholinesterase activity was not monitored.

Systemic NOAEL not identified. 

Systemic LOAEL = 0.05 mg/L, based on diffuse adrenal cortical cell 

vacuolation in both sexes, enlarged adrenals in females, and increased 

adrenal weights in females. At 0.5 mg/L and 1.0 mg/L, in addition to the 

adrenal findings, there was a dose-related increase in vacuolation of the 

ovaries in females, an increase in squamous metaplasia of the larynx in 

both sexes, and an increase in follicular cell hyperplasia of the thyroids in 

both sexes.

Sex/Age Compartment BMD10 BMDL10

Female RBC 0.394 0.050

Male RBC 0.122 0.022

 
Page 71 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3700a

Prenatal 

developmental in 

(Sprague Dawley 

Crl:COBS®CD® 

(SD)BR)

TXR# 008124, 

008616, 018781

40152701 (1987)

41828001(1991)

41967201 (1991)

42520101 (1992)

Acceptable/guideline

0 (aqueous 0.5% methyl 

cellulose), 75, 150, or 300 

mg/kg/day 

GD 6-15; 10 mL/kg 

(gavage)

Maternal NOAEL = 75 mg/kg/day

Maternal LOAEL = 150 mg/kg/day, based on a reduction in BWG/FC

At 300 mg/kg/day, there were clinical signs of toxicity (tremors and 

chromodacryorrhea) 

Developmental NOAEL =300 mg/kg/day

Developmental LOAEL = not identified.

NOTE: Cholinesterase activity was not assessed (RBC, brain).

870.3700b

Prenatal 

developmental in 

(New Zealand 

white rabbit)

00127831 (1982)

Acceptable/guideline

0, 150, 375, or 750 

mg/kg/day (1% CMC)

GD 6-19; 5 mL/kg (gavage)

Maternal NOEL = 375 mg/kg/day

Maternal LOEL = 750 mg/kg/day, based on mortality, abortions, and red 

vaginal fluid.

Developmental NOAEL = 375 mg/kg/day

Developmental LOAEL = 750 mg/kg/day, based on an increase in early 

resorptions and corresponding increase in post implantation loss, and a 

decrease in live fetuses/doe.

NOTE: Cholinesterase activity was not assessed (RBC, brain).

870.3800

Reproduction and 

Fertility Effects 

(Charles River CD 

Crl®SD) BR rats)

42054301 (1991)

acceptable/guideline

0, 100, 500, or 2000 ppm 

(diet)

F0 Males 0, 5.2, 26, 102 

mg/kg/day

F1 Males 0, 6.7, 34, 130 

mg/kg/day

F0 Females 0, 7.3, 40, or 

155 mg/kg/day

F1 Females 0, 8.3, 43, or 

168 mg/kg/day

Parental NOAEL = 500 ppm (males 26/females 40 mg/kg/day)

Parental LOAEL = 2000 ppm (males 102/females 155 mg/kg/day), based 

on decreased body weight gain in F1 generation, increased adrenal weights 

of F0 females, and decreased body weight gains in F0 males. 

Offspring NOAEL = 2000 ppm (males 102/females 155 mg/kg/day)

Offspring LOAEL was not identified.

Reproductive NOAEL = 2000 ppm (males 102/females 155 mg/kg/day)

Reproductive LOAEL was not identified. 

NOTE: Cholinesterase activity was not assessed (RBC, brain).
Page 72 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.4100a

Chronic Toxicity

(Sprague-Dawley 

rat)

42980901 (1993)

43335101 (1994)

Acceptable/guideline

0, 100, 1000, or 2000 ppm 

(diet)

Males 0, 4.23, 43.2, or 88.5 

mg/kg/day

Females 0, 5.93, 62.7, or 

125.3 mg/kg/day

(2-year study)

NOAEL = 100 ppm (4.23/5.93 mg/kg/day)

LOAEL = 1000 ppm (43.2/62.7 mg/kg/day), based on histological liver 

(hypertrophy of periacinar hepatocytes in both sexes and centriacinar 

degenerative change in males) and adrenal changes (increased incidence of 

diffuse lipidosis of adrenal zona fasciculata in both sexes); reduced body 

weight; RBC cholinesterase inhibition in females.

RBC cholinesterase inhibition was observed in females at 1000 ppm 

(29%*) and 2000 ppm (36%**) at week 77/78; 18% and 22% at week 

103/104 (not **); brain ChEI in females at 52 and 104 weeks was 17% and 

16% (not **).

NOAEL = 100 ppm (4.23/5.93 mg/kg/day)

LOAEL = 1000 ppm (43.2/62.7 mg/kg/day), based on RBC cholinesterase 

inhibition in females

BMD not run due to lack of dose-response

870.4100b

Chronic toxicity 

(Beagle dog)

42679401 (1993)

Acceptable/guideline

0, 0, 6.25, 500, 1000 

mg/kg/day; (capsule)

4/sex/group

Cholinesterase pre-test, 12, 

26, 52 weeks (plasma, RBC)

Brain at termination (1 year)

NOAEL = 6.25 mg/kg/day

LOAEL = 500 mg/kg/day, based on plasma cholinesterase inhibition (both 

sexes), decreased red blood cell counts, hemoglobin, hematocrit, MCHC, 

MCV, alkaline phosphatase, urine specific gravity, and decreased liver and 

kidney weights.

At 1000 mg/kg/day, increased white blood cell counts (females), increased 

prostate weight, decreased cholesterol (males).

RBC and brain cholinesterase inhibition were not observed at any dose 

level in either sexes.

870.4200a

Combined Chronic 

Toxicity/Carcinoge

nicity

(Sprague Dawley 

rat)

42980901 (1993)

43335101 (1994)

acceptable/guideline

0, 100, 1000, or 2000 ppm 

(diet)

Males 0, 4.23, 43.2, or 88.5 

mg/kg/day

Females 0, 5.93, 62.7, or 

125.3 mg/kg/day

NOAEL = 100 ppm (4.23/5.93 mg/kg/day)

LOAEL = 1000 ppm (43.2/62.7 mg/kg/day), based on histological liver 

(hypertrophy of periacinar hepatocytes in both sexes and centriacinar 

degenerative change in males) and adrenal changes (increased incidence of 

diffuse lipidosis of adrenal zona fasciculata in both sexes); reduced body 

weight; RBC cholinesterase inhibition in females.

RBC cholinesterase inhibition was observed in females at 1000 ppm 

(29%*) and 2000 ppm (36%**) at week 77/78; 18% and 22% at week 

103/104 (not **); brain ChEI in females at 52 and 104 weeks was 17% and 

16% (not **).

NOAEL = 100 ppm (4.23/5.93 mg/kg/day)

LOAEL = 1000 ppm (43.2/62.7 mg/kg/day), based on RBC cholinesterase 

inhibition in females

Increased incidence of thyroid C-cell adenomas in male rats at HDT and 

adrenal pheochromocytomas in males 
Page 73 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.4200b

Carcinogenicity 

(B6C3F1 mouse)

00117443 (1978)

Acceptable/guideline

0, 17.5, 64, 320, 1600, 8000, 

16000 ppm 

0, 2.6, 9.6, 48, 240, 1200, or 

2400 mg/kg/day

NOAEL = 1600 ppm (240 mg/kg/day)

LOAEL = 8000 ppm (1200 mg/kg/day), based on decreased body weight 

gain

Statistically significant increases in combined hepatocellular 

adenoma/carcinoma (primarily carcinomas) in female B6C3F1 mice at 

1600 ppm. 

Other doses considered excessive; combined adenomas/carcinomas in 

males, renal adenomas/carcinomas and combined in males at 16000 ppm

870.4300

Combined Chronic 

Toxicity/Carcinoge

nicity

(Sprague Dawley 

rat)

42980901 (1993)

43335101 (1994)

acceptable/guideline

0, 100, 1000, or 2000 ppm 

Males 0, 4.23, 43.2, or 88.5 

mg/kg/day

Females 0, 5.93, 62.7, or 

125.3 mg/kg/day

See above 

Gene Mutation

870.5100

Salmonella/Escheri

chia

bacterial reverse 

mutation assay

41222508 (1989)

66.7, 100, 333, 667, 1000, or 

3300 μg/plate in the 

presence of or 10, 33.3, 

66.7, 100, 333, or 667 

μg/plate absence of 

mammalian metabolic 

activation (S9-mix)

Strains TA98, TA100, TA1535, TA1537, and TA 1538 of S. typhimurium

were exposed to TCVP from concentrations of 66.7 to 3300 μg/plate in the 

presence and 10-667 μg/plate absence of mammalian metabolic activation 

(S9-mix). There was no evidence of induced mutant colonies over 

background.

Acceptable/Guideline

In vitro mammalian 

cytogenetics

870.5375

Chinese hamster 

ovary cells

41312901 (1989)

Concentrations of 22.9, 

44.9, 59.9, 79.8, or 99.8 

μg/mL without S9; 12.5, 25, 

37,6, or 75.1 μg/mL in the 

presence of S9-mix.

Positive for inducing chromosomal aberrations at 59.9, 79.8 and 99.8 

μg/mL in absence of metabolic activation, but negative at 29.9 or 44.9 

μg/mL in absence of metabolic activation.

Negative for inducing chromosomal aberrations at 12.5, 25, 37.6, or 75.1 

μg/mL in the presence of rat S9 metabolic activation.

Acceptable/Guideline

Unscheduled DNA 

Synthesis 

870.5550 in 

mammalian cells in 

culture

42156401 (1992)

Doses of 5, 7.5, 10, 15, 20, 

23, 25, 27, 30, 35, or 40 

μg/mL of TCVP. 

Concentrations of 35 and 40 μg/mL were lethal. Results were negative. 

Acceptable/Guideline

870.6100

Acute and 28-Day 

Delayed 

Neurotoxicity

(Domestic hen)

41905901 (1990)

Acceptable/guideline

2500 mg/kg x 2 (21 days 

apart)

Negative
Page 74 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.6200a

Acute 

Neurotoxicity 

Screening Battery

(Sprague-Dawley 

Crl:CD®BR rats)

42912501 (1993)

Acceptable/guideline

0, 65, 325, or 650 mg/kg

(gavage)

NOAEL = 65 mg/kg

LOAEL = 325 mg/kg, based on transient neurotoxic effects in both sexes 

consistent with cholinesterase inhibition. No neuropathological effects.

Cholinesterase activity was not monitored in the study.

870.6200b

Subchronic 

Neurotoxicity 

Screening Battery

(Crl:CD® BR rats)

43294101 (1994)

Acceptable/guideline

0, 200, 1000, or 5000 ppm 

(diet)

(0, 100, 500, or 250 

mg/kg/day; standard 

conversion)

NOAEL = 5000 ppm (250 mg/kg/day); HDT

LOAEL = not identified.

Cholinesterase activity was not monitored in the study.

870.6300

Developmental 

Neurotoxicity

(Crl: CD® 

(SD)IGS BR 

VAF/Plus® rats)

46660601 (2005)

acceptable/guideline

0, 10, 50, or 200 mg/kg/day

GD 6 –LD 6 (gavage)

Maternal NOAEL = 200 mg/kg/day

LOAEL = not identified.

Offspring NOAEL = 50 mg/kg/day

LOAEL = 200 mg/kg/day, based on deceased body weight, body weight 

gain, several morphometric linear brain measurements in both sexes, and 

decreased absolute brain weight in males on PND 70

Cholinesterase activity was not monitored in the study.

870.7485

Metabolism and 

Pharmacokinetics

(Sprague-Dawley 

CD rat)

MRID 41988401 (1991)

Acceptable/guideline

5 mg/kg [single and repeat 

(14 days)] and 250 mg/kg 

(single)

Most of radioactivity recovered in urine (46%-60%) and feces (38%-56%) 

within 48 hours post dose; major metabolite in urine was trichloromandelic 

acid (18%-26%); major metabolite in feces was trichlorophenylethanol 

(>13%) .

Since the oral LD50 for female rats is lower the male LD50, it is 

noteworthy that males of all groups excreted more total label as 

trichloromandelic acid, a more completely metabolized form of TCVP; 

high-dose females tended to excrete more of the label as desmethyl TCVP 

(with the phosphate group still attached to the remainder of the molecule), 

a compound that could be derived from TCVP with only a single metabolic 

step. 

870.7600

Dermal Penetration

(Sprague Dawley 

CD rats)

MRID 42111501 (1991)

Acceptable/Guideline

0, 0.01, 0.1, 1, or 5 mg/cm2 

for exposures of 0.5, 1, 2, 4, 

and 10 hours and 10 hour 

wash with 72 hour exposure

Absorbed dose following 0.01 mg/cm2 dose is 9.57% following 10-hour 

exposure.

870.7800

Immunotoxicity

(Crl:CD-1(ICR) 

female mouse)

48794701 (2012)

acceptable/guideline

0, 75, 300, 1200 mg/kg/day

Systemic NOAEL = 1200 mg/kg/day, 

Systemic LOAEL = not identified.

Immunotoxicity NOAEL = 1200 mg/kg/day.

Immunotoxicity LOAEL = not identified.
Page 75 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

Special study

Comparative 

cholinesterase

gestational CCA

(Crl:CD(SD)IGS 

BR VAF/Plus rats)

MRID 48291101 (2010)

Acceptable/non-guideline

1% aqueous (w/v) 

methylcellulose

0, 75, 150, 300 mg/kg/day 

GD 6-21 (gavage)

The main purpose of this study was to determine whether there is 

differential sensitivity between dams and fetuses with respect to 

cholinesterase inhibition following oral exposure to TCVP. 

RBC ChE: Neither the dams nor the fetuses demonstrated RBC ChE

inhibition at dose levels where RBC ChE inhibition (ChEI) would be 

expected. The repeat dosing study (2012, 48773401) conducted in the same 

laboratory in the same strain of rat clearly demonstrated RBC ChE 

inhibition at 50 and 200 mg/kg/day in female rats. In the gestational/fetal 

study, RBC results in the dams were ↓5.1%, ↓15%, and ↓3% RBC ChEI, 

with increasing dose. The fetal RBC data were of little value because only 

one or two fetal samples were available for the control, low, and high dose 

groups and no sample was available for the mid dose group. There was no 

way to compare adult and fetal RBC ChE.activity 

Brain ChE. Brain ChE inhibition was dose dependent in dams (↓31%, 

↓44% and ↓67% with increasing dose). Fetal brain ChE values (↓20%, 

↓20.9% and ↓20.8%, with increasing dose) showed no dose-response and 

are questionable. However, the data suggest that the fetal brain ChE is not 

more sensitive to inhibition by TCVP than the dams. 

Plasma ChE. Plasma ChE inhibition in dams was dose dependent ↓62%, 

↓71% and ↓77%, with increasing dose). Fetal plasma ChE values were 

↓22%, ↓18.5% and ↓20.8%, with increasing dose. The lack of a dose 

response raises questions as to whether these lower values are actually 

inhibition. However, the data do not indicate that the fetuses are more 

sensitive than the dams. 

Classification: This in vivo comparative ChE study is classified as 

Acceptable/non-guideline. The inability of the laboratory to detect RBC 

ChE in the dams and the flat dose response curves for the brain ChE in 

both pups and adults confounds the interpretation of the study. However, 

no additional gestational CCA study is being requested at this time because 

there is no indication that the fetuses were more sensitive than the dams. 
Page 76 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

Special studies

Comparative 

cholinesterase

Acute CCA

(Crl:CD(SD)IGS 

BR VAF/Plus 

strain rat)

MRID 48294601 (2010)

Acceptable/non-guideline

Single gavage dose (1% 

aqueous methylcellulose)

young adult, PND 11, PND 

21

0, 75, 150 or 300 mg/kg

The main purpose of this study was to determine whether there is 

differential sensitivity among the PND11, PND21 and adults with respect 

to cholinesterase inhibition following exposure to TCVP. 

Overall, there is little confidence in the ChE data mainly because of the 

lack of clear dose and temporal responses. The number of samples in 

many cases was inadequate due to sample loss (no sample available, 1, 2, 

or 3 samples). Also, duplicate samples that did not replicate contributed to 

the low number of samples available for a meaningful assessment. Brain 

ChE assessment also appeared to be affected by the low number of 

samples. The results for all three enzyme sources indicated that there was 

inhibition at all doses but there was poor dose response with the degree of 

apparent inhibition at the higher doses often less that at the low dose of 75 

mg/kg/day. There was also a lack of temporal concordance with high 

apparent inhibition at one time, a much lower degree at the following time 

point, and back to the higher level at the next time point. Further, there was 

more or similar apparent inhibition at the low dose of 75mg/kg in this acute 

study than there was in the repeat dosing study (2012, MRID 48773401, 

eleven daily doses) at 200 mg/kg/day and in the gestational study (2010, 

MRID 48291101, fifteen daily doses). It is noted that the repeat dosing 

study clearly indicated that there was no increase in sensitivity of the pups 

relative to the adults with regard to ChEI by TCVP. However, in this acute 

study, there were several comparisons among the PND11, PND21 and 

adults that suggested the pups were more sensitive. Although there is little 

confidence in the ChEI data in this study, no additional acute CCA study is 

being requested at this time. 

Benchmark Dose (BMD) modeling. BMD modeling was performed but 

could not be done with the RBC data or for the PND11 brain data because 

of too few samples and/or the data would not otherwise fit the models. 

BMD modeling for the brain ChE data (3- hour time point) indicated that 

for males, the adults were slightly more sensitive than the PND 21 pups but 

the females were considered similar with respect to the BMD10 and 

BMDL10. 

This study is classified as Acceptable/Non-Guideline. There is too much 

variability in the ChE data to make meaningful comparisons for sensitivity 

for RBC and brain ChE inhibition. Although there is little confidence in 

the ChEI data in this study, no additional acute CCA study is being 

requested at this time. 
Page 77 of 152

Special studies

Comparative 

cholinesterase

repeat CCA

(Crl:CD(SD)IGS 

BR VAF/Plus 

strain rat)

48773401 (2012)

Acceptable/Non-guideline. 

0, 5, 10, 50 or 200 

mg/kg/day for both ages.

The main purpose of this study was to determine whether there is 

differential sensitivity between young adults and PND 11 pups with respect 

to cholinesterase inhibition following repeat oral exposure (11 doses) to 

TCVP. 

Table 1 shows the adult ChEI data (3 hours after last dose) and Table 2 

shows the pup ChEI data. There was a dose-related reduction in RBC and 

brain cholinesterase activity in both sexes and both age groups

Table 1. Inhibition (%) of RBC and Brain ChE Activity in Adult Rats 

(repeat)

Dose (mg/kg/day) Males Females

RBC

5 12% 8%

10 13%* 8.7%

50 30%** 40%**

200 36%** 62%**

Brain

5 2% -

10 7% 12%*

50 14.9%** 42%**

200 17.8%** 57%**

Table 2. Inhibition (%) of RBC and Brain ChE Activity in Pups (repeat)

Dose (mg/kg/day) Males Females

RBC

5 2% -

10 2% -

50 33%** 19%**

200 60%** 62%

Brain

5 4% 4%

10 6% 6%

50 16%** 18.7%**

200 46%** 45%**

RBC ChE inhibition. At 50 mg/kg/day, both male pups and male adults 

had similar levels of inhibition (30% to 33%), whereas at 200 mg/kg/day, 

the male pups were inhibited to ≈60% compared to 36% in the male adult 

rats. At 50 mg/kg/day, adult females demonstrated more inhibition (≈40%) 

than the female pups (19%) but at 200 mg/kg/day, both female pups and 

female adults had ~62% inhibition. 

Brain ChE inhibition. Adult females displayed greater brain ChE inhibition 

at all dose levels than the adult males, whereas a similar magnitude of 

brain ChE inhibition was observed in male and female pups. Adult females 

displayed brain ChE inhibition at all dose levels. 
Page 78 of 152

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Tetrachlorvinphos (TCVP)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

A benchmark dose analysis of the cholinesterase data (RBC and brain) was 

performed that provides both the BMD10 and BMDL10 of adults and PND11 

pups. 

BMD10s and BMDL10s for Adult Rat and PND 11 Pup Cholinesterase

RBC BMD10 RBC BMDL10 Brain BMD10 Brain BMDL10

Adult ♂ 7.7178 3.5942 33.803 24.4489

Adult ♀ 8.6762 6.1335 7.1764 5.4980

PND 11 ♂ 20.4688 15.9719 33.4825 26.5707

PND 11 ♂ 20.5608 13.1692 24.2224 18.9412

Overall conclusion. The main objective of this study was to attempt to 

determine if the pups are more sensitive than the adults to the inhibitory 

potential of TCVP. Based on assignment of the NOAEL and LOAEL and 

the BMD modeling, there was no demonstration for increased sensitivity of 

the pups relative to the adults for either RBC or brain ChE. It is noted, 

however, that the magnitude of the high dose male pup brain and RBC 

ChE inhibition is greater than that in the adult males, but the significance is 

not established. 

Classification: The classification of this repeat dosing in vivo comparative 

cholinesterase inhibition study is Acceptable/Non-Guideline. The study 

does not satisfy a guideline requirement. It satisfies a data call-inrequirement for TCVP for an 11-day repeat dosing comparative ChE study 

in adult rats versus postnatal day 11-21 pups. 

Table A.3.1 TCVP - RBC and Brain Cholinesterase Inhibition NOAELs and LOAELs- % AChEI at LOAEL

Study Compartment NOAEL (mkd) LOAEL (mkd) % ChEI

ORAL

MRID 48294601

Acute CCA

(PND 11)

RBC

Brain

-

-

75A ♀24-28%B; ♂42-64%C

♀22-38%; ♂19-40%

MRID 48294601

Acute CCA

(PND 21)

RBC

Brain

-

-

75A ♀27-36%; ♂19-49%

♀25-54%; ♂24-45%

MRID 48294601

Acute CCA

(young adult)

RBC

Brain

-

-

75A ♀22%; ♂26-35%

♀40%; ♂28-56%

MRID 

Single dose

RBC

Brain

20

12

50

20

♀37%; ♂46%

♀10%; ♂22%

MRID 48773401

Repeat CCA

(adult male 

11 doses) 

RBC

Brain

5

10

10

50

13%D

15%

MRID 48773401

Repeat CCA

RBC

Brain

10

5

50

10

40%

12%
Page 79 of 152

Table A.3.1 TCVP - RBC and Brain Cholinesterase Inhibition NOAELs and LOAELs- % AChEI at LOAEL

Study Compartment NOAEL (mkd) LOAEL (mkd) % ChEI

(adult female 

11 doses)

MRID 48773401

Repeat CCA

(male pup)

RBC

Brain

10

10

50

50

33%

16%

MRID 48773401

Repeat CCA

(female pup)

RBC

Brain

10

10

50

50

19%

19%

MRID 48291101

Gestational CCA

(dams 16 doses)

RBC

Brain

- 75A -

31%

MRID 48291101

Gestational CCA

(fetuses)

RBC

Brain

- 75A -

10%

MRID 45570601

21-day

RBC

Brain

12

8

20

12

♀14-35%; ♂19-30%

♀16%

MRID 43371201

90-day

RBC

Brain

6

142

142

467

♀80%; ♂30%

♀24%

MRID 42980901

MRID 43335101

Chronic 365 days

RBC

Brain

5.9 63 ♀29%

♀17%

INHALATION – DERMAL

MRID 48803501

28-day inhalation

RBC 0.05 mg/L 0.5 mg/L ♀35%♂24%

MRID 41342001

21-day dermal

RBC

Brain

-

-

-

-

No inhibition at 1000 

mg/kg/day

ALowest dose tested; Bpre-test was 27%; Cpre-test was 34%; D30% at 50 mkd; 36% at 200 mkd; 
Page 80 of 152

Appendix B. Results for BMD/BMDL modeling for TCVP 

Benchmark dose (BMD) analyses were performed with EPA’s Benchmark Dose Software 

(Version 2.4) using an exponential model for continuous data14. 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 

AChE-inhibiting pesticides. Model runs for AChE 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 B. 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 AChE 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 B.1. Results of BMD Exponential Modeling for Brain and RBC AChE 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

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

 

14 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 81 of 152

Table B.1. Results of BMD Exponential Modeling for Brain and RBC AChE 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 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 0.022 mg/L

Adult Female RBC 0.394 mg/L 0.050 mg/L
Page 82 of 152

Appendix C. Physical/Chemical Properties for Tetrachlorvinphos

Table C.1 Physicochemical Properties of the Technical Grade Test Compound: Tetrachlorvinphos

Parameter Value Reference 1

Melting point/range 94.5 oC (MRID 41222503)

pH 5.5; 1% solution (MRID 41222503)

Density 0.83 g/mL (MRID 41222503)

Water solubility (25°C) 0.00116 g/100g (MRID 41222503)

Solvent solubility (mg/100mg at 25°C)

chloroform 80

methanol 21

acetone 44

hexane 0.8

toluene 28

(MRID 41222503)

Vapor pressure (25°C) 2.6 x 10-7 mm Hg (MRID 41222503)

Dissociation constant, pKa non-ionizable (MRID 41222503)

Octanol/water partition coefficient, Log(KOW) 3350 average KOW at 25 oC (MRID 41222503)

UV/visible absorption spectrum Not available

1 Cited reference was reviewed under CB No. 7468, 4/3/91, R. Perfetti.
Page 83 of 152

Appendix D. TCVP and Metabolites

Chemical Name Structure Physical/Chemical Properties1

Tetrachlorvinphos

IUPAC: (Z)-2-chloro-1-(2,4,5-

trichlorophenyl)vinyl dimethyl phosphate

CAS: (1Z)-2-chloro-1-(2,4,5-

trichlorophenyl)ethenyl dimethyl phosphate

CAS Reg. No. 22248-79-9

COP(=O)(OC)OC(=CCl)c1cc(Cl)c(

Cl)cc1Cl

O

O

P O

O

Cl

Cl

Cl Cl

Molecular weight: 365.96 g/mol

VP: 2.6E-07 torr

Solubility: 11.6 mg/L

Log Kow: 3.53

Koc: 520-1100 L/kgoc

Des-O-methyl tetrachlorvinphos

IUPAC: (Z)-2-chloro-1-(2,4,5-

trichlorophenyl)vinyl methyl phosphate

CAS: (1Z)-2-chloro-1-(2,4,5-

trichlorophenyl)ethenyl methyl phosphate

COP(=O)(O)OC(=CCl)c1cc(Cl)c(Cl

)cc1Cl

O

O

P O

OH

Cl

Cl

Cl Cl

Molecular weight: 351.94 g/mol

VP: 4.27E-08 torr

Solubility: 3.768 mg/L

Log Kow: 3.75

Koc: 702-827 L/kgoc

1-(2,4,5-trichlorophenyl)ethanediol

C(O)(CO)c1cc(Cl)c(Cl)cc1Cl

OH

Cl

Cl Cl

OH

Molecular weight: 241.5 g/mol

VP: 4.37E-06 torr

Solubility: 250 mg/L

Log Kow: 2.37

Koc: 29-36 L/kgoc

TCPEol (SD 15509, AA849)

1-(2,4,5-trichlorophenyl)ethanol

1-(2,4,5-trichlorophenyl)ethan-1-ol

CC(O)c1cc(Cl)c(Cl)cc1Cl

OH

Cl

Cl Cl

Molecular weight: 225.5 g/mol

VP: 2.37E-04 torr

Solubility: 123 mg/L

Log Kow: 3.43

Koc: 319-359 L/kgoc

TCPEone (CO300)

2,4,5-trichloroacetophenone

CC(=O)c1cc(Cl)c(Cl)cc1Cl

O

Cl

Cl Cl

Molecular weight: 223.5 g/mol

VP: 6.32E-03 torr

Solubility: 27.4 mg/L

Log Kow: 3.61

Koc: 492-1,828 L/kgoc
Page 84 of 152

Chemical Name Structure Physical/Chemical Properties1

TCCEol (SD15125, AA576)

l-(2,4,5-trichlorophenyl)-2-chloroethanol

C(Cl)C(O)c1cc(Cl)c(Cl)cc1Cl

Molecular weight: 260 g/mol

VP: 2.11E-05 torr

Solubility: 250 mg/L

Log Kow: 3.68

Koc: 494-608 L/kgoc

TCBA (SD 15917)

2,4,5-Trichlorobenzoic acid

C(=O)(O)c1cc(Cl)c(Cl)cc1Cl

Molecular weight: 225.5 g/mol

VP: 5.52E-04 torr

Solubility: 35.3 mg/L

Log Kow: 3.47

Koc: 157-166 L/kgoc

1. Physical and chemical properties for degradates obtained through EPISuite 4.11.
Page 85 of 152

Appendix E. International MRLs and U.S. Tolerances

Table E.1. Tetrachlorvinphos: Summary of U.S. and International Tolerances and Maximum Residue 

Limits.

Commodity

U.S. Tolerances, 40 CFR §180.252 1

Codex MRL Canada’s MRL 2

Established U.S. 

Tolerance, ppm

Reassessed U.S. 

Tolerance, ppm 

Milk, fat 

(reflecting 

negligible 

residues in 

whole milk)

0.5 (of which not 

more than 0.05 ppm 

is tetrachlorvinphos 

per se) 

milk: 0.1 (of which not 

more than 0.04 ppm is 

tetrachlorvinphos per se)

None None

Cattle and Hog, 

Fat

Fat of cattle and 

hog: 0.2 (of which 

not more than 0.1 

ppm is 

tetrachlorvinphos 

per se)

Fat of cattle and hog: 1.0 

(of which not more than 

0.8 ppm is 

tetrachlorvinphos per se)

None 1.5 3

Cattle and Hog, 

Muscle

meat of cattle and 

hog: 2.0 (of which 

not more than 2.0 

ppm is 

tetrachlorvinphos 

per se)

meat of cattle and hog: 

0.3 (of which not more 

than 0.2 ppm is 

tetrachlorvinphos per se)

None 1.5 3

Cattle and Hog, 

Kidney

kidney of cattle and 

hog: 1.0 (of which 

no more than 0.05 

ppm is 

tetrachlorvinphos 

per se)

meat byproducts of cattle 

and hog : 1.0 (of which 

no more than 0.6 ppm is 

tetrachlorvinphos per se) 

None 1.5 3

Cattle and Hog, 

Liver

liver of cattle and 

hog: 0.5 (of which 

no more than 0.05 

ppm is 

tetrachlorvinphos 

per se)

None 1.5 3
Page 86 of 152

Table E.1. Tetrachlorvinphos: Summary of U.S. and International Tolerances and Maximum Residue 

Limits.

Commodity

U.S. Tolerances, 40 CFR §180.252 1

Codex MRL Canada’s MRL 2

Established U.S. 

Tolerance, ppm

Reassessed U.S. 

Tolerance, ppm 

Cattle and Hog, 

Meat byproducts

meat byproducts, 

except kidney and 

liver of cattle and 

hog: 1.0

None 1.5 3

Eggs 0.2 (of which not 

more than 0.05 ppm 

is tetrachlorvinphos 

per se)

0.3 (of which not more 

than 0.03 ppm is 

tetrachlorvinphos per se)

None None

Poultry, muscle meat of poultry: 

3.0 (of which not 

more than 3.0 ppm 

is tetrachlorvinphos 

per se)

meat of poultry: 0.4 (of 

which not more than 0.1 

ppm is tetrachlorvinphos 

per se)

None 0.75 4

Poultry, liver 2.0 (of which not 

more than 0.05 ppm 

is tetrachlorvinphos 

per se)

meat byproducts of 

poultry: 20 (of which not 

more than 6.0 ppm is 

tetrachlorvinphos per se)

None 0.75 4

Poultry, meat 

byproducts

meat byproducts, 

except liver, of 

poultry: 2.0

meat byproducts of 

poultry: 20 (of which not 

more than 6.0 ppm is 

tetrachlorvinphos per se)

1.4 (of which not more 

than 0.1 ppm is 

tetrachlorvinphos per se)

None 0.75 4

Poultry, fat 7.0 (of which not 

more than 7.0 ppm 

is tetrachlorvinphos 

per se)

None 0.75 4

Apples None None None 10

Grapes None None None 10

1

 Current US residue definition is tetrachlorvinphos, des-O-methyl tetrachlorvinphos, 1-(2,4,5-

trichlorophenyl)ethanol (free and conjugated forms), 2,4,5-trichloroacetophenone, and 1-(2,4,5-

trichlorophenyl)ethanediol. Des-O-methyl tetrachlorvinphos should be added to the definition. 

2 Canada residue definition is 2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl phosphate (TCVP) and its low 

melting isomer.
Page 87 of 152

3

 Meat, meat byproducts and fat of cattle and hogs, calculated on the fat content.

4

 Meat, meat byproducts and fat of poultry, calculated on the fat content.
Page 88 of 152

Appendix F. Summary of Residential Handler Non-Cancer Exposures and Risks
Page 89 of 152

Table F.1. Residential Handler Non-cancer (Steady State) Exposure and Risk Estimates from Use of TCVP Pet Collar Products. No dermal 

hazard.

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

Dose 

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

Use of Spot-On Exposure Data - 2012 Residential SOPs

Application of TCVP 

Collars

2596-49:

Cat

NA 120 Negligible

0.0036:

11 gram collar

2 

animals 

treated per 

day

0.0012

NA, No 

Dermal 

Hazard

Negligible

2596-50, 62:

Dog

0.0061: 

19 gram collar 0.0020

0.010:

32 gram collar 0.0034

2596-63:

Cat

0.0048:

15 gram collar 0.0016

0.0055:

17 gram collar 0.0018

2596-83:

Cat

0.0039:

12 gram collar 0.0013

0.0080:

25 gram collar 0.0027

2596-84:

Dog

0.0061:

19 gram collar 0.0021

0.010:

32 gram collar 0.0034

2596-139:

Cat

0.0032:

10 gram collar 0.0011

2596-139:

Dog

0.016:

50 gram collar 0.0054

11556-164: 0.0072: 0.0024
Page 90 of 152

Dog 24 gram collar

11556-165:

Cat

0.0045: 

15 gram collar 0.0015

Use of TCVP Dust Applicator Exposure Data

Application of TCVP 

Collars

2596-49:

Cat

Inhalation; 

300 1,700 3.1

0.0036:

11 gram collar

2 

animals 

treated per 

day

0.043

N/A, No 

Dermal 

Hazard

0.00033 4,900

2596-50, 62:

Dog

0.0061: 

19 gram collar 0.073 0.00055 2,900

0.010:

32 gram collar 0.12 0.00092 1,700

2596-63:

Cat

0.0048:

15 gram collar 0.057 0.00043 3,700

0.0055:

17 gram collar 0.065 0.00049 3,300

2596-83:

Cat

0.0039:

12 gram collar 0.046 0.00035 4,600

0.0080:

25 gram collar 0.096 0.00072 2,200

2596-84:

Dog

0.0061:

19 gram collar 0.073 0.00055 2,900

0.010:

32 gram collar 0.12 0.00092 1,700

2596-139:

Cat

0.0032:

10 gram collar 0.038 0.00029 5,500

2596-139:

Dog

0.016:

50 gram collar 0.19 0.00144 1,100

11556-164:

Dog

0.0072:

24 gram collar 0.086 0.00065 2,500

11556-165:

Cat

0.0045: 

15 gram collar 0.054 0.00041 3,900
Page 91 of 152

1 Based on registered TCVP pet product labels. 

2 Based on HED’s 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide).

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 (69 kg). Dermal dose presented only for purpose of calculation of cancer risks for residential handlers. 

4 No dermal MOE estimated due to lack of dermal hazard. 

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/pet) × Area Treated or Amount Handled (pets/day) ÷ Body Weight (69 kg).

6 Inhalation MOE = Inhalation NOAEL (1.59 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

Table F.2. Residential Handler Non-cancer (Steady State) Exposure and Risk Estimates from Use of TCVP Dust/Powder and 

Pump/Trigger Spray Products. No dermal hazard.

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

Dose 

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

Application of TCVP 

Dusts/Powders

47000-123:

Dog

Inhalation:

300 1,700 3.1

0.00037:

small

2 

animals 

treated per 

day

0.0018

N/A, No 

Dermal 

Hazard

0.000034 47,000

0.00094:

medium 0.0044 0.000084 19,000

0.0015:

large 0.0071 0.00013 12,000

47000-123: 

Cat

0.000094:

small 0.00044 0.0000084 190,000

0.00023:

medium 0.0011 0.000020 79,000

0.00034:

large 0.0016 0.000030 53,000

2596-78:

Cat

0.00062:

small 0.0029 0.000056 29,000

0.0010:

large 0.0049 0.000093 17,000

2596-79; 

Dog

0.0010: 

small 0.0049 0.000093 17,000

0.0021:

medium 0.0097 0.00019 8,600

0.0026: 

large 0.0122 0.00023 6,900

67517-82:

Dog

0.0011:

small 0.0053 0.00011 16,000
Page 92 of 152

Table F.2. Residential Handler Non-cancer (Steady State) Exposure and Risk Estimates from Use of TCVP Dust/Powder and 

Pump/Trigger Spray Products. No dermal hazard.

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

Dose 

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

0.0028:

medium 0.013 0.00025 6,300

0.0045:

large 0.021 0.00040 3,900

67517-82:

Cat

0.00028:

small 0.0013 0.000025 63,000

0.00067:

medium 0.0032 0.000061 26,000

0.0010:

large 0.0048 0.000091 18,000

Application of TCVP 

Pump/Trigger Sprays

2596-126,

-140:

Cat

(Trigger)

820 3.3

0.00055:

small 0.0013

N/A, No 

Dermal 

Hazard

0.000053 30,000

0.00077:

medium 0.0018 0.000074 22,000

2596-140

Cat

(Pump)

0.00011:

small 0.00026 0.000011 150,000

0.00016:

large 0.00036 0.000015 110,000

2596-125, -

140:

Dog

(Trigger)

0.00077:

small 0.0018 0.000074 22,000

0.00088:

medium 0.0020 0.000084 19,000

0.0015:

large 0.0035 0.00015 11,000

1 Based on registered TCVP pet product labels. 

2 Based on HED’s 2012 Residential SOPs (http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide)

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 (69 kg). Dermal dose presented only for purpose of calculation of cancer risks for residential handlers. 

4 No dermal MOE estimated due to lack of dermal hazard. 

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/pet) × Area Treated or Amount Handled (pets/day) ÷ Body Weight (69 kg).

6 Inhalation MOE = Inhalation NOAEL (1.59 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 93 of 152

Appendix G. Summary of Residential Handler Cancer Exposure and Risk Estimates

Table G.1. Residential Handler Cancer Exposure and Risk Estimates from TCVP Pet Collar 

Products

Reg No./ 

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

Pet Collars - Spot-On Exposure Data (2012 Residential SOPs)

2596-49: Cat Any

Adult

8.5E-06 1.6E-08

2596-50, 62: Dog

Small 1.4E-05 2.6E-08

Medium, Large 2.4E-05 4.4E-08

2596-63: Cat

Small 1.1E-05 2.1E-08

Medium, Large 1.3E-05 2.3E-08

2596-83: Cat

Small 9.0E-06 1.7E-08

Medium, Large 1.9E-05 3.4E-08

2596-84: Dog

Small 1.4E-05 2.6E-08

Medium, Large 2.4E-05 4.4E-08

2596-139: Cat Any 7.5E-06 1.4E-08

2596-139: Dog Any 3.8E-05 6.9E-08

11556-164: Dog Any 1.7E-05 3.1E-08

11556-165: Cat Any 1.1E-05 1.9E-08

Pet Collars - TCVP Dust Applicator Exposure Data 

2596-49: Cat Any

Adult

1.2E-04 2.2E-07

2596-50, 62: Dog

Small 2.1E-04 3.8E-07

Medium, Large 3.5E-04 6.4E-07

2596-63: Cat

Small 1.6E-04 3.0E-07

Medium, Large 1.8E-04 3.4E-07

2596-83: Cat

Small 1.3E-04 2.4E-07

Medium, Large 2.7E-04 5.0E-07

2596-84: Dog

Small 2.1E-04 3.8E-07

Medium, Large 3.5E-04 6.4E-07

2596-139: Cat Any 1.1E-04 2.0E-07

2596-139: Dog Any 5.4E-04 9.9E-07

11556-164: Dog Any 2.4E-04 4.5E-07

11556-165: Cat Any 1.5E-04 2.8E-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 of D426984. 

3 Cancer risk estimates = Total LADD × Q1

*

, where Q1

* = 1.83 x 10-3

(mg/kg/day)-1
Page 94 of 152

Table G.2. Residential Handler Cancer Exposure and Risk Estimates from TCVP Pet 

Products

Reg No./ 

Animal Type

Animal Size Lifestage LADD1,2 Cancer Risk 

Estimate3

Dust/Powder

47000-123: Dog

Small

Adult

1.9E-05 3.5E-08

Medium 4.7E-05 8.7E-08

Large 7.6E-05 1.4E-07

47000-123: Cat

Small 4.7E-06 8.7E-09

Medium 1.1E-05 2.1E-08

Large 1.7E-05 3.1E-08

2596-78: Cat

Small 3.1E-05 5.7E-08

Medium 5.2E-05 9.6E-08

2596-79: Dog

Small 5.2E-05 9.6E-08

Medium 1.0E-04 1.9E-07

Large 1.3E-04 2.4E-07

67517-82: Dog

Small 5.7E-05 1.0E-07

Medium 1.4E-04 2.6E-07

Large 2.3E-04 4.2E-07

67517-82: Cat

Small 1.4E-05 2.6E-08

Medium 3.4E-05 6.2E-08

Large 5.1E-05 9.4E-08

Pump/Trigger Sprays

2596-126:

-140: Cat (Trigger)

Small

Adult

1.4E-05 2.5E-08

Large 1.9E-05 3.5E-08

2596-140: 

Cat (Pump)

Small 2.8E-06 5.1E-09

Large 3.9E-06 7.2E-09

2596-125, -140:

Dog (Trigger)

Small 1.9E-05 3.5E-08

Medium 2.2E-05 4.0E-08

Large 3.9E-05 7.0E-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 of D426984.

3 Cancer risk estimates = Total LADD × Q1

*

, where Q1

* = 1.83 x 10-3

(mg/kg/day)-1
Page 95 of 152

Appendix H. Summary of Residential Post-Application Non-Cancer Exposure and Risk 

Estimates

Table H.1. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Liquid Formulation). Incidental Oral LOC is an MOE 

= 1,000. 

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Amitraz Exposure Data (MRID 49468801)

2596-49: 

Cat

Adult Dermal

1,650

Small 0.0086 X

Medium 0.0051 X

Large 0.0032 X

Children

1 < 2

Dermal Small 0.019 X

Incidental Oral 0.0020 4,100

Dermal Medium 0.011 X

Incidental Oral 0.0012 6,800

Dermal Large 0.0070 X

Incidental Oral 0.00074 11,000

2596-50, 

62:

Dog

Adult Dermal

2,770 Small 0.0072 X

4,670 Large 0.0033 X

Children

1 < 2

Dermal 2,770 Small 0.016 X

Incidental Oral 0.0016 4,900

Dermal 4,670 Large 0.0072 X

Incidental Oral 0.00076 11,000

2596-83: 

Cat

Adult Dermal 1,750 Small 0.0091 X

3,650 Large 0.0071 X

Children

1 < 2

Dermal 1,750 Small 0.020 X

Incidental Oral 0.0021 3,800

Dermal 3,650 Large 0.016 X

Incidental Oral 0.0016 4,900

2596-139: 

Cat

Adult Dermal

1,460

Small 0.0076 X

Medium 0.0045 X

Large 0.0028 X

Children

1 < 2

Dermal Small 0.017 X

Incidental Oral 0.0017 4,600

Dermal Medium 0.010 X

Incidental Oral 0.0010 7,700

Dermal Large 0.0062 X

Incidental Oral 0.00065 12,000

11556-164:

Dog

Adult Dermal

3,290

Small 0.0085 X

Medium 0.0037 X

Large 0.0023 X

Children

1 < 2

Dermal Small 0.020 X

Incidental Oral 0.0019 4,100

Dermal Medium 0.0080 X

Incidental Oral 0.00084 9,600
Page 96 of 152

Table H.1. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Liquid Formulation). Incidental Oral LOC is an MOE 

= 1,000. 

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Dermal Large 0.0051 X

Incidental Oral 0.00053 15,000

11556-165:

Cat

Adult Dermal

2,060

Small 0.011 X

Medium 0.0064 X

Large 0.0040 X

Children

1 < 2

Dermal Small 0.023 X

Incidental Oral 0.0024 3,300

Dermal Medium 0.014 X

Incidental Oral 0.0015 5,500

Dermal Large 0.0088 X

Incidental Oral 0.00092 8,700

2596-84: 

Dog

Adult Dermal 2,770 Small 0.0072 X

4,670 Large 0.0033 X

Children

1 < 2

Dermal 2,770 Small 0.016 X

Incidental Oral 0.0016 4,900

Dermal 4,670 Large 0.0072 X

Incidental Oral 0.00076 11,000

2596-139:

Dog

Adult Dermal

7,300

Small 0.019 X

Medium 0.0081 X

Large 0.0052 X

Children

1 < 2

Dermal Small 0.041 X

Incidental Oral 0.0043 1,800

Dermal Medium 0.018 X

Incidental Oral 0.0019 4,300

Dermal Large 0.011 X

Incidental Oral 0.0012 6,800

2596-63: 

Cat

Adult Dermal

2,190 Small 0.011 X

2,480 Large 0.0048 X

Children

1 < 2

Dermal 2,190 Small 0.025 X

Incidental Oral 0.0026 3,100

Dermal 2,480 Large 0.011 X

Incidental Oral 0.0011 7,200

1 Based on registered TCVP pet products as detailed in Table 4.0 of D426984.

2 Dose (mg/kg/day) equations provided in Appendix A of D426984.

3 MOE = Incidental Oral PoD (8.0 mg/kg/day) ÷ Dose (mg/kg/day).
Page 97 of 152

Table H.2. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Liquid Formulation). Incidental Oral LOC is an MOE 

= 1,000.

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Davis, M., et al (2008)

2596-49: 

Cat

Adult Dermal

1,650

Small 0.024 X

Medium 0.015 X

Large 0.0091 X

Children

1 < 2

Dermal Small 0.053 X

Incidental Oral 0.0056 1,400

Dermal Medium 0.032 X

Incidental Oral 0.0033 2,400

Dermal Large 0.020 X

Incidental Oral 0.0021 3,800

2596-50, 

62:

Dog

Adult Dermal

2,770 Small 0.020 X

4,670 Large 0.0094 X

Children

1 < 2

Dermal 2,770 Small 0.045 X

Incidental Oral 0.0047 1,700

Dermal 4,670 Large 0.021 X

Incidental Oral 0.0021 3,700

2596-83: 

Cat

Adult Dermal 1,750 Small 0.026 X

3,650 Large 0.020 X

Children

1 < 2

Dermal 1,750 Small 0.057 X

Incidental Oral 0.0059 1,400

Dermal 3,650 Large 0.044 X

Incidental Oral 0.0046 1,700

2596-139: 

Cat

Adult Dermal

1,460

Small 0.021 X

Medium 0.013 X

Large 0.0081 X

Children

1 < 2

Dermal Small 0.047 X

Incidental Oral 0.0049 1,600

Dermal Medium 0.028 X

Incidental Oral 0.0030 2,700

Dermal Large 0.018 X

Incidental Oral 0.0018 4,300

11556-164:

Dog

Adult Dermal

3,290

Small 0.024 X

Medium 0.010 X

Large 0.0066 X

Children

1 < 2

Dermal Small 0.053 X

Incidental Oral 0.0055 1,400

Dermal Medium 0.023 X

Incidental Oral 0.0024 3,400

Dermal Large 0.015 X

Incidental Oral 0.0015 5,300

11556-165: Adult Dermal 2,060 Small 0.030 X
Page 98 of 152

Table H.2. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Liquid Formulation). Incidental Oral LOC is an MOE 

= 1,000.

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Cat Medium 0.018 X

Large 0.011 X

Children

1 < 2

Dermal Small 0.066 X

Incidental Oral 0.0069 1,200

Dermal Medium 0.040 X

Incidental Oral 0.0042 1,900

Dermal Large 0.025 X

Incidental Oral 0.0026 3,100

2596-84: 

Dog

Adult Dermal 2,770 Small 0.020 X

4,670 Large 0.0094 X

Children

1 < 2

Dermal 2,770 Small 0.045 X

Incidental Oral 0.0047 1,700

Dermal 4,670 Large 0.021 X

Incidental Oral 0.0021 3,700

2596-139:

Dog

Adult Dermal

7,300

Small 0.054 X

Medium 0.023 X

Large 0.015 X

Children

1 < 2

Dermal Small 0.12 X

Incidental Oral 0.012 650

Dermal Medium 0.050 X

Incidental Oral 0.0053 1,500

Dermal Large 0.032 X

Incidental Oral 0.0034 2,400

2596-63: 

Cat

Adult Dermal

2,190 Small 0.032 X

2,480 Large 0.014 X

Children

1 < 2

Dermal 2,190 Small 0.071 X

Incidental Oral 0.0074 1,100

Dermal 2,480 Large 0.030 X

Incidental Oral 0.0031 2,500

1 Based on registered TCVP pet products as detailed in Table 4.0 of D426984.

2 Dose (mg/kg/day) equations provided in Appendix A of D426984.

3 MOE = Incidental Oral PoD (8.0 mg/kg/day) ÷ Dose (mg/kg/day).
Page 99 of 152

Table H.3. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Solid Formulation). Incidental Oral LOC is an MOE 

= 1,000. 

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Amitraz Exposure Data (MRID 49468801)

2596-49: 

Cat

Adult Dermal

1,650

Small 0.23 X

Medium 0.14 X

Large 0.086 X

Children

1 < 2

Dermal Small 0.51 X

Incidental Oral 0.49 16

Dermal Medium 0.31 X

Incidental Oral 0.30 27

Dermal Large 0.19 X

Incidental Oral 0.18 43

2596-50 

and 2596-

62:

Dog

Adult Dermal

2,770 Small 0.19 X

4,670 Large 0.089 X

Children

1 < 2

Dermal 2,770 Small 0.43 X

Incidental Oral 0.41 19

Dermal 4,670 Large 0.20 X

Incidental Oral 0.19 42

2596-83: 

Cat

Adult Dermal 1,750 Small 0.24 X

3,650 Large 0.19 X

Children

1 < 2

Dermal 1,750 Small 0.54 X

Incidental Oral 0.52 15

Dermal 3,650 Large 0.42 X

Incidental Oral 0.41 20

2596-139: 

Cat

Adult Dermal

1,460

Small 0.20 X

Medium 0.12 X

Large 0.076 X

Children

1 < 2

Dermal Small 0.45 X

Incidental Oral 0.44 18

Dermal Medium 0.27 X

Incidental Oral 0.26 31

Dermal Large 0.17 X

Incidental Oral 0.16 49

11556-164:

Dog

Adult Dermal

3,290

Small 0.23 X

Medium 0.098 X

Large 0.063 X

Children

1 < 2

Dermal Small 0.51 X

Incidental Oral 0.49 16

Dermal Medium 0.22 X

Incidental Oral 0.21 38

Dermal Large 0.14 X

Incidental Oral 0.13 60

11556-165: Adult Dermal 2,060 Small 0.29 X
Page 100 of 152

Table H.3. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Pet Collars (Solid Formulation). Incidental Oral LOC is an MOE 

= 1,000. 

EPA Reg. 

No./ 

Animal

Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Cat Medium 0.17 X

Large 0.11 X

Children

1 < 2

Dermal Small 0.63 X

Incidental Oral 0.61 13

Dermal Medium 0.38 X

Incidental Oral 0.37 22

Dermal Large 0.24 X

Incidental Oral 0.23 35

2596-84: 

Dog

Adult Dermal 2,770 Small 0.19 X

4,670 Large 0.089 X

Children

1 < 2

Dermal 2,770 Small 0.43 X

Incidental Oral 0.41 19

Dermal 4,670 Large 0.20 X

Incidental Oral 0.19 42

2596-139:

Dog

Adult Dermal

7,300

Small 0.51 X

Medium 0.22 X

Large 0.14 X

Children

1 < 2

Dermal Small 1.1 X

Incidental Oral 1.1 7.3

Dermal Medium 0.48 X

Incidental Oral 0.47 17

Dermal Large 0.31 X

Incidental Oral 0.30 27

2596-63: 

Cat

Adult Dermal

2,190 Small 0.31 X

2,480 Large 0.13 X

Children

1 < 2

Dermal 2,190 Small 0.68 X

Incidental Oral 0.65 12

Dermal 2,480 Large 0.29 X

Incidental Oral 0.28 29

1 Based on registered TCVP pet products as detailed in Table 4.0 of D426984.

2 Dose (mg/kg/day) equations provided in Appendix A of D426984.

3 MOE = Incidental Oral PoD (8.0 mg/kg/day) ÷ Dose (mg/kg/day).
Page 101 of 152

Table H.4. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Dust/Powder and Pump/Trigger Spray Formulations. 

Incidental Oral LOC is an MOE = 1,000.

EPA Reg. 

No./ Animal Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Dusts/Powders

47000-123:

Dog 

Adult Dermal

170 Small 0.0041 X

430 Medium 0.0044 X

680 Large 0.0044 X

Children

1 < 2

Dermal 

170 Small 

0.0090 X

Incidental Oral 0.0087 920

Dermal 

430 Medium

0.0096 X

Incidental Oral 0.0093 860

Dermal 

680 Large

0.0098 X

Incidental Oral 0.0095 840

47000-123:

Cat

Adult Dermal

43 Small 0.0020 X

100 Medium 0.0029 X

150 Large 0.0027 X

Children

1 < 2

Dermal 

43 Small 

0.0045 X

Incidental Oral 0.0043 1,800

Dermal 

100 Medium

0.0065 X

Incidental Oral 0.0063 1,300

Dermal 

150 Large

0.0061 X

Incidental Oral 0.0059 1,400

2596-78: 

Cat

Adult Dermal

280 Small 0.013 X

470 Large 0.0084 X

Children

1 < 2

Dermal 

280 Small

0.030 X

Incidental Oral 0.029 280

Dermal 

470 Large

0.019 X

Incidental Oral 0.018 450

2596-79:

Dog

Adult Dermal

470 Small 0.011 X

940 Medium 0.0096 X

1,200 Large 0.0076 X

Children

1 < 2

Dermal 

470 Small 

0.025 X

Incidental Oral 0.024 330

Dermal 

940 Medium

0.021 X

Incidental Oral 0.021 390

Dermal 

1,200 Large

0.017 X

Incidental Oral 0.016 490

67517-82:

Dog

Adult Dermal

510 Small 0.012 X

1,300 Medium 0.013 X

2,000 Large 0.013 X

Children

1 < 2

Dermal 

510 Small 

0.027 X

Incidental Oral 0.026 310

Dermal 1,300 Medium 0.029 X
Page 102 of 152

Table H.4. Residential Post-Application Non-Cancer (Steady State) Exposure and Risk 

Estimates from TCVP Dust/Powder and Pump/Trigger Spray Formulations. 

Incidental Oral LOC is an MOE = 1,000.

EPA Reg. 

No./ Animal Lifestage

Post-application 

Exposure Scenario

Application 

Rate

(mg ai)1

Animal

Size

Dose 

(mg/kg/day)2 MOEs3

Route of Exposure

Incidental Oral 0.028 290

Dermal 

2,000 Large

0.029 X

Incidental Oral 0.028 280

67517-82:

Cat

Adult Dermal

130 Small 0.0061 X

310 Medium 0.0088 X

460 Large 0.0082 X

Children

1 < 2

Dermal 

130 Small 

0.013 X

Incidental Oral 0.013 610

Dermal 

310 Medium

0.019 X

Incidental Oral 0.019 430

Dermal 

460 Large

0.018 X

Incidental Oral 0.018 450

Pump/Trigger Spray

2596-126, 140: 

Cat

(Trigger)

Adult Dermal

250 Small 0.0075 X

350 Large 0.0039 X

Children

1 < 2

Dermal 

250 Small

0.016 X

Incidental Oral 0.0017 4,700

Dermal 

350 Large

0.0086 X

Incidental Oral 0.00090 8,900

2596-140: Cat

(Pump)

Adult Dermal

51 Small 0.0015 X

71 Large 0.00080 X

Children

1 < 2

Dermal 

51 Small 

0.0034 X

Incidental Oral 0.00035 23,000

Dermal 

71 Large

0.0018 X

Incidental Oral 0.00018 43,000

2596-125, -140:

Dog

(Trigger)

Adult Dermal

350 Small 0.0052 X

400 Medium 0.0026 X

700 Large 0.0029 X

Children

1 < 2

Dermal 

350 Small 

0.012 X

Incidental Oral 0.0012 6,600

Dermal 

400 Medium

0.0056 X

Incidental Oral 0.00059 14,000

Dermal 

700 Large

0.0063 X

Incidental Oral 0.00066 12,000

1 Based on registered TCVP pet products as detailed in Table 4.0 of D426984.

2 Dose (mg/kg/day) equations provided in Appendix A of D426984.

3 MOE = Incidental Oral PoD (8.0 mg/kg/day) ÷ Dose (mg/kg/day).
Page 103 of 152

Appendix I. Summary of Residential Post-Application Cancer Exposure and Risks

Table I.1 Residential Post-Application Cancer Exposure and Risk Estimates from TCVP Pet 

Collar - Liquid Formulation

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

Amitraz Exposure Data (MRID 49468801)

2596-49: Cat

Small

Adult

9.1E-04 1.7E-06

Medium 5.4E-04 1.0E-06

Large 3.4E-04 6.2E-07

2596-50,62: Dog

Small 7.6E-04 1.4E-06

Large 3.5E-04 6.4E-07

2596-83: Cat

Small 9.6E-04 1.8E-06

Large 7.5E-04 1.4E-06

2596-139: Cat

Small 8.0E-04 1.5E-06

Medium 4.8E-04 8.8E-07

Large 3.0E-04 5.5E-07

11556-164: Dog

Small 9.0E-04 1.7E-06

Medium 3.9E-04 7.1E-07

Large 2.5E-04 4.5E-07

11556-165: Cat

Small 1.1E-03 2.1E-06

Medium 6.8E-04 1.2E-06

Large 4.2E-04 7.8E-07

2596-84: Dog

Small 7.6E-04 1.4E-06

Large 3.5E-04 6.4E-07

2596-139: Dog

Small 2.0E-03 3.7E-06

Medium 8.6E-04 1.6E-06

Large 5.5E-04 1.0E-06

2596-63: Cat

Small 1.2E-03 2.2E-06

Large 5.1E-04 9.4E-07

Davis, M., et al (2008)

2596-49: Cat

Small 5.8E-03 1.1E-05

Medium 3.5E-03 6.4E-06

Large 2.2E-03 4.0E-06

2596-50,62: Dog

Small 4.9E-03 8.9E-06

Large 2.2E-03 4.1E-06

2596-83: Cat

Small 6.2E-03 1.1E-05

Large 4.8E-03 8.8E-06
Page 104 of 152

Table I.1 Residential Post-Application Cancer Exposure and Risk Estimates from TCVP Pet 

Collar - Liquid Formulation

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

2596-139: Cat

Small 5.1E-03 9.4E-06

Medium 3.1E-03 5.6E-06

Large 1.9E-03 3.5E-06

11556-164: Dog

Small 5.8E-03 1.1E-05

Medium 2.5E-03 4.5E-06

Large 1.6E-03 2.9E-06

11556-165: Cat

Small 7.2E-03 1.3E-05

Medium 4.3E-03 7.9E-06

Large 2.7E-03 5.0E-06

2596-84: Dog

Small 4.9E-03 8.9E-06

Large 2.2E-03 4.1E-06

2596-139: Dog

Small 1.3E-02 2.3E-05

Medium 5.5E-03 1.0E-05

Large 3.5E-03 6.4E-06

2596-63: Cat

Small 7.7E-03 1.4E-05

Large 3.3E-03 6.0E-06
Page 105 of 152

Table I.2 Residential Post-Application Cancer Exposure and Risk Estimates from TCVP Pet 

Collar - Solid Formulation

Animal Type Animal Size Lifestage LADD1,2 Cancer Risk Estimate3

Amitraz Exposure Data (MRID 49468801)

2596-49: Cat

Small

Adult

2.4E-02 4.5E-05

Medium 1.5E-02 2.7E-05

Large 9.2E-03 1.7E-05

2596-50,62: Dog

Small 2.1E-02 3.8E-05

Large 9.4E-03 1.7E-05

2596-83: Cat

Small 2.6E-02 4.7E-05

Large 2.0E-02 3.7E-05

2596-139: Cat

Small 2.2E-02 4.0E-05

Medium 1.3E-02 2.4E-05

Large 8.1E-03 1.5E-05

11556-164: Dog

Small 2.4E-02 4.5E-05

Medium 1.0E-02 1.9E-05

Large 6.6E-03 1.2E-05

11556-165: Cat

Small 3.0E-02 5.6E-05

Medium 1.8E-02 3.3E-05

Large 1.1E-02 2.1E-05

2596-84: Dog

Small 2.1E-02 3.8E-05

Large 9.4E-03 1.7E-05

2596-139: Dog

Small 5.4E-02 9.9E-05

Medium 2.3E-02 4.2E-05

Large 1.5E-02 2.7E-05

2596-63: Cat

Small 3.2E-02 5.9E-05

Large 1.4E-02 2.5E-05
Page 106 of 152

Table I.3 Residential Post-Application Cancer Exposure and Risk Estimates from TCVP Pet 

Products

Animal Type Animal 

Size Lifestage LADD1,2 Cancer Risk Estimate3

Dust/Powder

47000-123: Dog

Small

Adult

5.9E-04 1.1E-06

Medium 6.3E-04 1.2E-06

Large 6.4E-04 1.2E-06

47000-123: Cat

Small 2.9E-04 5.4E-07

Medium 4.2E-04 7.8E-07

Large 4.0E-04 7.3E-07

2596-78: Cat

Small 1.9E-03 3.6E-06

Large 1.2E-03 2.2E-06

2596-79: Dog

Small 1.6E-03 3.0E-06

Medium 1.4E-03 2.5E-06

Large 1.1E-03 2.0E-06

67517-82: Dog

Small 1.8E-03 3.2E-06

Medium 1.9E-03 3.5E-06

Large 1.9E-03 3.5E-06

67517-82: Cat

Small 8.8E-04 1.6E-06

Medium 1.3E-03 2.3E-06

Large 1.2E-03 2.2E-06

Pump/Trigger Spray

2596-126, 140: Cat

(Trigger)

Small

Adult

5.3E-04 9.6E-07

Large 2.8E-04 5.1E-07

2596-140: Cat

(Pump)

Small 1.1E-04 2.0E-07

Large 5.6E-05 1.0E-07

2596-125, -140: Dog

(Trigger)

Small 3.7E-04 6.7E-07

Medium 1.8E-04 3.3E-07

Large 2.0E-04 3.7E-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 of D426984.

3 Cancer risk estimates = Total LADD × Q1*, where Q1* = 1.83 x 10-3 (mg/kg/day)-1
Page 107 of 152

Appendix J. Summary of Occupational Handler Exposures and Risks
Page 108 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Mixer/Loaders

(1a) Mixing/

Loading 

Liquids for 

Groundboom 

Applications

Poultry Buildings 

(Floors)

0.00077

(lb ai/

sq ft)

100,000

(sq ft/day)

2.5E-04 4.9E-05 2.5E-05 9.3E-05 20,000 100,000 200,000 94,000

Poultry Buildings 

(Floor Management, 

Fowl Tick)

0.00064 2.0E-04 4.1E-05 2.0E-05 7.7E-05 2,5000 120,000 250,000 110,000

Poultry Buildings 

(Flies Residual) 0.00013 4.1E-05 8.3E-06 4.1E-06 1.6E-05 120,000 600,000 1,200,000 550,000

Poultry Floor 

Management 0.000064 2.0E-05 4.1E-06 2.0E-06 7.7E-06 250,000 1,200,000 2,500,000 1,100,000

(1b) Mixing/

Loading 

Liquids for 

Paint 

Applications

Poultry Buildings

(Roost)

0.077

2 gallons

4.9E-07 9.8E-08 4.9E-08 1.9E-07 1.0E+07 5.1E+07 1.0E+08 4.7E+07

0.064

(lb ai/

gallon)

4.1E-07 8.1E-08 4.1E-08 1.5E-07 1.2E+07 6.1E+07 1.2E+08 5.6E+07

(2a) Mixing/

Loading 

Wettable 

Powders for 

Groundboom 

Applications

Poultry Buildings

(Including: 

Droppings, Floor 

Management Litter, 

Fowl Tick)

0.00080

(lb ai/

sq ft)

100,000 

sq ft

0.050 0.010 0.0050 0.00028 170 870 1,700 31,000

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

Other Animal 

Buildings

0.00032 0.0200 0.040 0.0020 0.00011 430 2,200 4,300 78,000

(2b, 2c) 

Mixing/

Loading 

Wettable 

Powders for 

Handheld 

fogger, and 

Stationary 

Fogger 

Applications

Poultry (Floor 

Management - 

Litter)

0.0016

(lb ai/

bird)

20,000 

birds 0.020 0.0040 0.0020 0.00011 430 2,200 4,300 78,000

0.00078

(lb ai/

sq ft) 100,000

sq ft

0.049 0.0097 0.0049 0.00027 180 890 1,800 32,000

0.00023 0.014 0.0029 0.0014 0.000080 610 3,000 6,100 110,000

(2d) Mixing/ 0.080 2 gallons 1.0E-04 2.0E-05 1.0E-05 5.6E-07 87,000 430,000 870,000 16,000,000
Page 109 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Loading 

Wettable 

Powders for 

Paint 

Applications

Poultry (Floor 

Management –

Roost)

(lb ai/

gallon)

(3a) Mixing/

Loading 

Dusts for 

Paint 

Applications

(WP Data as 

Surrogate)

0.030

(lb ai/

gallon)

3.7E-05 7.5E-06 3.7E-06 2.1E-07 230,000 1,200,000 2,300,000 41,000,000

Applicators

(4) 

Groundboom

Applications

Poultry Buildings

(Including: 

Droppings, Floor 

Management Litter, 

Fowl Tick, Garbage 

Piles, Manure Piles, 

Under Feed 

Troughs)

0.00080

(lb ai/

sq ft)

100,000

sq ft

3.9E-04 7.9E-05 3.9E-05 5.0E-05 6,300 31,000 63,000 170,000

Poultry Buildings 

(Including: Ceilings, 

Floors, Larvicide, 

Walls)

0.00077 3.8E-04 7.6E-05 3.8E-05 4.8E-05 6,500 33,000 65,000 180,000

Poultry Buildings 

(Including: Floor 

Management, Fowl 

Tick, Larvicide)

0.00064 3.2E-04 6.3E-05 3.2E-05 4.0E-05 7,800 39,000 78,000 220,000

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

Other Animal 

Buildings

0.00032 1.6E-04 3.2E-05 1.6E-05 2.0E-05 1,6000 78,000 160,000 430,000

Poultry Buildings 

(Flies Residual) 0.00013 6.4E-05 1.3E-05 6.4E-06 8.1E-06 39,000 190,000 390,000 1,100,000
Page 110 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Poultry (Floor 

Management) 0.000064 3.2E-05 6.3E-06 3.2E-06 4.0E-06 78,000 390,000 780,000 2,200,000

(5) Open 

Pour Liquid 

Additive for 

Feed Through 

Applications

Cattle Feed

(Concentrate)

0.0039

(lb ai/ 

animal) 1,000

cows

1.2E-05 2.5E-06 1.2E-06 No Data 400,000 2,000,000 4,000,000 No Data

Cattle Feed

(Concentrate) 0.0022 7.0E-06 1.4E-06 7.0E-07 No Data 710,000 3,600,000 7,100,000 No Data

Horse Feed 0.0017 500

horses 2.7E-06 5.4E-07 2.7E-07 No Data 1,800,000 9,300,000 18,000,000 No Data

Swine Feed 0.00060 6,250

pigs 1.2E-05 2.4E-06 1.2E-06 No Data 420,000 2,100,000 4,200,000 No Data

(6a) RTU Pet 

Collar 

Applications1

- Liquid 

Formulation

Cat (2596-49) 0.0036

8

animals

Inhalation exposures for the application of pet collar products are negligible. 

Dog (2596-50,62) -

Small 0.0061

Dog (2596-50,62) -

Large 0.010

Cat (2596-63) -

Small 0.0048

Cat (2596-63) -

Large 0.0055

Cat (2596-83) -

Small 0.0039

Cat (2596-83) -

Large 0.0080

Dog (2596-84) –

Small 0.0061

Dog (2596-84) –

Large 0.010

Cat (2596-139) - 

All 0.0032

Dog (2596-139) -

All 0.016

Dog (11556-164) -

All 0.0072

Cat (11556-165) -

All 0.0045

Cat (2596-49) 0.0036 0.504 0.101 0.0504 No Data 680 3400 6800 No Data
Page 111 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

(6b) RTU Pet 

Collar 

ApplicationsDust 

Formulation

Dog (2596-50,62) -

Small 0.0061 0.854 0.171 0.0854 No Data 400 2000 4000 No Data

Dog (2596-50,62) -

Large 0.010 1.4 0.28 0.14 No Data 250 1200 2500 No Data

Cat (2596-63) -

Small 0.0048 0.672 0.134 0.0672 No Data 510 2600 5100 No Data

Cat (2596-63) -

Large 0.0055 0.77 0.154 0.077 No Data 450 2200 4500 No Data

Cat (2596-83) -

Small 0.0039 0.546 0.109 0.0546 No Data 630 3200 6300 No Data

Cat (2596-83) -

Large 0.0080 1.12 0.224 0.112 No Data 310 1500 3100 No Data

Dog (2596-84) –

Small 0.0061 0.854 0.171 0.0854 No Data 400 2000 4000 No Data

Dog (2596-84) –

Large 0.010 1.4 0.28 0.14 No Data 250 1200 2500 No Data

Cat (2596-139) - 

All 0.0032 0.448 0.0896 0.0448 No Data 770 3800 7700 No Data

Dog (2596-139) -

All 0.016 2.24 0.448 0.224 No Data 150 770 1500 No Data

Dog (11556-164) -

All 0.0072 1.01 0.202 0.101 No Data 340 1700 3400 No Data

Cat (11556-165) -

All 0.0045 0.63 0.126 0.063 No Data 550 2700 5500 No Data

(7) RTU 

Dust/Powder

Applications 

Dog (47000-123) -

Small 0.00037 0.00075 0.00015 0.000075 No Data 6,600 33,000 66,000 No Data

Dog (47000-123) -

Medium 0.00094 0.0019 0.00038 0.00019 No Data 2,600 13,000 26,000 No Data

Dog (47000-123) -

Large 0.0015 0.0030 0.00061 0.00030 No Data 1,600 8,200 16,000 No Data

Cat (47000-123) -

Small 0.000090 0.00018 0.000037 0.000018 No Data 27,000 140,000 270,000 No Data

Cat (47000-123) -

Medium 0.00022 0.00045 0.000089 0.000045 No Data 11,000 56,000 110,000 No Data

Cat (47000-123) -

Large 0.00034 0.00069 0.00014 0.000069 No Data 7,200 36,000 72,000 No Data

Cat (2596-78) -

Small 0.00062 0.0013 0.00025 0.00013 No Data 4,000 20,000 40,000 No Data
Page 112 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Cat (2596-78) -

Large 0.0010 0.0020 0.00041 0.00020 No Data 2,500 12,000 25,000 No Data

Dog (2596-79) -

Small 0.0010 0.0020 0.00041 0.00020 No Data 2,500 12,000 25,000 No Data

Dog (2596-79) -

Medium 0.0021 0.0043 0.00085 0.00043 No Data 1,200 5,900 12,000 No Data

Dog (2596-79) -

Large 0.0026 0.0053 0.0011 0.00053 No Data 940 4,700 9,400 No Data

Dog (67517-82) -

Small 0.0011 0.0022 0.00045 0.00022 No Data 2,200 11,000 22,000 No Data

Dog (67517-82) -

Medium 0.0028 0.0057 0.0011 0.00057 No Data 880 4,400 8,800 No Data

Dog (67517-82) -

Large 0.0045 0.0091 0.0018 0.00091 No Data 550 2,700 5,500 No Data

Cat (67517-82) -

Small 0.00028 0.00057 0.00011 0.000057 No Data 8,800 44,000 88,000 No Data

Cat (67517-82) -

Medium 0.00067 0.0014 0.00027 0.00014 No Data 3,700 18,000 37,000 No Data

Cat (67517-82) -

Large 0.0010 0.0020 0.00041 0.00020 No Data 2,500 12,000 25,000 No Data

(8) RTU 

Pump/Trigger 

Spray 

Applications

Cat (2596-126,140) 

- Trigger -Small 0.00055 0.00021 0.000042 0.000021 No Data 24,000 120,000 240,000 No Data

Cat (2596-126,140) 

- Trigger - Large 0.00077 0.00029 0.000059 0.000029 No Data 17,000 85,000 170,000 No Data

Cat (2596-140) -

Pump - Small 0.00011 0.000042 0.0000084 0.0000042 No Data 120,000 590,000 1,200,000 No Data

Cat (2596-140) -

Pump - Large 0.00016 0.000061 0.000012 0.0000061 No Data 82,000 410,000 820,000 No Data

Dog (2596-125,-

140) - Small 0.00077 0.00029 0.000059 0.000029 No Data 17,000 85,000 170,000 No Data

Dog (2596-125,-

140) - Medium 0.00088 0.00034 0.000067 0.000034 No Data 15,000 74,000 150,000 No Data

Dog (2596-125,-

140) - Large 0.0015 0.00057 0.00012 0.000057 No Data 8,700 43,000 87,000 No Data

Mixers/Loaders/Applicators

Beef Cattle - Direct 

Applied 

0.039

(lb ai/

400

animals 0.0068 0.0014 0.00068 No Data 1,300 6,400 13,000 No Data
Page 113 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

(9a) Liquid: 

Backpack 

Sprayer

animal)

0.032 0.0056 0.0011 0.00056 No Data 1,600 7,800 16,000 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.032

(lb ai/

sq ft)

1,000

sq ft

(spot)

0.014 0.0028 0.0014 No Data 620 3,100 6,200 No Data

Beef Cattle - Direct 

Applied 

0.026

(lb ai/

animal)

400 

animals

0.0045 0.00090 0.00045 No Data 1,900 9,600 19,000 No Data

Swine - Direct 

Applied 0.049 0.0085 0.0017 0.00085 No Data 1,000 5,100 10,000 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0049 0.00085 0.00017 0.000085 No Data 10,000 51,000 100,000 No Data

0.0013 0.00023 0.000045 0.000023 No Data 38,000 190,000 380,000 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) 

0.00077

lb ai/

sq ft

20,000

sq ft

0.0067 0.0013 0.00067 No Data 1,300 6,500 13,000 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 0.0056 0.0011 0.00056 No Data 1,600 7,800 16,000 No Data

Poultry (Caged) -

Direct Applied 

0.00032

lb ai/

bird

20,000

birds 0.0028 0.00056 0.00028 No Data 3,100 16,000 31,000 No Data

Poultry Buildings 

(Flies Residual) -

0.00013 20,000

sq ft 0.0011 0.00023 0.00011 No Data 3,300 17,000 33,000 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 0.00068 0.00014 0.000068 No Data 7,700 38,000 77,000 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 0.00056 0.00011 0.000056 No Data 13,000 64,000 130,000 No Data

(9b) Liquid: Beef Cattle - Direct 

Applied 

0.039

(lb ai/

400

animals 0.0068 0.0014 0.00068 No Data 1,300 6,400 13,000 No Data
Page 114 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

ManuallyPressurized 

Handwand

animal)

0.032 0.0056 0.0011 0.00056 No Data 1,600 7,800 16,000 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.032

(lb ai/

sq ft)

1,000

sq ft

(spot)

0.0139 0.0028 0.0014 No Data 620 3,100 6,200 No Data

Beef Cattle - Direct 

Applied 

0.026

(lb ai/

animal)

400 

animals

0.0045 0.00090 0.00045 No Data 1,900 9,600 19,000 No Data

Swine - Direct 

Applied 0.049 0.0085 0.0017 0.00085 No Data 1,000 5,100 10,000 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0049 0.00085 0.00017 0.000085 No Data 10,000 51,000 100,000 No Data

0.0013 0.00023 0.00045 0.000023 No Data 38,000 190,000 380,000 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) -

0.00077

lb ai/

sq ft

20,000

sq ft

0.0067 0.0013 0.00067 No Data 1,300 6,500 13,000 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 0.0056 0.0011 0.00056 No Data 1,600 7,800 16,000 No Data

Poultry (Caged) -

Direct Applied 

0.00031

lb ai/

bird

20,000

birds 0.0027 0.00054 0.00027 No Data 3,200 16,000 32,000 No Data

Poultry Buildings 

(Flies Residual) -

0.00013 20,000

sq ft 0.0011 0.00023 0.00011 No Data 7,700 38,000 77,000 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 0.00068 0.00014 0.000068 No Data 13,000 64,000 130,000 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 0.00056 0.00011 0.000056 No Data 16,000 78,000 160,000 No Data

(9c) Liquid: Beef Cattle - Direct 

Applied 

0.039

(lb ai/

400 

animals 0.018 0.0036 0.0018 No Data 490 2,400 4,900 No Data
Page 115 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Mechanically

-Pressurized 

Handgun

animal)

0.032 0.015 0.0029 0.0015 No Data 590 3,000 5,900 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.026

(lb ai/

animal)

0.012 0.0024 0.0012 No Data 730 3,600 7,300 No Data

Beef Cattle - Direct 

Applied 0.049 0.023 0.0045 0.0023 No Data 380 1,900 3,800 No Data

Swine - Direct 

Applied 0.0049 0.0023 0.00045 0.00023 No Data 3,800 19,000 38,000 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0013 0.00060 0.00012 0.000060 No Data 15,000 73,000 150,000 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) -

0.00077

lb ai/

sq ft

20,000

sq ft

0.018 0.0035 0.0018 No Data 490 2,500 4,900 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 0.015 0.0029 0.0015 No Data 590 3,000 5,900 No Data

Poultry (Caged) -

Direct Applied 

0.00032

lb ai/

bird

20,000

birds 0.0073 0.0015 0.00073 No Data 1,200 5,900 12,000 No Data

Poultry Buildings 

(Flies Residual) 0.00013 20,000sq ft 0.0030 0.00060 0.00023 No Data 2,900 15,000 29,000 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 0.0018 0.00036 0.00018 No Data 4,900 24,000 49,000 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 0.0015 0.00029 0.00015 No Data 5,900 30,000 59,000 No Data

(9d) Liquid:

Backrubber 

or Facerubber

Cattle - Direct 

Applied

0.077

(lb ai/

gallon)

50 

(gallons/

day)

0.000012 0.0000025 0.0000012 No Data 410,000 2,000,000 4,100,000 No Data
Page 116 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

0.064 0.000010 0.0000020 0.0000010 No Data 490,000 2,500,000 4,900,000 No Data

(10a) 

Wettable 

Powder: 

Backpack 

Sprayer

Beef Cattle - Direct 

Spray 0.040

400 

animals

0.0070 0.0014 0.00070 No Data 1,200 6,200 12,000 No Data

Swine - Direct 

Spray 0.020 0.0035 0.00070 0.00035 No Data 2,500 12,000 25,000 No Data

Poultry (Floor 

Management Litter, 

Fowl Tick), Poultry 

Droppings, Manure 

Piles, Garbage Piles, 

Under Feed Troughs 

0.00080 20,000

sq ft 0.0070 0.0014 0.00070 No Data 1,200 6,200 12,000 No Data

Poultry (Wire 

Cages) - Direct 

Spray 

0.00040 20,000

birds 0.0035 0.00070 0.00035 No Data 2,500 12,000 25,000 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.00032

20,000

sq ft

0.0028 0.00056 0.00028 No Data 3,100 16,000 31,000 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.00016 0.0014 0.00028 0.00014 No Data 6,200 31,000 62,000 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal

Buildings

0.000080 0.00070 0.00014 0.000070 No Data 12,000 62,000 120,000 No Data

Kennels, Yards, 

Campgrounds, 

Picnic Areas, and 

Recreational Parks

0.000040

1,000

sq ft

(spot)

0.000017 0.0000035 0.0000017 No Data 500,000 2,500,000 5,000,000 No Data

(10b) 

Wettable

Powder:

Beef Cattle - Direct 

Spray 0.040

400 

animals

0.0067 0.0014 0.00070 No Data 1,200 6,200 12,000 No Data

Swine - Direct 

Spray 0.020 0.0035 0.00070 0.00035 No Data 2,500 12,000 25,000 No Data
Page 117 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

ManuallyPressurized 

Handwand

Poultry (Floor 

Management Litter, 

Fowl Tick), Poultry 

Droppings, Manure 

Piles, Garbage Piles, 

Under Feed Troughs 

0.00080 20,000

sq ft 0.0070 0.0014 0.00070 No Data 1,200 6,200 12,000 No Data

Poultry (Wire 

Cages) - Direct 

Spray 

0.00040 20,000

birds 0.0035 0.00070 0.00035 No Data 2,500 12,000 25,000 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.00032

20,000

sq ft

0.0028 0.00056 0.00028 No Data 3,100 16,000 31,000 No Data

0.00016 0.0014 0.00028 0.00014 No Data 6,200 31,000 62,000 No Data

0.000080 0.00070 0.00014 0.000070 No Data 12,000 62,000 120,000 No Data

Kennels, Yards, 

Campgrounds, 

Picnic Areas, and 

Recreational Parks

0.000040

1,000

sq ft

(spot)

0.000017 0.0000035 0.0000017 No Data 500,000 2,500,000 5,000,000 No Data

(10d and 10e) 

Wettable 

Powder: 

Handheld 

Fogger and 

Stationary 

Fogger

Poultry (Floor 

Management) 

0.0016

lb ai/

bird

20,000 

birds

No exposure data available for these use patterns. 0.00078

lb ai/

sq ft 20,000

sq ft Poultry (Floor 

Management Litter) 0.00023

(10f)

Wettable 

Powder: 

Rotary Duster 

(Dust -

Plunger Data 

as Surrogate)

Poultry (Floor 

Management Litter)

0.00023

lb ai/

sq ft

20,000

sq ft 0.11 0.023 0.011 No Data 44 220 440 No Data

(10g) 

Wettable 

Powder: 

Plunger 

Duster (Dust 

Poultry (Floor 

Management) 

0.0016

lb ai/

bird

1,000 

birds 0.039 0.0078 0.0039 No Data 130 640 1,300 No Data

0.00078

lb ai/

1,000

sq ft 0.019 0.0038 0.0019 No Data 260 1,300 2,600 No Data
Page 118 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

Data as 

Surrogate)

sq ft

Poultry (Floor 

Management Litter) 0.00023 0.0056 0.0011 0.00056 No Data 880 4,400 8,800 No Data

(11a) Dust:

Self-Treating 

Dust Bag

Cattle

0.75

lb ai/

dust bag 10 

dust bags

0.18 0.037 0.018 No Data 27 140 270 No Data

0.38 0.093 0.019 0.0093 No Data 54 270 540 No Data

0.13 0.032 0.0064 0.0032 No Data 160 780 1,600 No Data

(11b) Dust:

Shaker Can

Cattle, Swine –

Direct Applied 

0.0075

(lb ai

/animal) 400 

animals

0.76 0.15 0.076 No Data 6.6 33 66 No Data

0.0038 0.39 0.077 0.039 No Data 13 65 130 No Data

Cattle – Direct 

Applied 0.0013 0.13 0.026 0.013 No Data 38 190 380 No Data

Poultry (Dust Box) 

– Direct Applied

0.00060

(lb ai/ 

bird)

1,000

birds 0.15 0.030 0.015 No Data 33 160 330 No Data

Poultry (Floor 

Management)

0.00030

(lb ai/ 

sq ft)

1,000 

sq ft

0.076 0.015 0.0076 No Data 66 330 660 No Data

Swine - Bedding 0.00020 0.051 0.010 0.0051 No Data 98 490 980 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 1,000birds 0.025 0.0051 0.0025 No Data 200 980 2,000 No Data

(11c) Dust:

Rotary Duster

(Plunger Data 

as Surrogate)

Cattle, Swine –

Direct Applied 

0.0075

(lb ai

/animal) 400

animals

0.074 0.015 0.0074 No Data 68 340 680 No Data

0.0038 0.037 0.0075 0.0037 No Data 130 670 1,300 No Data

Cattle – Direct 

Applied 0.0013 0.013 0.0026 0.0013 No Data 390 2,000 3,900 No Data

Poultry (Dust Box) 

– Direct Applied

0.00060

lb ai/

bird

20,000

birds 0.29 0.060 0.029 No Data 17 85 170 No Data

Poultry (Floor 

Management) 0.00030 20,000sq ft 0.15 0.029 0.015 No Data 34 170 340 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 20,000birds 0.049 0.0098 0.0049 No Data 100 510 1,000 No Data
Page 119 of 152

Table J.1. TCVP Occupational Handler Non-Cancer (Steady State) Risk Estimates. 

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Inhalation Dose (mg/kg/day) Inhalation MOEs

(LOC is an MOE = 300)

No R PF5 R PF10 R EC No R PF5 R PF10 R EC

(11d) Dust:

Plunger 

Duster

Poultry (Dust Box) 

– Direct Applied

0.00060

lb ai/

bird

1,000

birds 0.015 0.0029 0.0015 No Data 340 1,700 3,400 No Data

Poultry (Floor 

Management) 0.00030 1,000sq ft 0.0074 0.0015 0.00074 No Data 680 3,400 6,800 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 1,000birds 0.0025 0.00049 0.00025 No Data 2,000 10,000 20,000 No Data

(12a) Paint: 

Brush or 

Roller

Poultry (Roost 

Paint) 

0.08 

lb ai/

gallon

2 gallons

0.00065 0.00013 0.000065 No Data 13,000 67,000 130,000 No Data

0.077 0.00063 0.00013 0.000063 No Data 14,000 69,000 140,000 No Data

0.064 0.00052 0.00010 0.000052 No Data 17,000 83,000 170,000 No Data

0.03 0.00024 0.000049 0.000024 No Data 36,000 180,000 360,000 No Data

(12b) Paint: 

Airless 

Poultry (Roost 

Paint) 

0.08 

lb ai/

gallon

2 gallons

0.0013 0.00026 0.00013 No Data 3,800 19,000 38,000 No Data

0.077 0.0013 0.00025 0.00013 No Data 4,000 20,000 40,000 No Data

0.064 0.0010 0.00021 0.00010 No Data 4,800 24,000 48,000 No Data

0.03 0.00049 0.000097 0.000049 No Data 10,000 51,000 100,000 No Data

(13) 

Solid Feed 

Additive for 

Feed Through 

Applications 

via Cup

(Granular 

Data as 

Surrogate)

Horse Feed

0.0015

(lb ai/

animal)

500 

horses

0.00014 0.000027 0.000014 No Data 37,000 180,000 370,000 No Data

0.00077 0.000070 0.000014 0.0000070 No Data 72,000 360,000 720,000 No Data

Cattle Feed

0.0022

1,000 

cows

0.00040 0.000080 0.000040 No Data 13,000 63,000 130,000 No Data

0.0017 0.00031 0.000062 0.000031 No Data 16,000 81,000 160,000 No Data
Page 120 of 152

Appendix K. Summary of Occupational Handler Cancer Risk Estimates
Page 121 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Mixer/Loaders

(1a) Mixing/

Loading 

Liquids for 

Groundboom 

Applications

Poultry Buildings 

(Including: Ceilings, 

Floors, Larvicide, 

Walls)

0.00077

(lb ai/

sq ft)

100,000

(sq ft/day)

5E-07 9E-08 7E-08 5E-07 9E-08 7E-08 5E-07 9E-08 7E-08 2E-08

Poultry Buildings 

(Including: Floor 

Management, Fowl 

Tick, Larvicide)

0.00064 4E-07 8E-08 6E-08 4E-07 8E-08 6E-08 4E-07 7E-08 6E-08 2E-08

Poultry Buildings 

(Flies Residual) 0.00013 9E-08 2E-08 1E-08 9E-08 2E-08 1E-08 9E-08 2E-08 1E-08 4E-09

Poultry Floor 

Management 0.000064 4E-08 8E-09 6E-09 4E-08 8E-09 6E-09 4E-08 7E-09 6E-09 2E-09

(1b) Mixing/

Loading 

Liquids for 

Paint 

Applications

Poultry Buildings

(Roost)

0.077

2 gallons

1E-09 2E-10 1E-10 1E-09 2E-10 1E-10 1E-09 2E-10 1E-10 5E-11

0.064

(lb ai/

gallon)

9E-10 2E-10 1E-10 9E-10 2E-10 1E-10 9E-10 1E-10 1E-10 4E-11

(2a) Mixing/

Loading 

Wettable 

Powders for 

Groundboom 

Applications

Poultry Buildings

(Including: 

Droppings, Floor 

Management Litter, 

Fowl Tick, Garbage 

Piles, Manure Piles, 

Under Feed 

Troughs)

0.00080

(lb ai/

sq ft)

100,000 

sq ft

1E-05 2E-06 1E-06 9E-06 6E-07 5E-07 9E-06 5E-07 4E-07 3E-08

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

Other Animal 

Buildings

0.00032 4E-06 6E-07 6E-07 4E-06 3E-07 2E-07 4E-06 2E-07 2E-07 1E-08

(2b, 2c) 

Mixing/

Loading 

Wettable 

Powders for 

Handheld 

Poultry (Floor 

Management - 

Litter)

0.0016

(lb ai/

bird)

20,000 

birds 4E-06 6E-07 6E-07 4E-06 3E-07 2E-07 4E-06 2E-07 2E-07 1E-08

0.00078

(lb ai/

sq ft)

100,000

sq ft 1E-05 1E-06 1E-06 9E-06 6E-07 5E-07 9E-06 5E-07 4E-07 3E-08
Page 122 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Fogger, and 

Stationary 

Fogger 

Applications

0.00023 3E-06 4E-07 4E-07 3E-06 2E-07 2E-07 3E-06 2E-07 1E-07 9E-09

(2d) Mixing/

Loading 

Wettable 

Powders for 

Paint 

Applications Poultry (Floor 

Management –

Roost)

0.080

(lb ai/

gallon)

2 gallons

2E-08 3E-09 3E-09 2E-08 1E-09 1E-09 2E-08 1E-09 9E-10 6E-11

(3a) Mixing/

Loading 

Dusts for 

Paint 

Applications

(WP Data as 

Surrogate)

0.030

(lb ai/

gallon)

8E-09 1E-09 1E-09 7E-09 5E-10 4E-10 7E-09 4E-10 3E-10 2E-11

Applicators

(4) 

Groundboom

Applications

Poultry Buildings

(Including: 

Droppings, Floor 

Management Litter, 

Fowl Tick, Garbage 

Piles, Manure Piles, 

Under Feed 

Troughs)

0.00080

(lb ai/

sq ft)

100,000

sq ft

2E-07 5E-08 4E-08 2E-07 4E-08 3E-08 2E-07 4E-08 3E-08 1E-08

Poultry Buildings 

(Including: Ceilings, 

Floors, Larvicide, 

Walls)

0.00077 2E-07 5E-08 4E-08 2E-07 4E-08 3E-08 2E-07 4E-08 3E-08 1E-08

Poultry Buildings 

(Including: Floor 

Management, Fowl 

Tick, Larvicide)

0.00064 2E-07 4E-08 3E-08 2E-07 3E-08 3E-08 2E-07 3E-08 3E-08 1E-08

Dairy Barns, 

Poultry Houses, 0.00032 8E-08 2E-08 2E-08 8E-08 2E-08 1E-08 8E-08 2E-08 1E-08 5E-09
Page 123 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Swine Barns, or 

Other Animal 

Buildings

Poultry Buildings 

(Flies Residual) 0.00013 3E-08 8E-09 6E-09 3E-08 7E-09 5E-09 3E-08 7E-09 5E-09 2E-09

Poultry (Floor 

Management) 0.000064 2E-08 4E-09 3E-09 2E-08 3E-09 3E-09 2E-08 3E-09 3E-09 1E-09

(5) Open 

Pour Liquid 

Additive for 

Feed Through 

Applications

Cattle Feed

(Concentrate)

0.0039

(lb ai/ 

animal) 1,000

cows

3E-08 5E-09 4E-09 3E-08 5E-09 4E-09 3E-08 5E-09 3E-09 No Data

Cattle Feed

(Concentrate) 0.0022 2E-08 3E-09 2E-09 1E-08 3E-09 2E-09 1E-08 3E-09 2E-09 No Data

Horse Feed 0.0017 500

horses 6E-09 1E-09 8E-10 6E-09 1E-09 8E-10 6E-09 1E-09 8E-10 No Data

Swine Feed 0.00060 6,250

pigs 3E-08 5E-09 4E-09 3E-08 4E-09 3E-09 3E-08 4E-09 3E-09 No Data

(6a) RTU Pet 

Collar 

Applications

- Liquid 

Formulation

Cat (2596-49) 0.0036

8

animals

1E-07 6E-08 4E-08 No Data No Data No Data No Data No Data No Data No Data

Dog (2596-50,62) -

Small 0.0061 2E-07 1E-07 6E-08 No Data No Data No Data No Data No Data No Data No Data

Dog (2596-50,62) -

Large 0.010 3E-07 2E-07 1E-07 No Data No Data No Data No Data No Data No Data No Data

Cat (2596-63) -

Small 0.0048 1E-07 8E-08 5E-08 No Data No Data No Data No Data No Data No Data No Data

Cat (2596-63) -

Large 0.0055 2E-07 9E-08 6E-08 No Data No Data No Data No Data No Data No Data No Data

Cat (2596-83) -

Small 0.0039 1E-07 7E-08 4E-08 No Data No Data No Data No Data No Data No Data No Data

Cat (2596-83) -

Large 0.0080 2E-07 1E-07 8E-08 No Data No Data No Data No Data No Data No Data No Data

Dog (2596-84) –

Small 0.0061 2E-07 1E-07 6E-08 No Data No Data No Data No Data No Data No Data No Data

Dog (2596-84) –

Large 0.010 3E-07 2E-07 1E-07 No Data No Data No Data No Data No Data No Data No Data

Cat (2596-139) - 

All 0.0032 9E-08 5E-08 3E-08 No Data No Data No Data No Data No Data No Data No Data

Dog (2596-139) -

All 0.016 4E-07 3E-07 2E-07 No Data No Data No Data No Data No Data No Data No Data
Page 124 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Dog (11556-164) -

All 0.0072 2E-07 1E-07 7E-08 No Data No Data No Data No Data No Data No Data No Data

Cat (11556-165) -

All 0.0045 1E-07 8E-08 5E-08 No Data No Data No Data No Data No Data No Data No Data

(6b) RTU Pet 

Collar 

Applications

- Dust 

Formulation

Cat (2596-49) 0.0036 4E-06 3E-07 2E-07 4E-06 1E-07 1E-07 4E-06 1E-07 8E-08 No Data

Dog (2596-50,62) -

Small 0.0061 6E-06 4E-07 4E-07 6E-06 2E-07 2E-07 6E-06 2E-07 1E-07 No Data

Dog (2596-50,62) -

Large 0.010 1E-05 7E-07 6E-07 1E-05 4E-07 3E-07 1E-05 3E-07 2E-07 No Data

Cat (2596-63) -

Small 0.0048 5E-06 3E-07 3E-07 5E-06 2E-07 1E-07 5E-06 2E-07 1E-07 No Data

Cat (2596-63) -

Large 0.0055 6E-06 4E-07 3E-07 6E-06 2E-07 1E-07 6E-06 2E-07 1E-07 No Data

Cat (2596-83) -

Small 0.0039 4E-06 3E-07 2E-07 4E-06 1E-07 1E-07 4E-06 1E-07 9E-08 No Data

Cat (2596-83) -

Large 0.0080 8E-06 6E-07 5E-07 8E-06 3E-07 2E-07 8E-06 3E-07 2E-07 No Data

Dog (2596-84) –

Small 0.0061 6E-06 4E-07 4E-07 6E-06 2E-07 2E-07 6E-06 2E-07 1E-07 No Data

Dog (2596-84) –

Large 0.010 1E-05 7E-07 6E-07 1E-05 4E-07 3E-07 1E-05 3E-07 2E-07 No Data

Cat (2596-139) - 

All 0.0032 3E-06 2E-07 2E-07 3E-06 1E-07 9E-08 3E-06 1E-07 7E-08 No Data

Dog (2596-139) -

All 0.016 2E-05 1E-06 1E-06 2E-05 6E-07 4E-07 2E-05 5E-07 4E-07 No Data

Dog (11556-164) -

All 0.0072 8E-06 5E-07 5E-07 7E-06 3E-07 2E-07 7E-06 2E-07 2E-07 No Data

Cat (11556-165) -

All 0.0045 5E-06 3E-07 3E-07 5E-06 2E-07 1E-07 5E-06 1E-07 1E-07 No Data

(7) RTU 

Dust/Powder

Applications 

Dog (47000-123) -

Small 0.00037 4E-07 3E-08 2E-08 4E-07 1E-08 1E-08 4E-07 1E-08 8E-09 No Data

Dog (47000-123) -

Medium 0.00094 1E-06 7E-08 6E-08 9E-07 3E-08 3E-08 9E-07 3E-08 2E-08 No Data
Page 125 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Dog (47000-123) -

Large 0.0015 2E-06 1E-07 9E-08 2E-06 5E-08 4E-08 2E-06 5E-08 3E-08 No Data

Cat (47000-123) -

Small 0.000090 9E-08 6E-09 6E-09 9E-08 3E-09 2E-09 9E-08 3E-09 2E-09 No Data

Cat (47000-123) -

Medium 0.00022 2E-07 2E-08 1E-08 2E-07 8E-09 6E-09 2E-07 7E-09 5E-09 No Data

Cat (47000-123) -

Large 0.00034 4E-07 2E-08 2E-08 3E-07 1E-08 9E-09 3E-07 1E-08 8E-09 No Data

Cat (2596-78) -

Small 0.00062 6E-07 4E-08 4E-08 6E-07 2E-08 2E-08 6E-07 2E-08 1E-08 No Data

Cat (2596-78) -

Large 0.0010 1E-06 7E-08 6E-08 1E-06 4E-08 3E-08 1E-06 3E-08 2E-08 No Data

Dog (2596-79) -

Small 0.0010 1E-06 7E-08 6E-08 1E-06 4E-08 3E-08 1E-06 3E-08 2E-08 No Data

Dog (2596-79) -

Medium 0.0021 2E-06 2E-07 1E-07 2E-06 8E-08 6E-08 2E-06 7E-08 5E-08 No Data

Dog (2596-79) -

Large 0.0026 3E-06 2E-07 2E-07 3E-06 9E-08 7E-08 3E-06 8E-08 6E-08 No Data

Dog (67517-82) -

Small 0.0011 1E-06 8E-08 7E-08 1E-06 4E-08 3E-08 1E-06 3E-08 2E-08 No Data

Dog (67517-82) -

Medium 0.0028 3E-06 2E-07 2E-07 3E-06 1E-07 8E-08 3E-06 9E-08 6E-08 No Data

Dog (67517-82) -

Large 0.0045 5E-06 3E-07 3E-07 5E-06 2E-07 1E-07 5E-06 1E-07 1E-07 No Data

Cat (67517-82) -

Small 0.00028 3E-07 2E-08 2E-08 3E-07 1E-08 8E-09 3E-07 9E-09 6E-09 No Data

Cat (67517-82) -

Medium 0.00067 7E-07 5E-08 4E-08 7E-07 2E-08 2E-08 7E-07 2E-08 2E-08 No Data

Cat (67517-82) -

Large 0.0010 1E-06 7E-08 6E-08 1E-06 4E-08 3E-08 1E-06 3E-08 2E-08 No Data

(8) RTU 

Pump/Trigger 

Spray 

Applications

Cat (2596-126,140) 

- Trigger -Small 0.00055 8E-08 7E-08 4E-08 7E-08 7E-08 4E-08 7E-08 7E-08 4E-08 No Data

Cat (2596-126,140) 

- Trigger - Large 0.00077 1E-07 1E-07 6E-08 1E-07 1E-07 5E-08 1E-07 1E-07 5E-08 No Data

Cat (2596-140) -

Pump - Small 0.00011 2E-08 1E-08 8E-09 1E-08 1E-08 8E-09 1E-08 1E-08 7E-09 No Data
Page 126 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Cat (2596-140) -

Pump - Large 0.00016 2E-08 2E-08 1E-08 2E-08 2E-08 1E-08 2E-08 2E-08 1E-08 No Data

Dog (2596-125,-

140) - Small 0.00077 1E-07 1E-07 6E-08 1E-07 1E-07 5E-08 1E-07 1E-07 5E-08 No Data

Dog (2596-125,-

140) - Medium 0.00088 1E-07 1E-07 7E-08 1E-07 1E-07 6E-08 1E-07 1E-07 6E-08 No Data

Dog (2596-125,-

140) - Large 0.0015 2E-07 2E-07 1E-07 2E-07 2E-07 1E-07 2E-07 2E-07 1E-07 No Data

Mixers/Loaders/Applicators

(9a) Liquid: 

Backpack 

Sprayer

Beef Cattle - Direct 

Applied 

0.039

(lb ai/

animal)

400

animals

4E-06 4E-06 2E-06 4E-06 4E-06 2E-06 4E-06 4E-06 2E-06 No Data

0.032 1E-06 1E-06 8E-07 1E-06 1E-06 7E-07 1E-06 1E-06 6E-07 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.032

(lb ai/

sq ft)

1,000

sq ft

(spot)

3E-06 3E-06 2E-06 3E-06 3E-06 2E-06 3E-06 2E-06 2E-06 No Data

Beef Cattle - Direct 

Applied 

0.026

(lb ai/

animal)

400 

animals

9E-07 9E-07 6E-07 8E-07 8E-07 5E-07 8E-07 8E-07 5E-07 No Data

Swine - Direct 

Applied 0.049 2E-06 2E-06 1E-06 2E-06 2E-06 1E-06 2E-06 2E-06 1E-06 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0049 2E-07 2E-07 1E-07 2E-07 2E-07 1E-07 2E-07 2E-07 1E-07 No Data

0.0013 5E-08 5E-08 3E-08 4E-08 4E-08 3E-08 4E-08 4E-08 3E-08 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) 

0.00077

lb ai/

sq ft

20,000

sq ft

1E-06 1E-06 9E-07 1E-06 1E-06 8E-07 1E-06 1E-06 8E-07 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 1E-06 1E-06 8E-07 1E-06 1E-06 7E-07 1E-06 1E-06 6E-07 No Data

Poultry (Caged) -

Direct Applied 

0.00031

lb ai/

20,000

birds 6E-07 6E-07 4E-07 5E-07 5E-07 3E-07 5E-07 5E-07 3E-07 No Data
Page 127 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

bird

Poultry Buildings 

(Flies Residual) -

0.00013 20,000

sq ft 5E-07 5E-07 4E-07 5E-07 5E-07 3E-07 5E-07 5E-07 3E-07 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 2E-07 2E-07 2E-07 2E-07 2E-07 1E-07 2E-07 2E-07 1E-07 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 1E-07 1E-07 9E-08 1E-07 1E-07 8E-08 1E-07 1E-07 8E-08 No Data

(9b) Liquid:

ManuallyPressurized 

Handwand

Beef Cattle - Direct 

Applied 

0.039

(lb ai/

animal)

400

animals

5E-05 4E-07 3E-07 5E-05 2E-07 2E-07 5E-05 2E-07 2E-07 No Data

0.032 4E-05 3E-07 3E-07 4E-05 2E-07 2E-07 4E-05 2E-07 2E-07 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.032

(lb ai/

sq ft)

1,000

sq ft

(spot)

1E-04 7E-07 7E-07 1E-04 5E-07 4E-07 1E-04 5E-07 4E-07 No Data

Beef Cattle - Direct 

Applied 

0.026

(lb ai/

animal)

400 

animals

3E-05 2E-07 2E-07 3E-05 2E-07 1E-07 3E-05 1E-07 1E-07 No Data

Swine - Direct 

Applied 0.049 6E-05 4E-07 4E-07 6E-05 3E-07 3E-07 6E-05 3E-07 2E-07 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0049 6E-06 4E-08 4E-08 6E-06 3E-08 3E-08 6E-06 3E-08 2E-08 No Data

0.0013 2E-06 1E-08 1E-08 2E-06 8E-09 7E-09 2E-06 7E-09 6E-09 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) -

0.00077

lb ai/

sq ft

20,000

sq ft

5E-05 4E-07 3E-07 5E-05 2E-07 2E-07 5E-05 2E-07 2E-07 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 4E-05 3E-07 3E-07 4E-05 2E-07 2E-07 4E-05 2E-07 2E-07 No Data
Page 128 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Poultry (Caged) -

Direct Applied 

0.00031

lb ai/

bird

20,000

birds 2E-05 1E-07 1E-07 2E-05 1E-07 8E-08 2E-05 9E-08 8E-08 No Data

Poultry Buildings 

(Flies Residual) -

0.00013 20,000

sq ft 2E-05 1E-07 1E-07 2E-05 9E-08 8E-08 2E-05 9E-08 7E-08 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 8E-06 6E-08 5E-08 8E-06 4E-08 3E-08 8E-06 4E-08 3E-08 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 5E-06 4E-08 3E-08 5E-06 2E-08 2E-08 5E-06 2E-08 2E-08 No Data

(9c) Liquid:

Mechanically

-Pressurized 

Handgun

Beef Cattle - Direct 

Applied 

0.039

(lb ai/

animal)

400 

animals

1E-06 7E-07 6E-07 9E-07 4E-07 3E-07 9E-07 3E-07 2E-07 No Data

0.032 1E-06 6E-07 5E-07 8E-07 3E-07 2E-07 7E-07 3E-07 2E-07 No Data

Woody Borders of 

Kennels, Yards, 

Campgrounds, 

Recreational Parks, 

Footpaths and 

Roadways 

0.026

(lb ai/

animal)

8E-07 5E-07 4E-07 6E-07 3E-07 2E-07 6E-07 2E-07 1E-07 No Data

Beef Cattle - Direct 

Applied 0.049 2E-06 9E-07 7E-07 1E-06 5E-07 3E-07 1E-06 4E-07 3E-07 No Data

Swine - Direct 

Applied 0.0049 2E-07 9E-08 7E-08 1E-07 5E-08 3E-08 1E-07 4E-08 3E-08 No Data

Lactating Dairy 

Cattle - Direct 

Applied 

0.0013 4E-08 2E-08 2E-08 3E-08 1E-08 8E-09 3E-08 1E-08 7E-09 No Data

Poultry Buildings 

(Walls, Ceilings, 

Floors, Larvicide) -

0.00077

lb ai/

sq ft

20,000

sq ft

1E-06 7E-07 6E-07 9E-07 4E-07 3E-07 9E-07 3E-07 2E-07 No Data

Poultry Buildings 

(Floor Management, 

Fowl Tick, 

Larvicide) 

0.00064 1E-06 6E-07 5E-07 8E-07 3E-07 2E-07 7E-07 3E-07 2E-07 No Data
Page 129 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Poultry (Caged) -

Direct Applied 

0.00031

lb ai/

bird

20,000

birds 5E-07 3E-07 2E-07 4E-07 2E-07 1E-07 4E-07 1E-07 9E-08 No Data

Poultry Buildings 

(Flies Residual) 0.00013 20,000sq ft 5E-07 3E-07 2E-07 4E-07 1E-07 1E-07 3E-07 1E-07 8E-08 No Data

Poultry (Chicken on 

Litter) - Direct 

Applied 

0.000078

lb ai/

bird

20,000

birds 2E-07 1E-07 9E-08 2E-07 6E-08 4E-08 2E-07 6E-08 4E-08 No Data

Poultry Floor 

Management 

0.000064

lb ai/

sq ft

20,000

sq ft 1E-07 7E-08 6E-08 9E-08 4E-08 3E-08 9E-08 3E-08 2E-08 No Data

(9d) Liquid:

Backrubber 

or Facerubber

Cattle - Direct 

Applied

0.077

(lb ai/

gallon)

50 

(gallons/

day)

3E-08 5E-09 4E-09 3E-08 5E-09 3E-09 3E-08 5E-09 3E-09 No Data

0.064 2E-08 4E-09 3E-09 2E-08 4E-09 3E-09 2E-08 4E-09 3E-09 No Data

(10a) 

Wettable 

Powder: 

Backpack 

Sprayer

Beef Cattle - Direct 

Spray 0.040

400 

animals

1E-06 1E-06 9E-07 1E-06 1E-06 8E-07 1E-06 1E-06 8E-07 No Data

Swine - Direct 

Spray 0.020 7E-07 7E-07 5E-07 6E-07 6E-07 4E-07 6E-07 6E-07 4E-07 No Data

Poultry (Floor 

Management Litter, 

Fowl Tick), Poultry 

Droppings, Manure 

Piles, Garbage Piles, 

Under Feed Troughs 

0.00080 20,000

sq ft 1E-06 1E-06 9E-07 1E-06 1E-06 8E-07 1E-06 1E-06 8E-07 No Data

Poultry (Wire 

Cages) - Direct 

Spray 

0.00040 20,000

birds 7E-07 7E-07 5E-07 6E-07 6E-07 4E-07 6E-07 6E-07 4E-07 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.00032

20,000

sq ft

6E-07 6E-07 4E-07 5E-07 5E-07 3E-07 5E-07 5E-07 3E-07 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

0.00016 3E-07 3E-07 2E-07 3E-07 3E-07 2E-07 3E-07 2E-07 2E-07 No Data
Page 130 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

other Animal 

Buildings

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.000080 1E-07 1E-07 9E-08 1E-07 1E-07 8E-08 1E-07 1E-07 8E-08 No Data

Kennels, Yards, 

Campgrounds, 

Picnic Areas, and 

Recreational Parks

0.000040

1,000

sq ft

(spot)

3E-09 3E-09 2E-09 3E-09 3E-09 2E-09 3E-09 3E-09 2E-09 No Data

(10b) 

Wettable

Powder:

ManuallyPressurized 

Handwand

Beef Cattle - Direct 

Spray 0.040

400 

animals

5E-05 4E-07 3E-07 5E-05 2E-07 2E-07 5E-05 2E-07 2E-07 No Data

Swine - Direct 

Spray 0.020 2E-05 2E-07 2E-07 2E-05 1E-07 1E-07 2E-05 1E-07 1E-07 No Data

Poultry (Floor 

Management Litter, 

Fowl Tick), Poultry 

Droppings, Manure 

Piles, Garbage Piles, 

Under Feed Troughs 

0.00080 20,000

sq ft 5E-05 4E-07 3E-07 5E-05 2E-07 2E-07 5E-05 2E-07 2E-07 No Data

Poultry (Wire 

Cages) - Direct 

Spray 

0.00040 20,000

birds 2E-05 2E-07 2E-07 2E-05 1E-07 1E-07 2E-05 1E-07 1E-07 No Data

Dairy Barns, 

Poultry Houses, 

Swine Barns, or 

other Animal 

Buildings

0.00032

20,000

sq ft

2E-05 1E-07 1E-07 2E-05 1E-07 8E-08 2E-05 9E-08 8E-08 No Data

0.00016 1E-05 7E-08 7E-08 1E-05 5E-08 4E-08 1E-05 5E-08 4E-08 No Data

0.000080 5E-06 4E-08 3E-08 5E-06 2E-08 2E-08 5E-06 2E-08 2E-08 No Data

Kennels, Yards, 

Campgrounds, 

Picnic Areas, and 

Recreational Parks

0.000040

1,000

sq ft

(spot)

1E-07 9E-10 8E-10 1E-07 6E-10 5E-10 1E-07 6E-10 5E-10 No Data

(10d and 10e) 

Wettable 

Powder: 

Handheld 

Poultry (Floor 

Management) 

0.0016

lb ai/

bird

20,000 

birds No exposure data available for these use patterns. 

0.00078 20,000
Page 131 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Fogger and 

Stationary 

Fogger

lb ai/

sq ft

sq ft

Poultry (Floor 

Management Litter) 0.00023

(10f)

Wettable 

Powder: 

Rotary Duster 

(Dust -

Plunger Data 

as Surrogate)

Poultry (Floor 

Management Litter)

0.00023

lb ai/

sq ft

20,000

sq ft 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

(10g) 

Wettable 

Powder: 

Plunger 

Duster (Dust 

Data as 

Surrogate)

Poultry (Floor 

Management) 

0.0016

lb ai/

bird

1,000 

birds 9E-06 2E-06 2E-06 8E-06 1E-06 1E-06 8E-06 1E-06 1E-06 No Data

0.00078

lb ai/

sq ft 1,000

sq ft

4E-06 1E-06 9E-07 4E-06 7E-07 6E-07 4E-06 6E-07 5E-07 No Data

Poultry (Floor 

Management Litter) 0.00023 1E-06 3E-07 3E-07 1E-06 2E-07 2E-07 1E-06 2E-07 2E-07 No Data

(11a) Dust:

Self-Treating 

Dust Bag

Cattle

0.75

lb ai/

dust bag 10 

dust bags

4E-05 1E-05 9E-06 4E-05 7E-06 6E-06 4E-05 6E-06 5E-06 No Data

0.38 2E-05 5E-06 4E-06 2E-05 3E-06 3E-06 2E-05 3E-06 3E-06 No Data

0.13 7E-06 2E-06 2E-06 7E-06 1E-06 1E-06 7E-06 1E-06 9E-07 No Data

(11b) Dust:

Shaker Can

Cattle, Swine –

Direct Applied 

0.0075

(lb ai

/animal) 400 

animals

4E-04 3E-05 2E-05 4E-04 1E-05 1E-05 4E-04 1E-05 8E-06 No Data

0.0038 2E-04 1E-05 1E-05 2E-04 7E-06 5E-06 2E-04 6E-06 4E-06 No Data

Cattle – Direct 

Applied 0.0013 7E-05 5E-06 4E-06 7E-05 2E-06 2E-06 6E-05 2E-06 1E-06 No Data

Poultry (Dust Box) 

– Direct Applied

0.00060

(lb ai/ 

bird)

1,000

birds 8E-05 5E-06 5E-06 8E-05 3E-06 2E-06 8E-05 2E-06 2E-06 No Data

Poultry (Floor 

Management)

0.00030

(lb ai/ 

sq ft)

1,000 

sq ft 4E-05 3E-06 2E-06 4E-05 1E-06 1E-06 4E-05 1E-06 8E-07 No Data
Page 132 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

Swine - Bedding 0.00020 3E-05 2E-06 2E-06 3E-05 9E-07 7E-07 3E-05 8E-07 6E-07 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 1,000birds 1E-05 9E-07 8E-07 1E-05 5E-07 3E-07 1E-05 4E-07 3E-07 No Data

(11c) Dust:

Rotary Duster

(Plunger Data 

as Surrogate)

Cattle, Swine –

Direct Applied 

0.0075

(lb ai

/animal) 400

animals

6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

0.0038 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

Cattle – Direct 

Applied 0.0013 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

Poultry (Dust Box) 

– Direct Applied

0.00060

lb ai/

bird

20,000

birds 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

Poultry (Floor 

Management) 0.00030 20,000sq ft 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 20,000birds 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

(11d) Dust:

Plunger 

Duster

Poultry (Dust Box) 

– Direct Applied

0.00060

lb ai/

bird

1,000

birds 6E-04 9E-05 7E-05 6E-04 8E-05 7E-05 6E-04 8E-05 7E-05 No Data

Poultry (Floor 

Management) 0.00030 1,000sq ft 1E-05 2E-06 1E-06 1E-05 2E-06 1E-06 1E-05 2E-06 1E-06 No Data

Poultry (Wire Cage) 

– Direct Applied 0.00010 1,000birds 3E-04 4E-05 4E-05 3E-04 4E-05 3E-05 3E-04 4E-05 3E-05 No Data

(12a) Paint: 

Brush or 

Roller

Poultry (Roost 

Paint) 

0.08 

lb ai/

gallon

2 gallons

9E-07 1E-07 1E-07 9E-07 1E-07 1E-07 9E-07 1E-07 1E-07 No Data

0.077 9E-07 1E-07 1E-07 9E-07 1E-07 1E-07 9E-07 1E-07 1E-07 No Data

0.064 7E-08 1E-08 1E-08 7E-08 1E-08 9E-09 7E-08 1E-08 9E-09 No Data

0.03 3E-07 5E-08 5E-08 3E-07 5E-08 4E-08 3E-07 4E-08 4E-08 No Data

(12b) Paint: 

Airless 

Poultry (Roost 

Paint) 

0.08 

lb ai/

gallon 2 gallons

2E-07 9E-08 8E-08 2E-07 6E-08 6E-08 2E-07 6E-08 6E-08 No Data

0.077 2E-07 8E-08 8E-08 2E-07 6E-08 6E-08 2E-07 6E-08 5E-08 No Data

0.064 2E-08 7E-09 6E-09 2E-08 5E-09 5E-09 2E-08 5E-09 4E-09 No Data
Page 133 of 152

Table K.1. TCVP Occupational Handler Cancer Risk Estimates – Private/ Farmer

Exposure 

Scenario

Crop or Target App. 

Ratea

(lb ai/

unit)

Area 

Treatedb

(units/ 

day)

Private/Farmer

SL/NoG

No R

SL/G

NoR

DL/G

No R

SL/NoG

PF5 R

SL/G

PF5 R

DL/G

PF5 R

SL/No G

PF10 R

SL.G

PF10 R

DL/G

PF10 R EC

0.03 9E-08 3E-08 3E-08 8E-08 2E-08 2E-08 8E-08 2E-08 2E-08 No Data

(13) 

Solid Feed 

Additive for 

Feed Through 

Applications 

via Cup

(Granular 

Data as 

Surrogate)

Horse Feed

0.0015

(lb ai/

animal)

500 

horses

1E-09 7E-10 7E-10 6E-10 2E-10 2E-10 6E-10 1E-10 1E-10 No Data

0.00077 6E-10 3E-10 3E-10 3E-10 9E-11 9E-11 3E-10 6E-11 6E-11 No Data

Cattle Feed

0.0022

1,000 

cows

2E-08 1E-08 1E-08 9E-09 3E-09 3E-09 8E-09 2E-09 2E-09 No Data

0.0017 1E-08 7E-09 7E-09 7E-09 2E-09 2E-09 7E-09 1E-09 1E-09 No Data
Page 134 of 152

Appendix L. Summary of TCVP Labels and Use Directions

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Feed Through (Solid Additive)

270-164

Horse Oral 

Larvicide

Cup

1,100 lb horse: 0.0015

lb ai/animal/day

(2.468% ai)

Baseline 

clothing and 

gloves

Feed to horses through top dress on 

grain or mixed with the horse’s total 

ration. 

300-500 lb horse: Feed 2/5 oz. per horse 

per day

500-700 lb horse: Feed 2/5 oz. per horse 

per day

700-900 lb horse: Feed 2/5 oz. per horse 

per day

900-1,100 lb horse: Feed 2/5 oz. per 

horse per day

For larger horses over 1,00 lbs. of body 

weight feed 1⁄4 oz. for each 250 lbs. 

270-165

1,100 lb horse: 

0.00077 

lb ai/animal/day 

(1.234% ai)

Feed the recommended dosage to each 

horse separately to make certain he 

receives the full portion. Feed to horses 

through top dress on grain or mixed 

with the horse’s total ration. 

300-500 lb horse: Feed 2/5 oz. per horse 

per day

500-700 lb horse: Feed 2/5 oz. per horse 

per day

700-900 lb horse: Feed 2/5 oz. per horse 

per day

900-1,100 lb horse: Feed 2/5 oz. per 

horse per day

For larger horses over 1,100 lbs. of 

body weight feed 1⁄4 oz. for each 250 

lbs.

7698-7

Beef Cattle 

Oral Larvicide

1,400 lb beef cow

(estimated max): 

0.0022 lb 

ai/animal/day

Mix uniformly with cattle feeds 

following standard mixing procedures. 

Common feed mixing equipment (i.e., 

vertical mixers, horizontal blenders, 

mixer/feeder truck) may be used to 

prepare formulated feeds. Can be 

offered by force-feeding or free-choice 

feeding, but not both. 

Feed 1/3 lb per 100 lbs. per month, or 

an average daily intake of 70 mg daily. 

73600-4

Cattle and 

Horse Oral 

Larvicide

0.0017 lb 

ai/animal/day 

To prepare a larvicidal ration, mix 1.5 

lbs. of product per ton of complete 

mixed ration. Full feed this larvicidal 

ration to feeder cattle weighing from 

400 – 1,400 lbs or to dairy cattle at a 

rate sustaining milk production, but not 

less than 2.6 lbs of the ration per 100 lbs 

of body weight daily. 
Page 135 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Product can also be mixed with 

concentrate feeds that will provide 792 

mg per animal per day. 

Feed Through (Liquid Additive)

6552-17

Cattle 

(concentrate 

feed)

Cup/Pour

1,700 lb cow (labeled 

max): 

0.0039 lb 

ai/animal/day 

Baseline 

clothing and 

gloves

This product can be used to prepare 

concentrate feeds that will provide 70 

mgs. of ai/ 100 lbs. body weight daily. 

Feed the appropriate concentrate 

indicated to cattle weighing between 

400 and 1,200 lbs. For large cattle 

weighing between 1,200 and 1,700 lbs, 

increase the amount of premix per ton 

of concentrate to 1.5 times that 

indicated. 

Cattle 

(complete 

ration)

1,400 lb cow

(labeled max feeder 

cow):

0.0022 lb 

ai/animal/day

This product can be used to prepare 

rations containing 26.4 mg of ai/ pound 

of complete ration. Full feed the ration 

to feeder cattle weight from 400 to 

1,400 lbs, but not less than 2.6 pounds 

of the ration per 100 lbs of body weight 

daily. 

Swine

0.00060 lb 

ai/animal/day

Mix 2.6 lbs of this product per ton of 

meal type feed and offer 4-6 lbs of feed 

per animal per day. This is equivalent to 

45.4 mg of product per lb of feed. 

Horse

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

Use this product to prepare concentrate 

feeds/topdressings that will provide 70 

mgs of ai per 100 lbs of weight daily. 

11556-

160

Cattle

1,700 lb cow (labeled 

max): 

0.0039 lb 

ai/animal/day

Baseline 

clothing and 

gloves

Roughage fed separately: This product 

is used to prepare concentrate feeds that 

will provide 70 mg ai per 100 lbs body 

weight. Feed the appropriate larvicidal 

concentrate to cattle weighing between 

400 and 1,200 lbs. For large cattle 

weighting between 1,200 and 1,700 lbs, 

increase the amount of premix per ton 

of concentrate to 1.5 times that 

indicated. 

1,400 lb cow (labeled 

max): 

0.0022 lb

ai/animal/day

No other roughage fed: Mix 1.5 lbs of 

product per ton of complete mixed 

ration containing both grain and 

roughage. Full feed this complete ration 

to feeder cattle weighing from 400 to 

1,400 lbs or to dairy cattle at a rate to 

sustain milk production, but not less 

than 2.6 lbs of the ration per 100 lbs of 

body weight daily. 

Swine 0.00060 lb 

ai/animal/day

Mix 2.6 lbs of this product per ton of 

meal type feed and offer 4 to 6 lbs of 
Page 136 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

feed per animal per day. This is 

equivalent to 45.5 mg ai per pound of 

feed. 

Horse

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

Use this product to prepare concentrate 

feeds that will provide 70 mg ai per 100 

lbs body weight daily. 

Feed Block

6552-17

Cattle and 

Horse Oral 

Larvicide

Hand 

Dispersal

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day

(0.473% ai)

Baseline 

clothing and 

gloves

Provide 1 block per 5 head of cattle or 

horses. Feed at a daily rate of 0.07 

grams of Larvicide in 0.5 ounces of 

block per 100 pounds of body weight. 

7698-17

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day

Place in dry spots near loafing and 

watering areas. Cattles (or horses) 

should consume 1.05 lbs of the product 

per 100 lbs of body weight per month. 

This will supply the recommended 

average daily intake of 70 mg per 100 

lbs of body weight. 

7698-18

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day

Cattles (or horses) should consume 0.68 

lbs of the product per 100 lbs of body 

weight per month. This will supply the

recommended average daily intake of 

70 mg per 100 lbs of body weight.

9078-12

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day 

(0.31% ai)

Feed approximately 1⁄2 lb block per 

1,000 lb animal daily. 

9374-8

1,100 lb horse 

(estimated max): 

Allow free choice for cattle and horses. 

Cattle and horses should consume an 

average of 0.8 oz of the product per 100 
Page 137 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day 

(0.30% ai)

lbs of body weight per day. This will 

supply the recommended average daily 

intake of 70 mg. 

55392-3

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day 

(0.30% ai)

Provide one block per 15-20 head of 

cattle or horses. Consumption should 

average 0.83 oz of the block per 100 

lbs. This will supply the recommended 

average daily intake of 70 kg. 

73600-1

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day 

(0.49% ai)

Feed 1 block per 5 head of cattle or 

horses. Feed blocks at the rate of 0.5 oz 

per 100 lb of bodyweight per day. This 

intake will supply 0.07 g of larvicide 

per 100 lb. of bodyweight per day. 

73600-3

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

(estimated max):

0.0022 lb 

ai/animal/day 

(0.49% ai)

Feed only as a free choice source of 

salt, other minerals or vitamins. The 

product should be fed at a level to 

provide 70 mg per 100 lb of bodyweight 

per day. 

73600-5

1,100 lb horse 

(estimated max): 

0.0017 lb 

ai/animal/day

1,400 lb cow

Feed one block per 10-15 head of cattle 

or horses. Feed blocks at the rate of 

0.88 oz. per 100 lb. of body weight per 

day. This intake will supply 0.07 g of 

Larvicide per 100 lb. of bodyweight per 

day. 
Page 138 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

73600-6

(estimated max):

0.0022 lb 

ai/animal/day 

(0.30% ai)

Feed 1 block per 5 head of cattle or 

horses. Feed blocks at the rate of 0.88 

oz. per 100 lb. of bod weight per day. 

This intake will supply 0.7 g of 

Larvicide per 100 lb. of bodyweight per 

day. 

Dust

11556-

158

Beef Cattle 

and Dairy 

Cattle

Shaker 

Can, 

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0038 lb 

ai

4 oz dust: 0.0075 lb 

ai

(3% ai)

M/L/A: 

Baseline 

clothing, 

gloves, and 

PF5 

respirator

Hand dusting: apply 2 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face. 

Also can be used after grubs have 

encysted by applying 3-4 oz. of dust 

down the backline and rubbing in. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.38 lb ai per dust bag

Loaders and 

others 

handling 

dust bags: 

Baseline 

clothing, 

gloves

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags and hang in door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. The dust bag can also 

be placed in a loafing shed, holding 

pens, feedlots, near watering holes or 

other areas where cattle gather. 

Swine

Hand, 

Power 

Duster, 

Shaker Can

4 oz dust/animal: 

0.0075 lb ai/animal

1 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

M/L/A: 

Baseline 

clothing, 

gloves, and 

PF5 

respirator

Hand dusting: apply 3-4 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. One lb. of 3% 

dust should be applied per 150 sq. ft. 

Poultry

Plunger, 

Rotary 

Type 

Duster, 

Shaker can 

Duster

0.00010 lb ai/ b nird

Wire cage housing: Apply 1 lb 

dust/300 birds with plunger or rotary 

type duster or shaker can duster. 

Plunger, 

Rotary 

Type 

Duster

0.00030 lb ai/ sq ft

Floor management litter: Apply 1 

lb/100 sq ft with plunger or rotary type 

duster. 

Or, apply 3 to 8 oz/ 100 sq ft with 

plunger or rotary type duster for 

treatment of darkling beetles. 

Plunger, 

Rotary 

Type 

Duster, 

Shaker can 

Duster

0.00060 lb ai/bird Dust box: Apply 2 lbs/100 birds
Page 139 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Paint

0.030 lb ai/ gallon

(1 gallon treats 800 sq 

ft)

Roost paint: Make a thick slurry by 

mixing 1 lb of dust with 1 pint of water. 

Apply 1 lb/100 sq ft. 

11556-

182

Beef Cattle 

and Dairy 

Cattle

Shaker can, 

Rotary 

Duster, 

Spoon

1 oz. dust: 0.0038 lb 

ai

2 oz dust: 0.0075 lb 

ai

(6% ai)

M/L/A: 

Baseline 

clothing, 

gloves, and 

PF5 

respirator

Hand dusting: apply 1 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face. 

Also can be used after grubs have 

encysted by applying 1.5-2 oz. of dust 

down the backline and rubbing in. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.75 lb ai per dust bag

Loaders and 

others 

handling 

dust bags: 

Baseline 

clothing, 

gloves

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags and hang in door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. The dust bag can also 

be placed in a loafing shed, holding 

pens, feedlots, near watering holes or 

other areas where cattle gather. 

Swine

Hand, 

Power 

Duster, 

Shaker Can

2 oz dust/animal: 

0.0075 lb ai/animal

0.5 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

M/L/A: 

Baseline 

clothing, 

gloves, and 

PF5 

respirator

Hand dusting: apply 1.5-2 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. One half lb. of 

6% dust should be applied per 150 sq. 

ft. 

Poultry

Plunger, 

Rotary 

Type 

Duster, 

Shaker Can 

Duster

0.00010 lb ai/ bird

Wire cage housing: Apply 1 lb 

dust/600 birds with plunger or rotary 

type duster or shaker can duster. 

Plunger, 

Rotary 

Type 

Duster

0.00030 lb ai/ sq ft

Floor management litter: Apply 0.5 

lb/100 sq ft with plunger or rotary type 

duster. 

Or, apply 1.5 to 4 oz/ 100 sq ft with 

plunger or rotary type duster for 

treatment of darkling beetles. 

Plunger, 

Rotary 

Type 

Duster, 

Shaker Can 

Duster

0.00060 lb ai/bird Dust box: Apply 1 lbs/100 birds

Paint 0.030 lb ai/ gallon Roost paint: Make a thick slurry by mixing 1 lb of dust with 1 pint of water. 

Apply 0.5 lb/100 sq ft. 
Page 140 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

(1 gallon treats 800 sq 

ft)

19713-

340

Beef Cattle 

and Dairy 

Cattle

Shaker can,

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0038 lb 

ai

4 oz dust: 0.0075 lb 

ai

(3% ai)

Baseline 

clothing and 

gloves

Hand dusting: apply approximately 2 

oz. of dust by shaker can, rotary duster 

or by spoon to the upper portions of the 

back, neck and poll, and to the face. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.38 lb ai per dust bag

Self-treating dust bag: put dust in a 

cotton cloth or durable bag or use prepacked weather proof cattle dust bags 

and hang in barn door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. 

Swine

Hand, 

Power 

Duster, 

Shaker Can

2 oz dust/animal: 

0.0038 lb ai/animal

1 lb. per 150 sq. ft:

0.00020 lb/ sq ft

Hand dusting: apply 1.5-2 oz of dust by 

conventional hand or power duster to 

each animal with special attention given 

to the neck and around the ears. 

One lb of 3% dust should be applied per 

150 sq ft of bedding.

47000-

113

Beef Cattle 

and Dairy 

Cattle

Shaker can, 

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0038 lb 

ai

4 oz dust: 0.0075 lb 

ai

(3% ai)

Baseline 

clothing and 

gloves

Hand dusting: apply 2 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face. 

Also can be used after grubs have 

encysted by applying 3-4 oz. of dust 

down the backline and rubbing in. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.38 lb ai per dust bag

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags and hang in door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. The dust bag can also 

be placed in a loafing shed, holding 

pens, feedlots, near watering holes or 

other areas where cattle gather. 

Swine

Hand, 

Power 

Duster, 

Shaker Can

4 oz dust/animal: 

0.0075 lb ai/animal

1 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

Hand dusting: apply 3-4 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. One lb. of 3% 

dust should be applied per 150 sq. ft. 

Poultry

Plunger, 

Rotary 

Type 

0.00010 lb ai/ bird

Wire cage housing: Apply 1 lb 

dust/300 birds with plunger or rotary 

type duster or shaker can duster. 
Page 141 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Duster, 

Shaker Can 

Plunger, 

Rotary 

Type 

Duster

0.00030 lb ai/ sq ft

Floor management litter: Apply 1 

lb/100 sq ft with plunger or rotary type 

duster. 

Or, apply 3 to 8 oz/ 100 sq ft with 

plunger or rotary type duster for 

treatment of darkling beetles. 

Plunger, 

Rotary 

Type 

Duster, 

Shaker Can 

Duster

0.00060 lb ai/bird Dust box: Apply 2 lbs/100 birds

Paint

0.030 lb ai/ gallon

(1 gallon treats 800 sq 

ft)

Roost paint: Make a thick slurry by 

mixing 1 lb of dust with 1 pint of water. 

Apply 1 lb/100 sq ft. 

47000-

122

Beef Cattle 

and Dairy 

Cattle

Shaker 

Can, 

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0038 lb 

ai

(3% ai)

Baseline 

clothing and 

gloves

Hand dusting: apply 2 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.38 lb ai per dust bag

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags and hang in door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. The dust bag can also 

be placed in a loafing shed, holding 

pens, feedlots, near watering holes or 

other areas where cattle gather.

Swine

Hand, 

Power 

Duster, 

Shaker Can

4 oz dust/animal: 

0.0075 lb ai/animal

1 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

Hand dusting: apply 3-4 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. One lb. of 3% 

dust should be applied per 150 sq. ft.

47000-

123

Beef Cattle 

and Dairy 

Cattle

Shaker 

Can, 

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0013 lb 

ai

(1% ai) Baseline 

clothing, 

coveralls, 

gloves and 

dust mist 

respriator

Hand dusting: apply 2 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face. 

Hand Pour

12.5 lbs (estimated 

max dust bag):

0.13 lb ai per dust bag

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags. Suspend bags in gateways or lanes 

through which the animals pass daily 

for water, feed or minerals. The dust 
Page 142 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

bag can also be placed in a loafing shed, 

holding pens, feedlots, near watering 

holes or other areas where cattle gather.

Hand, 

Power 

Duster

12 oz dust/animal: 

0.0075 lb ai/animal

3 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

Hand dusting: apply 9-12 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. Three lbs of 

1% dust should be applied per 150 sq. 

ft.

Horse Hand, 

Shaker Can

6 oz. dust/animal: 

0.0038 lb ai/animal

No application rate 

defined for premise 

dusting.*

Apply 6 oz by shaker can, hand duster, 

grooming brush or dust mitt. Cover 

upper portions of the back, neck and to 

the face, mane and tail for added control 

of face flies. 

For premise dusting, apply to barn or 

stall area floors where manure 

accumulates.*

Dogs

(Kennels)

Plunger 

Duster, 

Shaker Can

No application rate 

defined.* 

Occasional dusting in and around 

sleeping quarters and other areas will 

help free area of ticks and fleas. Dust 

bedding as well.*

47000-

125

Beef Cattle 

and Dairy 

Cattle

Shaker 

Can, 

Rotary 

Duster, 

Spoon

2 oz. dust: 0.0038 lb 

ai

(3% ai)

Baseline 

clothing and 

gloves 

Hand dusting: apply 2 oz. of dust by 

shaker can, rotary duster or by spoon to 

the upper portions of the back, neck and 

poll, and to the face.

Hand, Pour

12.5 lbs (estimated 

max dust bag):

0.38 lb ai per dust bag

Self-treating dust bag: put dust in a 

cotton cloth or double burlap bag or use 

prepacked weather proof cattle dust 

bags and hang in door exits or 

alleyways leading from animal 

buildings, salt or mineral blocks or 

watering holes. The dust bag can also 

be placed in a loafing shed, holding 

pens, feedlots, near watering holes or 

other areas where cattle gather.

Swine

Hand, 

Power 

Duster, 

Shaker Can

4 oz dust/animal: 

0.0075 lb ai/animal

1 lb. per 150 sq. ft:

0.00020 lb/ sq ft.

Hand dusting: apply 3-4 oz of dust by 

hand or power duster to each animal. 

In severe infestations, both animals and 

bedding may be treated. One lb. of 3% 

dust should be applied per 150 sq. ft.

Poultry

Plunger, 

Rotary 

Type 

Duster, 

Shaker can 

Duster

0.00010 lb ai/ bird

Wire cage housing: Apply 1 lb 

dust/300 birds with plunger or rotary 

type duster or shaker can duster. 
Page 143 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Plunger, 

Rotary 

Type 

Duster

0.00030 lb ai/ sq ft

Floor management litter: Apply 1 

lb/100 sq ft with plunger or rotary type 

duster. 

Or, apply 3 to 8 oz/ 100 sq ft with 

plunger or rotary type duster for 

treatment of darkling beetles. 

Hand 0.00060 lb ai/bird Dust box: Apply 2 lbs/100 birds

Paint

0.030 lb ai/ gallon

(1 gallon treats 800 sq 

ft)

Roost paint: Make a thick slurry by 

mixing 1 lb of dust with 1 pint of water. 

Apply 1 lb/100 sq ft. 

Emulsifiable Concentrate Spray

11556-

162

Beef Cattle 

Spray

0.026 lb ai/animal

(23% ai)

Baseline 

clothing, 

coveralls, 

and gloves

Dilute 1 gallon of product in 75 gallons 

of water. Use between 0.5 and 1 gallon 

of diluted spray solution per animal. 

0.039 lb ai/animal

For severe tick infestations, dilution 

may be increased to 1 gallon in 50 

gallons water. 

Lactating 

Dairy Cattle 0.0049 lb ai/animal

Dilute 1 gallon of product in 200 

gallons of water. Direct spray to cover 

thoroughly with up to 0.5 gallon of the 

dilution per animal. 

Beef and 

Dairy Cattle

Backrubber 

or 

Facerubber

0.077 lb/gallon

Dilute 1 gallon of product in 25 gallons 

water. Pour diluted solution into oil 

reservoir of mechanical rubbing devices 

or pour 1 gallon per 20 feet on burlap or 

rope backrubbers. 

Poultry

(Caged)

Spray

0.039 lb ai/100 birds

0.00031 lb ai/bird

Dilute 1 gallon product in 50 gallons of 

water. Apply 1 gallon of dilution/100 

birds under high pressure. For 

individual bird treatment, apply 1 oz/ 

bird. 

Poultry

(Chickens on 

Litter)

0.000078 lb ai/ sq ft

Dilute 1 gallon product in 50 gallons of 

water. Apply 1-2 gallons of 

dilution/1,000 square feet evenly with 

penetration of litter surface. 

Poultry

Roost Paint 

or Spray 0.077 lb ai/ gallon

Dilute 1 gallon of product in 25 gallons 

of water. Apply 1 pint of dilution/100 ft 

of roost area with brush or spray. 

Buildings 0.00077 lb ai/ sq ft

Dilute 1 gallon of product in 25 gallons 

of water. Apply 1 gallon of 

dilution/100-150 sq ft to thoroughly 

cover walls, ceilings, floors, cracks and 

crevices using high pressure spray.

Poultry and 

Livestock 

Facilities

Spray 0.00015 lb ai/ sq ft

Residual surface spray: Dilute 1 gallon 

of product in 25 gallons of water. 

Apply 1 gallon of dilution/500-1,000 sq 
Page 144 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

ft. Extreme infestations may necessitate 

increasing the diluted spray to 1 gallon 

product per 12.5 gallon water. 

0.00077 lb ai/ sq ft

Larvicide: Dilute 1 gallon of product in 

25 gallons of water. Apply 1 gallon of 

dilution/100 sq ft. 

Kennels 0.000078 lb ai/ sq ft

Dilute 1 gallon of product in 50 gallons 

of water. Apply 1 gallon of 

dilution/500-1,000 sq ft as a spot 

treatment only once per year. 

67517-

33

Beef Cattle

Spray

0.032 lb ai/animal 

(24% ai)

Baseline, 

gloves, and 

organic 

vapor 

respirator

Dilute to a 0.30% - 0.50% solution. 

Use between 0.5 to 1 gallon of spray per 

animal. 

Lactating 

Dairy Cattle 0.0013 lb ai/ animal Dilute to a 0.040% solution. Use 0.50 gallon of spray per animal. 

Beef and 

Lactating 

Dairy Cattle

Backrubber 0.064 lb ai/gallon

Baseline, 

gloves, 

coveralls, 

and organic 

vapor 

respirator

Dilute to a 1.0% solution. Mix with #2 

diesel oil or any approved backrubber 

base oil. 

Swine

Spray, 

High 

Pressure 

Sprayer

0.016 lb ai/animal

Baseline, 

gloves, and 

organic 

vapor 

respirator

Dilute to a 0.5% solution. Apply a 

coarse spray using 0.25 to 0.5 gallon per 

head to thoroughly wet the animal. 

Poultry (Wire 

Cage)

0.032 lb ai/100 birds 

(gallon)

0.00025 lb ai/bird

Dilute to a 0.5% solution. Apply 1 

gallon/100 birds directly to birds, spray 

vent and fluff areas from below. For 

individual bird treatment, apply 1 oz of 

mixture per bird. 

Poultry (Floor 

Management)

0.000064 lb ai/ sq ft 

(2 gallons)

Dilute to 0.5% solution. Apply 1-2 

gallons/1,000 sq ft evenly for 

penetration to litter surface. 

Poultry (Roost 

Paint) Paint 0.064 lb ai/ gallon

Dilute to 1.0% solution. Apply 1 pint 

solution/100 sq ft. Treat with a brush or 

spray thoroughly. 

Poultry

(Fowl Tick)

Power 

Sprayer 0.00064 lb ai/ sq ft

Dilute to 1.0% solution. Apply 1 gallon 

solution/100-150 sq ft to walls, ceiling, 

floors, cracks and crevices with a power 

sprayer. 

Poultry

(Flies 

Residual)

Spray

0.00013 lb ai/ sq ft

Dilute to 1.0% solution. Apply 1 

gallon/500-1,000 sq ft thoroughly to 

point of runoff to walls, ceilings, and 

where flies congregate and feed. 

Poultry 

(Larvicide) 0.00064 lb ai/ sq ft Dilute to 1.0% solution. Apply 1 gallon solution/100 sq ft of droppings. 

Woody 

Borders of 

Kennels, 

Yards, 

Campgrounds, 

Recreational 

0.032 lb ai/ sq ft Dilute to 0.5% solution. Apply as a 

spot spray.
Page 145 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

Parks, 

Footpaths and 

Roadways

Wettable Powder

11556-

156

Beef Cattle

Spray

0.040 lb ai/animal

(1 gallon)

MLA for 

dusting, low 

pressure 

handwand 

and paint 

applications:

Baseline 

clothing, 

gloves, 

coveralls, 

dust mist 

respirator

All other 

MLA and 

other 

handlers:

Baseline 

clothing and 

gloves

Dilute to a 0.35-0.50% solution. Use a 

low pressure coarse spray and apply to 

point before runoff. Use between 0.5 to 

1 gallon of spray solution per animal. 

Swine

0.020 lb ai/animal

(0.5 gallon)

Dilute to a 0.50% solution. Apply as a 

low pressure coarse spray and apply 

only to point before runoff. Use 0.25 to 

0.50 gallon maximum solution per head 

to treat. 

Poultry

(Wire Cages)

0.00040 lb ai/ bird

(gallon)

0.00031 lb ai/bird

(1 oz)

Dilute to a 0.50% solution. Apply 

directly to birds (1 gallon solution/100 

birds). For individual bird treatment 

apply 1 oz of the mixture per bird. Use 

power sprayer.

Poultry (Floor 

Management 

Dusting)

Handheld 

Fogger, 

Plunger 

Duster, 

Stationary 

Fogger

0.0016 lb ai/ bird Apply 2.5 oz wettable powder/50 birds. 

Poultry (Floor 

Management 

Roost Paint)

Paint

0.080 lb ai/ gallon

(1 gallon treats 800 sq 

ft)

Dilute to a 1.0% solution. Treat with 

brush or spray thoroughly using 1 

pint/100 ft. 

Poultry (Floor 

Management 

Litter)

Spray 0.00080 lb ai/ sq ft

(2 gallons)

Dilute to a 0.50% solution. Apply 1-2 

gallons solution/100 sq ft for 

penetration of litter surface. 

Handheld 

Fogger, 

Rotary 

Duster, 

Stationary 

Fogger

0.00023 lb ai/ sq ft

(0.75 oz)

Treat evenly using 0.75 oz wettable 

powder/100 sq ft. Use rotary, 

mechanical or electrostatic duster. 

Poultry (Fowl 

Tick)

Spray

0.00080 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. Apply 1 

gallon solution/100-150 sq ft to walls, 

ceiling, floor cracks, and crevices with 

power sprayer. 

Dairy Barns, 

Poultry 

Houses, 

Swine Barns, 

or other 

Animal 

Buildings

0.00032 lb ai/ sq ft

(1 gallon)

Dilute to a 2.0% solution. For dry 

whitewashed wood or concrete block 

surfaces use 1 gallon of solution/500 sq 

ft. 

0.00016 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. For 

unpainted wood or painted concrete 

block surfaces, use 1 gallon of 

solution/500 sq ft. 
Page 146 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

0.000080 lb ai/ sq ft

(0.5 gallon)

Dilute to a 1.0% solution. For Masonite 

or galvanized sheet metal surfaces, use 

0.5 gallon of solution/ 500 sq ft. 

Poultry 

Droppings, 

Manure Piles, 

Garbage Piles, 

Under Feed 

Troughs

0.0008 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. Apply 1 

gallon of solution/100 sq ft. 

Kennels, 

Yards, 

Campgrounds, 

Picnic Areas, 

and 

Recreational 

Parks

0.000040 lb ai/ sq ft

(spot)

Dilute to a 0.5% solution. Apply as a 

spot treatment using a low pressure 

handwand sprayer only. Apply woody 

borders. 

47000-

126

Beef Cattle

Spray

0.040 lb ai/gallon

MLA for 

dusting and 

paint 

applications:

Baseline 

clothing, 

gloves, 

coveralls, 

dust mist 

respirator

All other 

MLA: 

Baseline 

clothing, 

gloves

Dilute to a 0.35-0.50% solution. Use a 

low pressure coarse spray and apply to 

point before runoff. Use between 0.5 to 

1 gallon of spray solution per animal.

Swine 0.020 lb ai/animal

(0.5 gallon)

Dilute to a 0.50% solution. Apply as a 

coarse spray. Use 0.25 to 0.50 gallon 

maximum solution per head to treat. 

Poultry

(Wire Cages)

0.00040 lb ai/ bird

(gallon)

0.00031 lb ai/bird

(1 oz)

Dilute to a 0.50% solution. Apply 

directly to birds (1 gallon solution/100 

birds). For individual bird treatment 

apply 1 oz of the mixture per bird. Use 

power sprayer.

Poultry (Floor 

Management 

– Litter)

Handheld 

Fogger, 

Plunger 

Duster, 

Stationary 

Fogger

0.00078 lb ai/ sq ft Treat evenly and thoroughly using 2.5 

oz/100 sq ft. 

Poultry (Floor 

Management -

Dusting)

0.0016 lb ai/ bird Apply 2.5 oz wettable powder/50 birds. 

Poultry (Floor 

Management 

Roost Paint)

Paint

0.080 lb ai/ gallon

(1 gallon treats 800 sq 

ft)

Dilute to a 1.0% solution. Treat with 

brush or spray thoroughly using 1 

pint/100 ft. 

Poultry (Fowl 

Tick)

Spray**

0.00080 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. Apply 1 

gallon solution/100-150 sq ft to walls, 

ceiling, floor cracks, and crevices with 

power sprayer. 

Dairy Barns, 

Poultry 

Houses, 

Swine Barns, 

or other 

Animal 

Buildings

0.00032 lb ai/ sq ft

(1 gallon)

Dilute to a 2.0% solution. For dry 

whitewashed wood or concrete block 

surfaces use 1 gallon of solution/500 sq 

ft. 

0.00016 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. For 

unpainted wood or painted concrete 

block surfaces, use 1 gallon of 

solution/500 sq ft. 
Page 147 of 152

Table L.1. Summary of TCVP Occupational Livestock Use

EPA 

Reg. No. Use Site

Applic. 

Type/ 

Equipment

Applic. Rate 

(lb ai/A) PPE Use Directions and Limitations

0.000080 lb ai/ sq ft

(0.5 gallon)

Dilute to a 1.0% solution. For Masonite 

or galvanized sheet metal surfaces, use 

0.5 gallon of solution/ 500 sq ft. 

Poultry 

Droppings, 

Manure Piles, 

Garbage Piles, 

Under Feed 

Troughs

0.000080 lb ai/ sq ft

(1 gallon)

Dilute to a 1.0% solution. Apply 1 

gallon of solution/100 sq ft. 

Table L.2. Summary of TCVP Occupational 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 148 of 152

Table L.2. Summary of TCVP Occupational 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. 

Do not reapply product for 30 days. 

*PPE: Baseline clothing, coveralls, gloves and dust mist respirator.

Dogs

Estimated Range: 

170 mg ai, small

430 mg ai, medium
Page 149 of 152

Table L.2. Summary of TCVP Occupational 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. 
Page 150 of 152

Appendix M. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and 

Human-Equivalent Doses 

The calculation of HECs accounts for pharmacokinetic (not pharmacodynamic) interspecies 

differences. HECs for residential and occupational scenarios were derived using the POD from 

the route-specific inhalation study and the regional deposited-dose ratio (RDDR). The RDDR 

accounts for the particulate diameter [mass median aerodynamic diameter (MMAD) and 

geometric standard deviation (GSD)] and estimates the different dose fractions deposited along 

the respiratory tract. Table M.1 summarizes the inputs used to obtain the TCVP RDDR for HEC 

calculations.

Table M.1. Summary of RDDR Inputs for TCVP

Study 

MRID

Species 

and 

Strain 

Animal 

Body 

Weight 

(g)1

Duration of Exposure

BMDL 

(mg/L)

BMD 

(mg/L)

MMAD 

(μm)3

GSD 

(μm)3

Respiratory 

Region for 

Effect4

RDDR

hours/day days/week2

48803501

Sprague 

Dawley 

Rats

267 6 5.5 0.022 0.12 2.57 3.785 ER 2.525

NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. MMAD = mass median aerodynamic diameter. 

GSD = geometric standard deviation. RDDR = regional deposited-dose ratio.

1 Default Sprague Dawley rat body weight for males (sensitive sex).

2 Rats were exposed 5 days a week for 3 weeks and 7 days a week for the last week resulting in an average of 5.5 days/week.

3 MMAD and GSD selected from the dose closest to the BMD and BMDL values (0.05 mg/L).

4 ET = extrathoracic, TB = tracheobronchial, PU = pulmonary, TH = thoracic, TR = total respiratory tract, ER = extrarespiratory (systemic). 

The POD from the route-specific inhalation study was adjusted for expected human exposure 

duration. Duration adjustment is performed based on Haber’s law, which assumes that a 

toxicological effect is proportional to the product of exposure level and duration. Animal-tohuman ratios of daily (hours/day) and weekly (days/week) exposures are applied to the animal 

inhalation study POD to result in a duration-adjusted animal POD for HEC conversion. For 

example, expected human exposure for occupational exposures is 8 hours/day and 5 days/week. 

Therefore, the adjusted POD is 0.0165 mg/L.

PODadjusted =

0.02 mg

L

×

6 hr/day

8 hr/day ×

5.5 days/week

5 days/week =

0.0165 mg

L

For residential handler and outdoor post-application exposures, no duration adjustment was 

applied. For residential indoor post-application exposures, a duration adjustment to 7 days/week 

was applied with no daily exposure adjustment resulting in a duration-adjusted POD of 0.0157 

mg/L. For residential bystander exposures, duration adjustments to 24 hours/day and 7 

days/week were applied resulting in a duration-adjusted POD of 0.0039 mg/L. 

The RDDR was applied to the duration-adjusted POD (except residential handler and outdoor 

post-application exposures with no duration adjustment where the RDDR is applied directly to 

the POD) to calculate HECs (presented in Table M.3 below). 

HEC = PODadjusted × RDDR
Page 151 of 152

Human-equivalent doses were subsequently calculated from the HECs for residential and 

occupational handler scenarios. The following equation describes the conversion from HECs to 

human-equivalent doses:

The conversion to human-equivalent doses is an approximation involving the application of a 

conversion factor (CF) that takes into account the typical human volume respired per unit time. 

As the default breathing rate in the HEC calculation is 13.8 L/min for a typical human (body 

weight of 70 kg) under light activity conditions, the corresponding CF is 11.8 L/hr-kg. 

Absorption differences through the respiratory tract as compared to the oral route are expressed 

in the ratio “A.” In current practice, HED customarily assumes “A” to be unity (i.e., the entire 

animal orally administered dose is assumed to be absorbed via the inhalation route). Because the 

inhaled dose depends on activity level which directly impacts breathing parameters (at least until 

blood steady state levels are reached), the activity factor (AF) is a relative ratio that attempts to 

account for differences in respiratory rate due to activity level. Table M.2 lists the different 

exposure scenarios, the corresponding breathing rates associated with these activities, and the AF 

values that should be used for different occupational handler scenarios being assessed. Also 

listed in Table M.2 is the AF value assigned to residential handlers, which is assumed to be equal 

to occupational handlers in non-agricultural settings. The daily exposure duration (D) is 

equivalent to the “hours/day” value used in POD duration adjustment calculations. A summary 

of duration adjustments, HECs, and human-equivalent doses for all potential occupational and 

residential scenarios is presented in Table M.3. 

1 AF = Exposure scenario-specific human breathing rate (L/min) ÷ 13.8 L/min (the rate assumed in HEC calculation). Body 

weight is assumed to be 70 kg for all calculations.

Table M.2. Assigned Activity Factor (AF) Values Based on Different Handler Exposure Scenarios

Exposure Scenario Human Breathing Rate

(L/min)

HED Calculation Inputs

AF1

Occupational

Pilots, tractor drivers 

(groundboom, airblast) 8.3 0.6

Mixer/loaders, lawn care 

operators (non-agriculture) 16.7 1.2

Handheld spray applications 

(e.g., backpacks, handgun, etc.) 29 2.1

Residential Handlers 16.7 1.2

Human-Equivalent Dose ≈ HEC (mg/L) × CF (L/hr-kg BW) × A × AF × D (hr/day)

HED = Human-Equivalent Dose (mg/kg BW/day).

HEC = Human-Equivalent Concentration (mg/L).

CF = Human-specific value that accounts for volume respired per unit time. CF equals 11.8 L/hr-kg based on the 

default-breathing rate assumed for a typical human (body weight of 70 kg) in the HEC calculation.

A = Absorption ratio through the respiratory tract as compared to the oral route – assumed to be unity. 

AF = Relative ratio that accounts for relative changes in respiratory rate due to activity level. Different AF values 

should be used for different occupational and residential scenarios.

D = Duration of daily exposure in hours: 8 hours assumed for occupational exposures; 24 hours assumed for 

bystanders/residential exposure; and 2 hours is often assumed for residential handler exposures.
Page 152 of 152

Table M.3. Summary of Inhalation Calculations for Human-Equivalent Concentrations and Doses for TCVP

Population Scenario

Toxicity Duration 

Adjustment

Human-Equivalent 

Concentration

Human-Equivalent Dose

(mg/kg/day; breathing rate specific)

hours/day days/week mg/L mg/m3 8.3 L/min 16.7 L/min 29 L/min

Occupational Handler 8 5 0.04166 41.66 2.371 4.771 8.285

Residential

Handler NA NA 0.05555 55.55 NA 1.590 NA

Outdoor postapplication NA NA 0.05050 50.50 NA NA NA

Indoor postapplication NA 7 0.03968 39.68 NA

Bystander 24 7 0.00992 9.92 NA

NA = not applicable (the expected duration of the exposure scenario is less than the duration of available inhalation toxicity 

studies; downward adjustments are not permitted). Note: for all exposure scenarios, the rounded value of 0.02 mg/L was used as 

the POD, except residential handler which used the unrounded value of 0.022 mg/L.