### UNITED STA TES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D .C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

### MEMORAND UM

Date: December 2I,2015

SU BJE C T : Tetrach l orvinphos ( T CVP) Human Health Draft Risk Assessment 

### ( ORA) for Regi strat ion Review

PC Code: 083 70 I

, 

### 083 702
P e tition No .: NA
Ri s k Assessment T y p e: Single Chemical Aggregate
TXRNo.: NA
M RIDNo.: NA DP Barcode: D4 l l 095 Registrat i on Nos

. : NA Regu l atory Action: Registration
Review
Case No.: 1321
CAS No.: 22248-79-9 40 CFR: 

### § 180

. 252

F RO M: Dan ette Drew

, Chemist/Risk**Assesso~~~~-A .....---**  

### Linda Taylor

, Ph.D. Toxicologi**~** 

### Risk Assessment Branch 

### V N I
Health Effects Division (HE D

, 7509P) And
Wade Britton

, MPH, Envi ronm ental Health Scient i st Risk Assessment Branch 

### IV
Health Effects Di v ision ( HED

, 7509P) .·

THR OU GH: Michael Metzger, Branch Ch ief

# ~**f~y** 

# .(). /**4~** Risk Assessment Branch 

# v NII \ l 

# y 

# I/ 

# r

And

TO: Health Effec t s Di v ision ( H ED, 7509P)

HED RARC (Risk Assessment R eview**~°1m~e~~ewers:** 

### Michael A. 

### Doherty

, Ph .D., Chemist**~~** 

### ,, Monique M. Perron, Sc.D.

, Toxicolo g ist

# ~ 

# ./_.tNV--

Health Effects Divis i on (HE D, 7509P)

Jam es Parker

, Che mical Review Manager
Thomas Moriarty

, RMS I Risk Management and Imp l ementatio n Bran ch I Pesticide Re- eval uation Di v i sio n ( 7508P)

Attached i s HED's human health risk assessment in support of the registrat i on re view of the
in sec ticide t e trachlorvinphos.

### 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 Anima l 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 Charact erization

................................ ................................ ... 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 Human

Equivalent Doses

................................ ................................ ................................ ........................ 150

### Page 4 of 152

1.0 Executive Summary

The insecticide t etrachlorvinphos (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), emuls ifiable concentrates (EC), feed through (solid and liquid food additives), feed blocks, and wettable powders (WP). Human e xposure to TCVP in food may occur as a result of consuming residues in animal commodities

. Exposure may also occur from drinking wat er 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 l ivestock 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 a ssessment 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 (9 th 

### 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 TCV P pet products. ( The EPA point

- by

- point response to NRDC comments can be found in D430589 2 

### .) The current TCVP human health risk assessment reflects the following changes since the 2014 residential assessment:

 In clusion of the 10X FQPA safety factor /uncer tainty 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 th at 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 res idue transfer studies (an amitraz pet collar study 3 

### (herein referred to as “the amitraz study”) and a literature study using TCVP pet collars (Davis, 2008 4



### , herein r eferred 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 (9 th Cir.)

3 MRID 49468801: Determination of Tr ansferable 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 a t 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 assessment s

. The steady state point of departure is protective of any exposure duration longer th an 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 lif

estages, 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 endp oint 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 ( p ostnatal day; PND11) components of the comparative cholinesterase assay ( CCA ) study

. I n 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 b oth 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. Furtherm ore, 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/carcino ma 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 exp osure 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, you ths 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 300 X is appropriate for all inhalation exposures (3X for interspecies extrapolation, 10X for intraspecies variation, and a 10X FQPA SF for resid ential assessm ents 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 di scussed 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.
T he differences in U.S. and Canadian residue defin itions 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 ) exp osure 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 Analys is Division (BEAD) of OPP provided percent livestock treated information. Model

- derived estimated drinking water concentrations (EDWCs) were provided by the E nvironmental Fate and Effect Division (EFED). For acute and cancer dietary analyses, the EDWCs we re 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 residentia l 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 4 3 % 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/po wders, 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 co ntact previously treated pets. The lifestages selected for each residential scenar io [ 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 inhalati on) for TCVP dusts/powders range from 10

- 8 

### to 10

- 7 

### , and for pump/trigger sprays range from 10

- 9 

### to 10

- 8



### .

Pet Collars: All residential handler (adults) non

- cancer (steady state) inhalation risks estimated for the TCVP pet collars (whether assessed as l iquid 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 i n the 10

- 7 

### range when assuming a dust formulation.

Post

- App lication 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 or al) 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 conce rn 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

- 7 

### to 10

- 6 

### and, 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 amit raz 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: P ost

- 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 post

application child non

- cancer incidental oral risk is of concern (MOE = 650; LOC=1000)

. Estimated adult post

- application cancer risks range from 10

- 6 

### to 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 ). A ll estimated adult post

application canc er 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 stud y was greater than that in the amitraz study; therefore , post

- application exposures from TCVP pet collars would be grea ter, 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 acut e aggregate risk assessment includes only dietary (food and drinking water) exposures. There are no acute aggr egate risk estimates of concern.

Stea d y 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 post

application activities (contacting treated pets). All p et collar produc ts were assessed as both a liquid formulation and as a solid (dust) formulation

.

Handler: Residential handler (adult) steady state aggregate (food, water, residential) r isk estimates for all TCVP pet product scenarios (collars, dust/powders, a nd pump/trigger sprays) are not of concern ( Aggregate Risk Index (ARI) ≥ 1 )

.

Post

- application: For the TCVP dust/powder pet products, the steady state post

application aggregate assessments result in 16 of the 17 scenarios with risk estimates of concern (M OEs < 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 s cenarios 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. Assumi ng collars are solid (dust) formulation s and using the amitraz study, all 23 scenarios resulted in aggregate MOEs of concern. Quantitative a ssessments 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. F or 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

formu lation

.

Handler: For the handler cancer aggregate, a ll registered pet product scenarios (collars, dust/powders, a nd pump/trigger sprays) result in residential handler cancer aggregate (residential and dietary) risk estimates in the 10

- 6 

### range.

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

- 6 

### range. A ssuming liquid formulation of pet collars, aggregate risk estimates are in the 10

- 6 

### range using the amitraz study and are in the 10

- 5 

### to 10

- 6 

### range 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 

### r ange (cancer aggregate risk estimate values would be lower if using the Davis data ).

Occupational Risk Assessment

N on

- cancer (steady state) and cancer exposures and risks were calculated for occupational handlers of TCVP for all registered uses

. G eneric , 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.

S teady state inhalation exposure and risk estimates were calculated for occupationa l handlers of TCVP for a variety of exposure scenarios at differing levels of respiratory personal protection i ncluding engineering controls. Steady state d ermal 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 2 0 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

- 5 

### for private/farmer handlers and from 10

- 10 

### to 10

- 4 

### for contract/commercial handlers with currently required PPE.

Occupational post

- application exposures ar e not expected as reentry activities are not ant icipated 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 chemic al. These data, which include studies from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) database; the ARTF database; the Resi dential 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 (MR ID 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 Boa rd (HSRB)

. Descriptions of data sources, as well as guidance on their use, can be foun d at the a gency website 5



### .
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) f or the determination of tetrachlorvinphos and its metabolites (TCVPdeme, TCPEdiol, TCPEone and TCPEol) in livestock commodities

, which uses QuEChERS and LC/MS/MS methods. T he 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, t he metabolites TC PEol and TCPEone were recoverable under Protocol F, although f

ortified 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) es tablished 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. T he differences in U.S. and Canadian residue definitions

pro hibit harmonization . H ED 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 meta bolites, 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 o n 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. Kniz ner).

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

Toleran ce 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

Toleran ce 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
T CPEdiol (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

grea ter 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 15 2

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. 6 1483

- 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 al low 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 In troduction

3.1 Chemical Identity

T able 3.1

. Tetrachlorvinphos Nomenclature.
Compound

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 9 3

- 98 ° C

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

- 7 

### torr (25°C )

. The solubility of tetrachlorvinphos in water at 25°C is 11.6 mg/L . T CVP has limited solubilit y in most aromatic hydrocarbons. TCVP is hydrophobic, with an octanol

- water partition coefficient of 3350 (Log K ow 

### 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 p erimeter 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), emulsifi able 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; manuall y

- 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 o f registered use s, 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 (handle r and post

application) 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 ant icipated 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

- e stablished 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 w arrant. 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 conside rations 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 specif

ic 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 acti ve 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 datab ase 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) cholin esterase (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 st udy 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 evi dence 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 absorptio n 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 Ef

fects

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 incl uding 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 in hibition 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 describ ed 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 shoul d 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 m ore 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 adul t 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, n ose, 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 cholinesteras e 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 dosi ng 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 pr otective 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. Development al 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 mate rnal 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 ad ult 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 linea r 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 BMD 10 

### 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 BMD 10 1



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

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

### )

MRID 45570601 (21

- day oral) 21 days 10% at 9.9 (BMD 10 

### )

MRID 43371201 (90

- day oral) 90 days 10% at 10.5 (BMD 10 

### )

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 (BMD 10 

### )

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

### )

MRID 45570601 (21

- day oral) 21 days 10% at 14.7 (BMD 10 

### )

MRID 43371201 (90

- day oral) 90 days 12% at 6.7

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

1 The 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,

w hich 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 administ ered 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 BMD 10 

### /BMDL 10 

### values from 6.8 to 61.6 mg/kg/day BMD 10 

### / 3.6 to 26.3 mg/kg/day BMDL 10 

### (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 r at 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% increas ed 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 acut e 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 A ChE 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, non

pregnant female rats showed approximately 40% RBC AC hE 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 BMDL 10 

### 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 7 5 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. N o 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 t he 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 durati on 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 L iterature Review on Neurodevelopment Effects

For the OPs, historically the a gency 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 show s 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 f or 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., 12/2 9/2014) 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 r aised 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, t he 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, 2013 6 

### ) and concludes they a re 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.reg ulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2008

- 0850

- 0170

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neurodevelo pmental 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, 2 013; 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 dime thyl 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 a re 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, s pecific 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_organophosph orus_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
Tetrachlorvi n phos 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., Fortenberr y 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 tri clopyr; 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 CHAR GE 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 DAP s 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 wi th 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

asses sed 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 r eported 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 e t 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 a l. (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 tot al 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 Bou chard, 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 (2 013) 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 sugges tive 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

ex posure, 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 r eciprocal 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 ass ociations 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 re ported 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 i nfant 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 observe d. 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% c hlorpyrifos 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 R BC AChE inhibition.

A review of the scientific literature on potential modes of action/adverse outcome pathways (MOA/AOP) 8 

### leading to effects on the developing brain was conducted for the 2012 FIFRA SAP meeting (USEPA, 2012) and updated for the December 2 014 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 n on

- 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 extrapolati on, 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 submitt ed 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 o ften 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 o f 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. T hese 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 associati ons 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 e arly 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 insta nces), 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 a nd 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 chil dren.” 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 suscep tibility 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 q uantitat ive 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, quantitativ e 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 r espect 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. E pidemiology 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 in telligence 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 stu dy 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 f or 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

q uantitative 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 th e 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 F actor 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 assessme nts use data from surrogate and chemical

specific 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 endpo ints 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
A ppendix A ). However, based upon the robustness of the ACh E 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 m ore 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 life stage 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 compon ent 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 BMDL 10 

### 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 durati on 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 sign ificantly 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 BMDL 10 

### 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 durati ons 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 de parture 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 BMD 10 

### s and BMDL 10 

### s. The
BMD 10 

### is the estimated dose where AChE is inhibited by 10% compared to background A ChE activity. The BMDL 10 

### is the lower confidence bound on the BMD 10 

### value. As a matter of science policy, the a gency 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/k g (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 BMDL 10 

### 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 BMDL 10 

### 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 BMD 10 

### 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 a djusted 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 expo sure 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 T CVP and that steady state inhibition occurs essentially after a single dose and within 21 days for other OPs, and a longer

term exposure would not be expected to result in a lower POD. The female BMDL 10 

### of 8.0

### Page 31 of 152

mg/kg/day associated with RBC A ChE 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 neurodevelopment al 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 BMDL 10 

### value o f 8.0 mg/kg/day, based on RBC A ChE inhibition and the BMD 10 

### 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 uncerta inty 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 brai n 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, reprod uctive, 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 sta te 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 ( BMDL 10 

### of 0.022 mg/L/day: BMD 10 

### of 0.12 mg/L/da y). 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

a gency’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 w as 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 f

or 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 pharmac odynamic) 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 Sprague

Dawley 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 dose

response relationship for neurodevelopmental effects (see Section 4.4)).

4.6.2 Recommendations for Combining Routes of Exposure for Risk Ass essment

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 Classifi cation 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 e vidence of thyroid c

- cell adenomas, and adrenal pheochromocytomas in the rat, as well as mutagenicity concerns. A cancer potency factor (Q 1 * 

### ) of 1.83 x 10

- 3 

### (mg/kg/day)

- 1 

### was estimated using the Weibull 83 time

- to

- tumor model. A 3/4 body weight scaling fa ctor 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 Non

Occupational 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) BMDL 10 = 8.0

mg/kg/day UF A = 10x

UF H =10x FQPA SF = 10x Acute RfD =

0.08 mg/kg/day aPAD = 0.008 mg/kg/day Subchronic Oral Toxicity Study (MRID

43371201)

– Ra t

BMD 10 = 10.49 mg/kg/day, based on female RBC A ChE inhibition

Acute Dietary (Adults 50

- 99) BMDL 10 = 8.0

mg/kg/day UF A = 10x

UF H =10x FQPA SF =
1x Acute RfD = 0.08

mg/kg/day aPAD = 0.08 mg/kg/day Subchronic Oral Toxicity Study (MRID

43371201)

- Ra t

BMD 10 = 10.49 mg/kg/day, based on female RBC A ChE inhibition

Steady State Dietary (all populations, except adults 50

- 99) BMDL 10 = 8.0

mg/kg/day UF A = 10x

UF H =10x FQPA SF = 10x Steady State RfD

= 0.08 mg/kg/day ssPAD = 0.008 mg/kg/day Subchronic Oral Toxicity Study (MRID

43371201)

– Ra t

BMD 10 = 10.49 mg/kg/day, based on female RBC A ChE inhibition

Steady State Dietary (Adults 50

- 99) BMDL 10 = 8.0

mg/kg/day UF A = 10x

UF H =10x FQPA SF =
1x Steady State RfD

= 0.08 mg/kg/day ssPAD = 0.08 mg/kg/day Subchronic Oral Toxicity Study (MRID

43371201)

– Ra t

BMD 10 = 10.49 mg/kg/day, based on female RBC A ChE inhibition

Incidental Oral (steady state) BMDL 10 = 8.0

mg/kg/day UF A = 10x

UF H =10x FQPA SF = 10x Residential LOC

for MOE = 1000 Subchronic Oral Toxicity Study (MRID

43371201)

– Ra t

BMD 10 = 10.49 mg/kg/day, based on female RBC A ChE 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 ) BMDL 10 =0.022

mg/L/day (males) UF A = 3x

UF H =10x FQPA SF = 10X Residential LOC

for MOE = 300 Subchronic Inhalation Toxicity Study

(MRID 48803501 )

– Ra t

BMD 10 = 0.12 mg/L/day, based on RBC
A ChE inhibition in both sexes

Cancer (oral, dermal, inhalation) Classification: A possible human (Group C) carcinogen

. Q 1 * = 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.
BMDL 10 = benchmark dose lower limi t 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 c hronic 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 r elationship 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.

I nhalation ( steady state ) BMDL 10 =0.022

mg/L/day (males) UF A = 3x

UF H =10x
UF DB = 10x* Occupational

LOC for MOE

= 3 00 Subchronic Inhalation Toxicity Study

(MRID 48803501)

- Ra t

BMD 10 = 0.12 mg/L/day, based on RBC
A ChE inhibition in both sexes

Cancer (oral, dermal, inhalation) Classification: A possible human (Group C) carcinogen

. Q 1 * = 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); UF DB = database uncertainty factor; MOE = margin of exposure. LOC = level of concern. RBC = red blood cel l. BMDL 10 = 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 as sessments. 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 du e to uncertainty in the human dose

- response relat ionship 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 effec ts 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 th at 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 exist ing 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 pestici de 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 makin g 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 Ti er 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.

U nder FFDCA section 408(p), the a gency must screen all pesticide chemicals. Betw een 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, 2013 9 

### and 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 re quired Tier 1 assay data. The a gency 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/tetrachlorvinphos

083701_2015

- 06

- 29_txr0057147.pdf ). For further in formation 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 website 10



### .

9 See http://www.regu lations.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 R esidue 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 ( D P# 1 99644, 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

- trichloro acetophenone, 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

- 7 

### torr (25°C). The compound is hydrophobic (Log K ow 

### of 3.53). TCVP hydrolyzes in water at a pH

- dependent rate. Hydrolysis is relatively rapid in alkaline water (half

life 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). Hydro lysis 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 ou tdoor 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, whi ch 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 Com parison 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 TCPE diol 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 tetrachlorvinp hos 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 tetrachl orvinphos [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 c oncern 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, TC VP 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 t able 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 : D P# 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 r egistered 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 der mal 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 treatment s; 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, a nd 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, D 320857

, 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 shorte r 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 w ere 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 dif ferent proposed method ( Method 14020.6106 ) and an associated ILV study ( Method 14020.610 7) w ere subsequently subm itted to the a gency (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 m ethod SCR/006 (MRID 47369201) is considered acceptable as a confirmatory method. T he 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
T he available magnitude of the residue study for dairy cattle reflect a combination of two treatments: oral admini stration 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 th ree 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 kidn ey, 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 re gistered 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 kid ney, 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; n or 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 tric hlorobenzene 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 ac id).

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 singl e 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 (PRZM

GW) 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 duratio n ( 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 (s teady state) average daily food and drinking water expos ures

. For t he two

- day average
assessments, using a 21

- day forw ard

- rolling average water distribution file provide s an accurate overall estimate of the 21

- day (“steady

- state”) average daily exposures at the per

- capita 95 th 

### 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 duratio n rather th an a 21

- day exposure duration. Si nce 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 average s 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 provide s an acceptable estimate of steady state exposure for food and drinki ng w ater for use in risk assessment and will not underestimate the risk.

TCVP d ietary 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. Model

der ived estimated drinking water concentrations (EDWCs) were provided by the E nvironmental Fate and Effect Division (EFED). EDWCs were based on spot applications to kennels, poultry droppings, garbage and manure piles, and corrals and were directly incorporat ed 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

asses sment. The factor was calculated by determining the ratio of parent TCVP to total residues of concern in the livestock residue studies (see Table 2 , D 426985 ).

5.4.2 Percent Crop Treated Used in Dietary Assessment

For the acute and steady state analyses, t he maximum estimated percent livestock tr eated 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 99.9 th 

### 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 e xposures 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 p re

- 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
99.9 th Percentile 99.9 th Percentile 99.9 th 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 99.9 th 

### percentile of exposure is 4 3 % of the ssPAD for children (3

- 5 years old), the most highly exposed populat ion subgroup (Table 5.4 .4 below). Steady state e xposures 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 . Re sults of Steady State Dietary Exposure Analysis for TCVP Food only , Drinking Water only, and Food plus Drinking Water Population Subgroup ss PAD

(mg/kg/day) 1 Food only Drinking Water only Food plus Drinking
Water
99.9 th Percentile 99.9 th Percentile 99.9 th Percentile Exposure (mg/kg/day) %

ss PAD Exposure

(mg/kg/day) %

ss PAD Exposure

(mg/kg/day) %

ss PAD
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 Q 1 

### * of 0.00 183 (mg/kg/day)

- 1 

### to 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 Subgroup 1 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 pos t

- 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 9 th 

### Circuit , which was filed as a result of the 2014 residential assessment and EP A’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 inc lusion of the 10X FQPA safety factor.

 T here 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 bel ow)

.

 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 t wo 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

asse ssments, 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 o ld) 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 th e 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 s tudies 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

ass essment.

Exposure/risk estimates are provided using residue transfer data from both the amitraz and Davis pet collar studies sinc e t h e 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 th e 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 ris k estimates for exposures to pet collar treated pets are to be considered preliminary and are presented for purpose s 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 opportuni ty 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 §26.170 6 (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 study 13 

### has concluded that the methods used for conduct of the collection of transfera ble 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 coll ected 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 fr om 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 physiolo gically 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 Res idential Assessment

Residue Transfer Study Used in Current

Risk Assessment Methodology Non

- Cancer Residue Transfer Assumption Cancer Residue

Transfer Assumption

Propoxur pet collar 1 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 collar 2 Yes 0.14% (mean Day 0) 0.047%

(mean over 28 days)

Davis pet collar 3 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 Res idential 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 Pro poxur

– 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 Ins ecticide 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 su pported 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 amoun t 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, t he 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 confirme d 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 th e 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 th e 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 SOP s 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 expo sure and dose for residential han dlers 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 r eside ntial handler (adults) no n

- 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 Q 1 

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

### * = 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 Q 1 

### * 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

- 8 

### to 10

- 7 

### , and for pump/trigger sprays range from 10

- 9 

### to 10

- 8



### .

Pet Collars: 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

- 7 

### range when assuming a dust formulation

.
A summary of residential handl er 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 pro ducts (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) exposu re (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 no t performed as inhalation exposure is expected to be negligible from contact with treated pets. A n inhalation exposure assessment was performed for occupational pet handlers (i.e., veterinarians, veterinary assistants, and groomers) and this exposure scen ario is considered protective of any potential low

- level post

- application inhalation exposure that could result from these types of uses (see S ection 8.0 below)

. For the adult cancer post

- application assessment, only dermal exposures are quantitatively ass essed.

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 ris k estimates can be found in D426 984.

Residue Transfer Assumptions: Surrogate and chemical

- specific residue transfer studies were

u sed 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 (M RID 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 great er 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 a gency 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 a gency 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 am itraz 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 res idue transfer values are used for the assessment of risks occurring over short

- or intermediate

- term, or steady state durations; however, the Davis study presents o nly a 12 day mean transferable residue value. Until the Davis study has undergone HSRB revi ew, 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

- Ca ncer Post

- application Exposure and Risk Equations The algorithms used to estimate non

- cancer exposure and dose for residential post

- applic ation 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), r esidential post

application non

- cancer incidental oral (h and

- 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 con cern 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 assumptio n: With use of the amitraz pet collar residue transfer study and SOP inputs specific for liquid formulation products, residential post

application 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 s tudy 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

- applic ation 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 ris k estimates can be found in D426 984.

Residue Transfer Assumptions: For the cancer post

- appli cation 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 F AR 

### of 0.022% and 0.18% for dusts/powders and pump sprays, respecti vely. Due to the reasons described above (under

“ Residential Non

- Cancer Post

- Application Exposure Data and Assumptions”)

, maximum residue value s 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 Equati ons 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 Q 1 

### * that has been calculated for TCVP ba sed on dose response data in the appropriate toxicology study (Q 1 

### * = 1.83 x 10

- 3 

### (mg/kg/day)

- 1 

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

- application exp osure can be found in Appendix D of D426984

.

It should be note d 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 a genc y'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. Th ese 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 a gency’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

- 7 

### to 10

- 6 

### and, for TCVP dust/powder products estimated cancer risks are 10

- 7



### .

Pet Collar

s: 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 expos ure 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

- 6 

### to 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 usi ng 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 bui ldings 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 wa s 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 fo r 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 acu te 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 exposur e pathways. The steady state aggregate risk assessment combines steady state exposures from food, drinking water, and residential ( pet product) uses. Steady s tate aggregate risk assessments were performed for adult handlers (females

, age 13

- 49 y ears ) appl ying registered pet collars, dust/powders, and pump/trigger spray products to cats and dogs. Residential post

- application

### Page 55 of 152

s teady s tate 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 consist s 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 (1 000 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 Exposure 3 Aggregate ARI

(food, water, and residential ; LOC = 1 ) 4 MOE (LOC = 1000) ARI

(LOC = 1) MOE

(LOC = 300) ARI

(LOC = 1)
Pet Collars (Liquid A ssumption): 2012 Residential SOPs (Spot

- on Surrogate Data )

2596

- 49; Cat 11g 5,100 5.1 N/A 5 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 A ssumption): 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 Exposure 3 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 post

application 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 consist s of only incidental oral exposure for chi ldren.

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 a ssessments were not presented assuming solid formulation and the Davis study; th ose 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

BMDL 10 mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food and Water Exposure mg/kg/day Residential

Exposure (Incidental Oral) mg/kg/day 3 Total

Exposure mg/kg/day 4 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

BMDL 10 mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food and Water Exposure mg/kg/day Residential

Exposure (Incidental Oral) mg/kg/day 3 Total

Exposure mg/kg/day 4 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

BMDL 10 mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food and Water Exposure mg/kg/day Residential

Exposure (Incidental Oral) mg/kg/day 3 Total

Exposure mg/kg/day 4 Aggregate

MOE (food, water, and residential) 5

Pet Collars ( S olid A ssumption): 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

BMDL 10 mg/kg/day LOC 1 Max Allowable Exposure 2 mg/kg/day Average

Food and Water Exposure mg/kg/day Residential

Exposure (Incidental Oral) mg/kg/day 3 Total

Exposure mg/kg/day 4 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) = BMDL 10 /LOC

3 Residential Exposure = Oral exposure only (Appendix H ).

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5 Aggregate MOE = [BMDL 10 / 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 adu lt 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, a nd pump/trigger sprays) result in residential handler cancer aggregate (residential and dietary) risk estimates in the 10

- 6 

### range.

All dust /powder and pump/trigger spray product scenarios result in residential post

- application cancer aggregate (residential and dietary) risk estimates in the 10

- 6 

### range. When collars are assumed to be liquid formulations, post

- application cancer aggregate risk estimates are n the 10

- 6 

### range using the amitraz data an d are 10

- 5 

### to 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

Davi s )

.

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 Exposure

All 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

. 3 Aggregate Cancer Risk = (Q 1 *) (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 Exposure

Pet 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 1155 6

- 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

3 Aggregate Cancer Risk = (Q 1 *) (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 th ere 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 th e 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 activit y, 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 n ow 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 rega rding 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 Powd er: 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:

(9 a) Liquid: Backpack Sprayer (9 b) Liquid: Manually

- Pressurized Handwand (9 c) Liquid: Mechanically

- Pressurized Handgun (9 d) Liquid: Backrubber or Facerubber (1 0 a) Wettable Powder: Backpack Sprayer (1 0 b) Wettable Powder: Manually

- Pressurized Handwand (1 0 c) Wettable Powder: Mechanically

- Pressurized Handgun (1 0 d) Wettable Powder: Handheld Fogger (1 0 e) Wettable Powder: Stationary Fogger (1 0 f) Wettable Powder: Rotary Duster (1 0 g) Wettable Powder: Plunger Duster (1 1 a) Dust: Self

- Treating Dust Bag (1 1 b) Dust: Shaker Can (1 1 c) Dust: Rotary Duster (1 1 d) Dust: Plunger Duster (1 2 a) Paint: Brush or Roller (1 2 b) Paint: Airless Sprayer (1 3 ) 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, Monitori ng 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 applyin g WP with mechanically

- pressurized handwand) for the o ccupational 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 equipm ent (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 r equired for the occupational hand l ing 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 presente d in Appendix L of th is 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 equip ment (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 o f 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 sce nario.

Occupational Handler Cancer Exposure and Risk Equations

Cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a n 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 value s. 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

- 5 

### for 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 becau se, 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 livestoc k 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 coveral ls, or respiratory protection

.
A summary of occupational cancer risks as estim ated 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 pri vate/farmer handlers and Table K .2 risks for contract/commercial handlers. For risk management pu rposes, 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 ant icipated for this use pattern

. R estricted 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 Work er 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) datab ases 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 S tudy ( 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 resol ving 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

- Pesti cides, there does not appear to be a concern at this time that would warra nt further investigation. The a gency 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 OP P’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 dat a 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 exp osure information available since 2006.

As describe d 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 epide miology 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 Cu mulative 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, D 199644, 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, D 43528, 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, D 320857

, 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, Tetrachlorvinph os (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, T etrachlorvinphos: Occupational and Residential Exposure Assessment for Registration Revie w

.

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

- Appli cation 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 Ris k Estimates Appendix L. Summary of TCVP Labels and Use Directions

### Page 68 of 152

Appendix M. Calculation of Inhalation Human

- Equivalent Concentrations (HECs) and Human

Equivalent 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 LD 50 = 1480 mg/kg (M) 465

- 965 mg/kg (F) III

870.1200 Acute Dermal

– Rabbit 41222505 LD 50 > 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 d ose 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 5 0 mg/kg, males had 54% and
females had 23% brain cholinesterase inhibition.

BMDL 10 = 6.7 mg/kg/day

BMD 10 = 9.9 mg/kg/day, based on female RBC ChE inhibition

BMDL 10 = 12.2 mg/kg/day

BMD 10 = 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.

BMDL 10 = 8.0 mg/kg/day

BMD 10 = 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 d eposition 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 sexe s. At 467 mg/kg/day, females had a 24% brain cholinesterase activity inhibition, although statistical significance was not attained.

BMDL 10 = 8.0 mg/kg/day

BMD 10 = 10.49 mg/kg/day, based on female RBC ChE inhibition

BMDL 10 = 26.3 mg/kg/day

BMD 10 = 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 m g/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 i n squamous metaplasia of the larynx in both sexes, and an increase in follicular cell hyperplasia of the thyroids in
both sexes.

Sex/Age Compartment BMD 10 BMDL 10 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) Materna l NOEL = 375 mg/kg/day
Maternal LOEL = 750 mg/kg/day, based on mortality, abortions, and red vaginal fluid. Developmenta l NOAEL = 375 mg/kg/day Developmenta l 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)
Of fspring 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), base d 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 **).
NOA EL = 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 cel l 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 fasciculat a 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 pheoch romocytomas 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

ma les, 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 con cen trations 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) MRI D 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 for m 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/cm 2 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/cm 2 dose is 9.57% following 10

- ho ur

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% a nd ↓ 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 indicat e that the fetuses are more
sensitive than the dams.

Classification: This in vivo comparative ChE study is classified as

A cceptable/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 ex posure 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, d uplicate 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 tha t 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, n o a dditional 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 t he 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 BMD 10 and

BMDL 10.

This study is classified as A cceptable/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, n o 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 inhib ition (≈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 ma gnitude 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 BMD 10 and BMDL 10 of adults and PND11

pups.

BMD 10 s and BMDL 10 s for Adult Rat and PND 11 Pup Cholinesterase

RBC BMD 10 RBC BMDL 10 Brain BMD 10 Brain BMDL 10 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 sens itivity 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

- in

requirement 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 -

- 75 A ♀24

- 28% B ; ♂42

- 64% C ♀22

- 38%; ♂19

- 40%

MRID 48294601 Acute CCA (PND 21) RBC

Brain -

- 75 A ♀27

- 36%; ♂19

- 49% ♀25

- 54%; ♂24

- 45%

MRID 48294601 Acute CCA (young adult) RBC

Brain -

- 75 A ♀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 - 75 A

- 31%

MRID 48291101 Gestational CCA (fetuses) RBC

Brain - 75 A

- 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

A Lowest dose tested; B pre

- test was 27%; C pre

- test was 34%; D 30% 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 data 14 

### . 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

ev aluation 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 toxic ity 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
A ChE

- inhibiting pesticides. Model runs for A ChE activity were conducted with an appropriate benchmark response level (10%). As such the BMD 10 

### (estimated dose to result in 10% change from background levels) and BMDL 10 

### (the lower 95% confidence level on the BMD 10 

### ) are provided in the output. Statistical (e.g., goodness of fit value s) 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 BMDL 10 

### for A ChE inhibition in the adult female RBCs were similar in the 13

- week subchronic study and the 21

- day oral toxicity study (8.0 mg/kg/day vs 6.7 mg/kg/day, respectively). Although data from the shorter duration study resulted in a slightly lower BMDL, visual examination of the modeled data provided greater confidence in the 13

- week study. For inhalation exposure, the adult male was about twice as sensitive as the adult female (0.023 mg/L in males vs 0. 050 mg/L in females).

Table B.1. Results of BMD Exponential Modeling for Brain and RBC A ChE Data on TCVP, Repeated Oral Dosing Studies in Rats, Ranging in Duration from 21 days to 2 years.

TCVP Study Age/Sex Compartment BMD Results
BMD 10 

### BMDL 10



### 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 A ChE Data on TCVP, Repeated Oral Dosing Studies in Rats, Ranging in Duration from 21 days to 2 years.

TCVP Study Age/Sex Compartment BMD Results
BMD 10 

### BMDL 10 

### 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 0.02 2 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 Phy sicochemical 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, pK a non

- ionizable (MRID 41222503) Octanol/water partition coefficient, Log(K OW ) 3350 average K OW 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 Properties 1 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 Molecular weight: 365.96 g/mol VP: 2.6 E

- 0 7 torr Solubility: 11.6 mg/L Log Kow: 3.53
Koc: 520

- 1100 L/kg oc

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 Molecular weight: 351.94 g/mol VP: 4.27 E

- 0 8 torr Solubility: 3.768 mg/L Log Kow: 3.75
Koc: 702

- 827 L/kg oc

1

- (2,4,5

- trichlorophenyl)ethanediol



### C(O) (CO) c1cc(Cl)c(Cl)cc1Cl Molecular weight: 241.5 g/mol VP: 4.37 E

- 0 6 torr Solubility: 250 mg/L Log Kow: 2.37
Koc: 29

- 36 L/kg oc

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 Molecular weight: 225.5 g/mol VP: 2.37 E

- 0 4 torr Solubility: 123 mg/L Log Kow: 3.43
Koc: 319

- 359 L/kg oc

TCPEone (CO300)

2,4,5

- t richloroacetophenone



### CC(=O)c1cc(Cl)c(Cl)cc1Cl Molecular weight: 223.5 g/mol VP: 6.32 E

- 0 3 torr Solubility: 27.4 mg/L Log Kow: 3.61
Koc: 492

- 1,828 L/kg oc

### Page 84 of 152 Chemical Name Structure Physical/Chemical Properties 1

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: 2.11 E

- 0 5 torr Solubility: 250 mg/L Log Kow: 3.68
Koc: 494

- 608 L/kg oc

TCBA (SD 15917)

2,4,5

- Trichlorobenzoic acid



### C(=O)(O)c1cc(Cl)c(Cl)cc1Cl Molecular weight: 225.5 g/mol VP: 5.52 E

- 0 4 torr Solubility: 35.3 mg/L Log Kow: 3.47
Koc: 157

- 166 L/kg oc

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. De s

- 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 byproduct s 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 Rate 1 (lb ai/pet) Amount

Handled Daily 2 Dermal Inhalation

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

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) × De rmal Ab sorption 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 a i) × Application Rate (lb ai/pet) × Area Treated or Amount Hand led (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 Estimat es 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 Rate 1 (lb ai/pet) Amount

Handled Daily 2 Dermal Inhalation

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

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 0.000 0 94: 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 Estimat es 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 Rate 1 (lb ai/pet) Amount

Handled Daily 2 Dermal Inhalation

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

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) × De rmal Absorption Factor (9.6 %) ÷ Body Weight (69 kg). Dermal dose presented only for purpose of calculation of cancer risks for re sidential 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 Hand led (pets/day) ÷ Body Weight (69 kg).
6 Inhalation MOE = Inha lation 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 LADD 1,2 

### Cancer Risk Estimate 3



### 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 L ifetime A verage D aily D ose (mg/kg/day) = Dermal LADD (mg/kg/day) + Inhalation LADD (mg/kg/day). 2 Dermal and Inhalation LADD equations provided in Appendix A of D 426 984

. 3 Cancer risk estimates = Total LADD × Q 1 * , where Q 1 * = 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 LADD 1,2 

### Cancer Risk
Estimate 3



### 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 D426 984

. 3 Cancer risk estimates = Total LADD × Q 1 * , where Q 1 * = 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). In cidental 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 

### MOEs 3 

### 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). In cidental 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 

### MOEs 3 

### 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 D426 984.
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 

### MOEs 3 

### 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 

### MOEs 3 

### 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). I ncidental 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 

### MOEs 3 

### 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). I ncidental 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 

### MOEs 3 

### 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 

### MOEs 3 

### 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 

### MOEs 3 

### 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 o f 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 LADD 1,2 

### Cancer Risk Estimate 3



### 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 LADD 1,2 

### Cancer Risk Estimate 3

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 LADD 1,2 

### Cancer Risk Estimate 3



### 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 LADD 1,2 

### Cancer Risk Estimate 3



### 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

A ppendix J

. Summary of Occupational Handl er 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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

(6 a ) RTU Pet Collar Applications 1

- 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. Rate a (lb ai/ unit) Area

Treated b (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

(6 b ) RTU Pet Collar Applications

Dust 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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

Manually

Pressurized 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 1 15 of 152 Table J .1. TCVP Occupational Handler Non

- Cancer (Steady State) Risk Estimates

. Exposure Scenario Crop or Target App. Rate a (lb ai/ unit) Area

Treated b (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 20,000 sq 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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
Manually

Pressurized 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. Rate a (lb ai/ unit) Area

Treated b (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 1,000 birds 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 20,000 sq ft 0.15 0.029 0.015 No Data 34 170 340 No Data

Poultry (Wire Cage)

– Direct Applied 0.00010 20,000 birds 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. Rate a (lb ai/ unit) Area

Treated b (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 1,000 sq ft 0.0074 0.0015 0.00074 No Data 680 3,400 6,800 No Data

Poultry (Wire Cage)

– Direct Applied 0.00010 1,000 birds 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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

(6 a ) 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. Rate a (lb ai/ unit) Area

Treated b (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

(6 b ) 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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: Manually

Pressurized 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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 20,000 sq 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. Rate a (lb ai/ unit) Area

Treated b (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: Manually

Pressurized 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. Rate a (lb ai/ unit) Area

Treated b (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. Rate a (lb ai/ unit) Area

Treated b (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 1,000 birds 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 20,000 sq 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 20,000 birds 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 1,000 sq 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 1,000 birds 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. Rate a (lb ai/ unit) Area

Treated b (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: Fe ed 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 fee ding, 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 rati on. 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

concentr ate 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 prod uct

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 am ount 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 n ot 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 b ody 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 dail y 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:

Baselin e 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, an d 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 al so 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 pre

packed 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

wat ering 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 th e 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 s hould 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 gallo n 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 d roppings. 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 appl y 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 gallo n 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,

m echanical 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 spray er 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 sol ution 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 ev ery 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 prope r 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 infesta tion.

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 t he 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

- 16 4 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 m onths 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, c overalls, 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 con trol 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 f or 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 f or a small cat. Spray 25

- 35 strokes for a large cat. More spray may be needed for longhaired cats. 1

2596

- 140 Cats 3

(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 i nches 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 Cats 3 (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 pharmacodynami c) 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 aer odynamic 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

( μ m) 3 GSD

( μ m) 3 Respiratory

Region for Effect 4 RDDR hours/day days/week 2

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

- to

human ratios of daily (hours/day) and weekly (days/week) exposures are app lied 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.

POD a d justed 

### = 0

. 02 mg

L × 6 h r / day

8 h r / 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 exp osures, 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 resultin g 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 HEC s (presented in Table M .3 below).

HEC = POD adjusted 

### × 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

accoun t 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 sce narios 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 u sed 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 o n Different Handler Exposure Scenarios

Exposure Scenario Human Breathing Rate (L/min) HED Calculation Inputs

AF 1

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/m 3 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 post

application NA NA 0.05050 50.50 NA NA NA

Indoor post

application 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 handle r which used the unrounded value of 0.022 mg/L.