### UN I T ED STA TES E NVIRONMENTAL PROTECTION AGENCY WA SHINGTON , D .C. 20460

OFFI CE OF C HE MI CAL SA FETY AND POLLUTION PREV ENTION 

### MEMORANDUM Date : 

### Decembe r 21 , 20 15
SU BJEC T: 

### Te trachl orvi nph os (TCV P ): R espo nses to Argume nts Presented in the Natural Resourc es Defe n se Council, Jn c.'s (N RD C) Aug. 5 , 2015 Op e nin g Brief in 

### N RD C v. 

### EPA , Case No. 15-70 025 (9 111 

### Cir.)
P C Co d e: 

### 083701 , 083 702 Petition No.: 

### NA Risk Assess me nt T y p e: 

### NA TXR No.: 

### NA MR ID No.: 

### NA DP Barcodc : 

### 430589 Registration Nos.: 

### NA Regulatory Act ion: 

### Re spo nse to Comments Case No.: 

### NA CAS No.: 

### 22248-79-9

F ROM: 

### Wade Britton , MPH , Env iro nm ental H ea lth Sc ientist Ri s k Assess m ent Branc h IV Health Effec ts Divisi o n ( H ED , 7509 P) THRO UG H: 

### Michae l Metzger , Branch Chief

## ~~**~** Ri sk Assessme nt Branch VN II

TO: 

### H eal th Effec ts Di vis ion ( H ED , 7509 P) James Park er , Chemical Revi ew Manager Melissa Grable , Team Lead Ri s k Management and Impl e m entation Branc h I Pe st ic id e Re-evaluation Divi s io n (7508 P)

This docume nt constitutes th e EPA's re s po nse to arguments prese nted in th e Natu r al Resources Defen se Cou ncil , Inc .'s (NRDC) Aug. 5 , 20 15 Opening Bri e f in 

### NRDCv. EPA , Case No

. 15

- 70025 (9 111 

### Cir. ) (Op e nin g Briet). EPA her e in r es ponds , o n a point by point bas i s, to NRDC 's argument s s pecifically pert ainin g to the Hea lth E ffects Di vision ' s ( HED) 20 14 r esidential exposure assess m e nt for T C VP pet product uses, conducted in re s ponse to NRDC 's 2009 petiti o n to cancel all pet uses ofTCV P. 1 

### In addition , th e 2015 T CV P human health draft ri sk assessment for re g is tr ation re v i ew 2 

### takes into accou nt , whe r e ap propri ate , the arguments prese nted in

1 W. Brill on, 11 / 05 / 14 , D 420283, R esi dential Exposure Assessmen t in R es po nse to the Natural R eso urces Defen se Council Petit ion to Ca ncel All Pet Uses for Terrachlorvinphos. 2 D. Drew , et.al, 12/21/20 IS , D 4 I I095, Te rrachlo rvi nphos (TCV P) Hum an Health Draft Ri sk Assess ment ( O RA) for R

egistration Review.

### NRDC's Opening Brief. For any argument presented by NRDC that is not explicitly addressed in the 2015 draft risk assessment , this document explains EPA 's consid eration of that argument in the context of drafting the 2015 draft risk assessment.

J. N RD C A rgum ent: NRD C a r g u es th a t th e U.S. Env ironm e nt a l Pro t ec ti o n Age n cy (E P A o r th e age n cy) in co rrec tl y elimin a t ed th e pres umpti ve t enfold m a r g in o f sa fe ty id e ntifi ed in sec ti o n 4 08 ( b )(2)(C) of th e Fe d e ral Fo od , Dru g, a nd C o s m etic Act (FFD CA), 21 U

. S

. C. 

### § 346 (b )(2)(C), to prot ect in fa nt s and children . 

### NROC argues that, in conducting the 2014 TCVP resident ial assessment , EPA did not adequately explain why the 

### " IOX safety factor " was reduced to IX , 

### or why blocking ten percent of acetylcholinesterase was not hannful. NRDC points out that , following the release of the 20 14 TCVP resid ential assessment reduc ing the I 

### OX safety factor to IX, 

### the revised risk assessment for ano ther chemical

- chlorpyrifos

- completed in the context of Registration Review of that chemical 3 

### retained the I 

### OX safety factor.
E P A Res p o n se : 

### Since the time of the 2014 TCVP resid en tial assessment , EPA has revi sed its approach relative to cons iderati on of the FQPA 1 

### OX factor based on its recent risk assessment for chlorpyrifos and evaluat ion of available research for all organophosphates (hereafter OPs). Newer lines of research on OPs in the areas of potential adverse outcome pathways (AO Ps) , in vivo animal stud ie s, and notably epidemi ological s tudi es in mothers and children , have raised uncertainty abo ut the age nc y ' 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 th e agency over the last several years as part of efforts to develop a r isk assess me nt for chlorp yri fas ( 042448 5, 0. Drew et al, 12/29/2014). 4 

### A detailed review of the epidemiological studies used in this revi ew can be found either in the 2014 ch lorpyrifos risk assessment or in the 2015 literature rev iew for other OPs (OPP/USEPA; 0 33 1251 ; 9 1 15/ 15). 5 

### Ultimately, the agency reta ined th e FQPA 1 

### OX Safety Factor (SF) in the 20 14 chlorpyrifos revised risk assessmen t based, in large part, on the findings of these epide miol og ical studies. In 2015 a literature review was co nducted expand in g the scope of that co mpl eted for chlorpyrifos to include consideration of the epidemiological data on any OP pesticide. This included study designs besides prospective cohort studies, and non-U

. S

. ba sed studies; e ight re leva nt studies we re evaluated. The 20 I 5 re view concluded that , at this time , MOA(s) /AO P(s) have not been established for neurodevelopmental outcomes. The growing body of literature docs demonstrate; however, that OPs are biologically active on a numb er of processes that affect the developing brain. Moreover , there is a large body of in vivo 

### laboratory s tudies wh ich show long-tenn behavioral effec ts from early life exposure, albeit at doses which cause AChE inhibition. EP A co n siders the results of the toxicological stud ies relevant to the human population , and as qualitatively supported by the res ults of epide miology studies. The agency acknow ledges th e

3 D. Drew

. Chlorpyrifos: Revised Human Health Risk Asse ss ment for Registration Review. 0424485. 12/29/ 2014. 4 The chlorpyrifos risk assessment can be found in the Federal docket at: l111p: '/\\'\\' \\'. regular ions. l!.O\' II !docket Dctai I: D'- EPA-I IQ -OPP-2008-0850 5 The 2015 literanire review for other OPs can be found in the Federal docket at: http: '' \\ \\ .rc!!ulations.co' :; !documcmDctail:D

- EP A-l IQ-OPP-2008-0 I I9-0015 

### Page 2 of 14

### lack of estab lis hed MOA/AOP pathway and unc ertainti es assoc iated with the lack of ab il ity to make s tron g causa l linkages and unknown window(s) of susce ptibility. These uncertainties do not undermine or reduce the confidence in the findings of the epidemiology studies. The epidemio logy s tudie s rev iewed in the 20 12/20 I4 and 20 15 li teratu r e rev iews represent different inve st igator s, location s, points in time , exposure assessment procedures , and outcome mea sureme nt s. Despite all these differences in s tud y des ign, with the exception of two negative studies in th e 20 15 litera ture rev iew (Guodo ng et a l, 2012; Oul hote e t a l, 2013), autho r s have identified associations with neurodevel opme ntal outcomes associated with OP exposure across four cohorts and twelve study citat ion s. Specifically, there is evidence of delays in mental dev e lopment in infan ts (24

- 36 months) , atte ntion prob lems and autism spec trum disorder in ear ly childhood , and intelligence decrements in school age children who were ex posed to OPs during gestation. In vest igators reported strong measures of statistical association across seve ral of these eva luations (odds rat ios 2

-4 fold inc r ea se d in some insta nces), and observed ev idence of exposures-response trends in some in stances, e.g., intelli ge nce measures. Section 408(b)(2)(C) of the FFDCA ins tructs EPA, in mak ing its " reasonable certainty of no harm " finding , that "(i]n the case of threshold effects, an additional tenfold margin o f safety for the pesticide che mical residue and other sources of exposure shall be applied for infants and child r en to take into account pote ntia l pre - and postnatal tox ic ity and completeness of data with respect to exposure and toxicity to infant s and children. " FFDCA § 

### 408 (b)(2)(C) further s tates that ··the Administrator may use a diff erent marg in of safety for the pesticide chemical residue o nl y if , o n the basis of reliab le data, suc h marg in w ill be safe for infants and children." Given the totality of the evidence , there is sufficient uncertainty in the human dose-response relati ons hip fo r neurodevelopmental effects which pre ve nts the agency from reducing or r emovi ng the s tatutory 1 OX 

### FQPA Safety Factor. For th e 2015 TCY P draft ri sk assessment (DRA ) (0411095 ), a value of l 

### OX has been retained. Similarly , a database uncertainty fac tor of I

### OX 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 do ses which e licit AChE inhibition and those which arc assoc iated with neurodevelopmental outcomes and will consider such outcomes in future risk assessment r efinements i 

## r warranted. A full discussion of the literatur e revi ew on neurodevelopmental effec ts can be found refere nced in Section 4.4 of the TCY P ORA (04 1 1095). 6


### 2. N RD C A rgum e n t: NRD C a r g u es that without a c hemical -s p ecific s tud y, EPA s h o uld ha ve u s ed th e 201 2 R es id ential S OP s d e fault of tw o perc ent to assess ri s k s fr o m p et c oll a r ex po s ures. 

### NRDC argues that EPA 's 2012 Resid e ntial SOPs state that , " if chemical s pecific [transfer residue] mea s urement s ar e not availab le, then a s t andard va lue fo r the fraction of active ingredient availab le (FAR) for transfer is used [NRDC Opening Brief, p.62].'" Further , EPA 's TCYP assessment sta t es that , · ' [i]t i s [EPA] policy to use the best available data to assess exposure, " and "[w ]here chemica l or formu lat ion-specific exposu r e data were ava il able , th[o]se da t a were used

6 The TCVP ORA can be found in the following Federal dockets: http: I \\" w.reg,ulations.gov .';/ !docketDctail:O E PA-l IQ-OPP-2008-0316 and h!!n: ''"".regulations.co' tl !dockc tOcwil:D EPA -I IQ-OPP-2009-0308 

### Page 3 of 14[NRDC Opening Bri ef, p. 53). " As such, NRDC argues that EPA s hould not have relied on the surrogate pet fur residue tran sfer data from a recent ly study conducted for the active ingredient , propoxur. Further , although E PA discussed two o th er stud ie s using two different chem ica ls, propoxur and deltamethrin, and used the more co nservativ e mean percen t residue transfer resulting from the propoxur study for estimation of TC VP post-application risk , NRDC argues that th e recommended default should have instead been app li ed. 

### EPA Response: The 2014 re s idential assessment addressed in detail the decision to use non-chemical-specific expos ure data for assessment of risk s from the TCV P pet colla r formu lation. The assess m e nt describes that it is EPA policy to use the best available data to assess exposure. Further, where chemical

- or form ul ation

- specific exposure data are available, these data are used to conduct the assessment of res ide ntial handler and post-app li cation expos ure s or integrated with other data as appropriate. No exposure data were availab le specific to TCVP pet collars at the time the risk assessment was completed

. 

### It should be noted that TCVP- specific exposure (i.e., residue transfer) data are available for the TCVP contain in g du st/powder and pump spray products but these data would best be considered in risk assessment only for the specific product types (i.e., formulations) because of their inherent basic differences. In comparison to other formu lati ons used fo r pet pest control (i.e., dusts, spo t-on s, liquid sprays), it is well known that pet collars are unique and , thus , result in considerably lower percent residue transfer values which was the rationale used as the basis for opting to the use of the propoxur pet collar transferable residue data (i

. e., product type is the key considerat ion). This was clearly outlined in th e 20 14 resid e ntial risk assessment which stated the following:
"When other pet produ ct formulat ions arc applied to a treated pet , it can 

### be r easonably assumed that the entire amount of that applied ( i. e., the application rate) is ava il able on the hair coat of the animal for transfer to the exposed individual. For example, the labeled amount of th e TCV P pump/ trig ger spray product can be u sed direct ly in the assessment of ex posure/ risk because it is assumed this amount is available on the surface for contact. Pet co llar formu lations operate by slowly releasing the ai from the collar medium , makin g them efficac io u s for pest treatm e nt over lo nger periods of time. Due to this activity , it can be difficult fo r the ri sk assesso r to determine the amoun t whic h i s initially avai l able on th e animal because the majority is retained within th e co llar. " Given the above considerations , EPA relied on expos ure data specific to the assessment of postapplication risks from a pet collar product. While TCVP-containin g collar residue data were not available for assess ment of post-application exposures from the use ofTCVP pet co ll ars , tw o pet collar formulation

- specific po s t-application exposure stud ies were available at the time of the 2014 residential assessment; a propoxur pet collar study (M RID 44858990 I ) and a deltamethrin pet collar residue transfer stud y (MRTD 49350 I 0 I ). B oth s tudi es were conducted in a manner consistent with current human e thical s tandards and were considered scientifically acceptable for use in post

- application risk assessment. The propoxur pet collar study resulted in mean percent re sidue transfer o n Day 0 in excess of that of th e deltamethrin s tud y; 0.072% and 0.003% of the collar contents, respectively. Therefore , fo r the 20 14 re s idential assessment, the more conservative mean percent residue transfer resulting from the propoxur study was used as a surrogate for es timati on of TCVP post-application risks.
Page 4of14

### Since the 2014 residential assessment, an amitraz pet collar residue tran sfer s tud y was subm itted that was also conducted in a manner consistent w ith current standards. This study results in a higher mean percent residue transfer on the day of application than the other available studies (0. 14 %) and , therefore, has been used as th e basis for the assessment of post

- application risks from the TCVP pet collars

. Further , as noted in th e subsequent response , HED has also used the Davis s tud y7 

### for estimat ion of post-applicat ion risks from TCVP pet co ll ar exposures . These data (summarized in greater detail in Sect ion 5.3 of the 2015 Occupational and Residential Exposure Assessment for Registration Review 8 ) 

### result in a mean residue transfer (Study 1 , 12 days after collar placement) of 0.40%. The Davi s study, which is pending review by the Office of the Science Advisor (OSA) Human Studies Review Board (HSRB) 9

, 

### further supports that pet collar formulations differ from other types of pet products and that the default pet residue transfer value of 2% would sig nificantly overestimate res idue tran sfe r from collars. While the three surrogate pet collar residue transfer studies are not chemica l- specific, these data are th e best avai labl e su 11"ogate for TCVP collars and offer a reali s tic refinement from the hi g hend default fraction application rate (FA R) 

### transfer factor recommended (2%) in th e updated 2012 Residential SOPs which reflects other pet product types (e.g

. , dusts and sprays). The default FAR, 

### 2%, stipulated in the 2012 Res identia l SOPs: Treated Pets, is the 90th percentile of Day 0 (i.e. , the first 24 hours fo ll owing application) measures from all transferable residue data available at that time regardless ofproduct type. Of the 7 stud ies which are the basis of the 2% default r esidue transfer value , 4 are conducted with spot-on formu lation s and 3 with either aerosol or spray formulations. In development of the 20 12 Res idential SOPs and today , it is we ll understood that the active ingredients in these liquid formulated products are more readily avai lable for transfer t o an individual than that of pet co ll ars which are des igned for slow release over time; however , at the time of the 20 12 SOP development, no residue transfer data we re available for use in recommendation of a default residue value spec ifi c fo r pet collar formulations. As a result, the use of th e default FAR 

### is expec ted to resu lt in a significant ove restimate of the risk from pet collar exposures. Along with th e non-ch e mical- spec ific pet collar transfer re sid ue s tudy , a number of hi gh end inputs define the asses s ment of exposure/risk to a pet collar treated pet , including the following:

• The app lication rates used in the assessment of the TCVP pet collars rep resents the maximum amount of ai in the entire collar. TCVP pet collar labels direct users to cu t off and dispose of any excess length once the product is fit and buckled into place. As described in the 2012 R

es id entia l Treated Pet SOP, th e rem ova l of excess length is anticipated; however , because the exact length cannot be determined , the correspond ing ai loss cannot be determined and exposure is assessed assuming the full collar length. The use of the maximum amount of ai in the pct

7 Davis , M., et al. Assessing lntermillcnt Pesticide Exposure from Flea Contro l Collars Conta inin g the Organophosphorus Insecticide Tetrachlorvinpho s . Journal of Expo s ure Science and Environmental Epidemiology

. (2008 ) 18 , 564-570. 8 Britton , W. Tetrachlorvinphos: Occupational and Residential Exposure Assessment for Registration Review. 0426984. 12/21 / 2015. 9 http ://www.epa .g ov / os a/human-studies-review-board 

### Page S of 14collar being assessed and the F AR tran sfer factor resu l ts in the potential fo r greater ex po s ure to th e indi vidual than if excess l e ng th were ass umed to have been r e mov ed

. • The Tre ate d P et S OP recommends dail y exposure duration s of 0.77 hours for adults and I hour for c hildren ( I to 4 years o ld ) based on s urvey data from w hi c h participants rep o rted the time s pent w ith an animal w hil e performing househo ld ac tiviti es. As de scrib ed in E PA 's respon se to N RD C's p e tition c la im #5 b e low, the SO P m ethod s used fo r assessmen t of adult a nd c hild postapp l ication r isks impl y continua l , v igorous contact occ urs w ith the treated pet during the en tire duration of exposu re. • The hi g hes t m ea n percent r esid ue transfe r of a lI three non-chemical- spec ific expos ure s tudie s ( i. e., the a mitr az st ud y) was se lec ted for th e asse ss ment of p ost

- application exposures from th e TCVP p e t co llar s . T he u se of these data result in th e hi g h est es tim ated ex po sures of a ll fo rmul ation

- specific expos ure data sources and , therefore , the m ost health protec ti ve estim ates of ri s k. Furth e r , pend ing H SRB rev iew, th e Davi s s tudy would be used as it result s in hi g he r mean pe rc en t residue tran sfer than th e a mit raz s tud y. 10 • As de fin ed in the T reated Pet SO P , exposure rate s resultin g from residue transf e r associat ed wi th a g iven formu lat ion and act ivity is a val ue, kn own as th e transfer coef fici e nt (TC). The dust a nd liquid TCs u sed to assess post-app li cation exposure to a d og treate d wi th th e TCVP collars we re derived from s tudies re presentin g ap plicator a nd g roo min g activ ities w i th dogs , respectivel y . Since th e applicators and groo m ers di rec tl y handled pe s ti c id e produ cts and co ndu cte d a ctiviti es that require d v igorous co nt act wi th the treate d do gs, it is expected that th e ir r es ultin g expos ures a re a re asonable app rox im ation of upper bound es timat es of ad ult and child contact w ith an an im a l treated wi th a p et co llar. In the ab se nce of direc t exposu re data for thi s sc enar io (e.g., hom eow ner activity w ith a treated p e t) , th e agency a ss ume s that th e applica ti o n a nd grooming activities are like ly to r esu lt in an estimate w hi c h is protective of indi v idual s petting, hu gg ing , or s leep in g w ith a T CV P-tre ated cat o r dog. 11
3. NRO C Argument: NRDC argues that EPA failed to con s ider th e Davis s tud y for th e est im a tion of po stapplication ri sks for ex po s ures to th e TCVP p c t collar. The Davis s tud y m easured h ow muc h TCV P tran sfe rred to people ' s h ands a ft e r five minutes of p e ttin g do gs wearing TCVP collars. NRDC argued that th e Davis s tudy wo uld yield ex po s ures w e ll above th e sa fe leve l dete nnin e d through E PA's exposure asse ss m ent of the pet collar formulation.
E PA R es pon s e : E P A con s ide red the potent ia l effec t of u s in g the D av i s study as the bas is for risk assess m e nt as discussed above in the respon se to NRDC A rgumen t #2. Formal use of the D av i s study is o n hold at thi s time pending a schedu l ed rev iew of it s possible use b y th e HSRB w hi ch i s sc hedu led in .January 20 1 6

. 12 T he refore, fo r purpo ses of the c urrent TCV P draft human health ri sk assessmen t in s up port of regi s trati on revi ew, OPP has u sed the Davis s tud y data to es tim ate preliminary, comparative po s t-applicati o n risks. EPA wo u ld rely on these data fo r reg ul atory

1 0 A sc ience review of the Davis study, as condu cted fo r H SRB rev iew , can be reference d at: W. Britton. Science Review of"Davis et a l. , 200 8. Assessi ng Intermittent P esticide Exposure from Flea Co ntrol Collars Con tainin g th e O r ga nopho s phorus In sec ti c id e Te trach lorv inph os" for HSR B Co ns iderati o n. 04 30707. 12/ 16 /20 15

. 11 http ://www

_ 2.e pa .gov ' pcst ic idc- scic ncc -and -asscss ing-pc s tic ictc-risk s/s tandard-op cra tin g-prrn.:cdurc s- rc s id cn l ia 1- pcst icide 12 hllp: "'' '' .epa.co\ o:.a human-:.tudics -rc \ ie\\ -board Page 6 of 14

### decision maki ng if H S RB dete rmin es that th e study is sc i e ntific a ll y valid and it m eets appropriate human ethics requirement s. The EPA review of th e app li cab le hum an e thic a l stand ards (as outlined in 40 CF R Part 26 

### Subpart Q) 

### ha s been cond ucted and it concluded that:

" there is no clear o r co nvi ncin g evide nce that th e conduct of th e D av is study was fundamentally unethical ; th at i s, the res ea rch was not intended to harm the participants and did not fail to obtain informed co n se nt. Similarly, th e conduct of the s tudy was not deficient re lative to th e et hic al sta ndard s preva ili n g at th e time the research was conducted; the stu dies did not place participants at increased risk of harm (based on knowledge available at th e tim e the study was conducted) or impair their informed consent." 13


### The ethics re v iew also states that:

" OPP wishes to re ly on the TCVP glove residue data generated. The data may be crucial to a potential E PA decision to improve public he a lth protect ion by imposing a more strin gent regulatory restr ict ion than co u ld be ju s tifi ed wi th o ut th e data. I f EPA proceeds under §26. 170 6, 

### EPA needs to obta in the views of the Hu man Studies Review Board , provide an opportunity for public comment, and publish a fu ll explanation of it s decision to re ly on th e data , including a thorough discussion of the ethic al deficiencies of the underl y ing research and the full rationale for finding th at EPA met the standard in 40 CFR §26. 1706 

### (c) (i.e. , that the research is essent i a l to a more str ingent reg ul atory action t o im prove protect io n of public h ealth )." The science review for the Davi s study1 4 

### has also been conducted and conc luded that the m e thod used t o collect tran sferab le TCYP r es idu es from petting/rubbing of the dogs trea t ed w ith T CV P pet collars is sc ientific a ll y valid. In addition to the tran sferable residue data , the Davis study also include s 1) plasma cholinesterase (ChE) from treated dogs 2) t-shirt samples collected from chi ldren exposed to TCYP tre at ed dogs in th eir r eside nces a nd 3) urin ary biomonitoring fo r adults an d child ren exposure to TCV P treated dogs in their residences. Fo r purpo se of the TCYP risk assessment , EPA o nl y would re ly on the transferable res idu e data as th ese data are the only e leme nt from th e study that resu lt in potentia ll y greater ri sks. The oth er st ud y elements are either not applicab le to human exposures (i.e., dog pla sma ChE measures) , or have sc ient ific limitations (i.e., a physiologica ll y based pharmacokinetic ( PBP K) model applicable to T CV P i s not ava il ab le to interpret the urin ary mon itorin g data). The EPA intends to present th e Davis study at th e next meeting of the H SRB which is sc hed uled fo r January 12-13, 20 16. 

### lf

### th e HSRB conc ludes that th e Dav is s tudy does not co ns titute a human s tud y and is sc ien tificall y va lid. then EPA can rely on these data for regulatory risk decision making. Alternatively , if H SRB concludes th e Davis study const itutes a human s tudy,

13 M. L y don. Ethics Review of Davis et al Research on Flea Collars with TCVP. l 2 / 15/ 2015.**~** W. Britton. Science Revi ew of"Davis et al., 200 8. Assess in g lntermillent P esticide Expos ure from Flea Co ntrol Collars Co ntainin g the Organophosphorus I nsect icide Tetrach lorvinphos" for HSRB Co ns ideration

. 043070 7. 12

/ 16 /20 15

. 

### Page 7 of 1 4th e n und er 40 CF R §26. 1706 , OPP i s require d to provide an o pportunity for publi c comment and publish a f ull explanat ion of it s decision to rely o n the ot herw ise unacc e ptable d a ta, includ ing a th o rou g h r ev iew of the e th ica l defic i encies of the underlyin g res earch and th e fu ll rationa le fo r finding th a t rel ian ce o n the data is cmcial to imp os in g a m o re s tringe nt regu latory restriction.
Unt il such time that th ese dat a h ave und e rgone H SRB re v iew , po s t- app li cat ion ri s k es tim ates for expos ures to pet collar treated pets are to be con s id e re d pre liminary a nd a re pre sente d for purpose of co mpari son only.
4. N RD C Arg um e nt : N RD C a r g u es th at E PA in co rrec tl y cons id e r ed th e TCVP p e t co ll ars to b e a liquid for mul ated produ c t, a s oppo se d to a s o lid formulation. N RDC s tates that the EPA " failed to rese arch th e TCYP flea co llar label ; instead it i gnored the in for mati on in the labe l ri g ht on the box r ega rdin g the che mical fo rmul ation [N RDC Opening Bri ef, p.67]. " The l abe l fo r th e H a rtz U ltraGu ard Fl ea and Tick Colla r fo r Dogs (EPA Reg. No. 2596 -84 ) s tates that " as the collar begi n s to work, a tin e wh ite p ow der will appear on the s urface." As a result, N RD C argu es that th e tran sfe r coefficient ( TC ) reco mm ended for so lid formulations should have be e n used in stead of the transfer coefficent fo r liquid fo rmul ation s as i s recomm e nded by the 2012 Resi denti a l SO P s . EPA R es pon se : Per EPA·s 2012 Res id e ntial SO P s : Treated P e ts , pet co llar products are categor ized as a li quid formulation. Thi s posit io n was based on r ese arch conducted a t the tim e of SOP deve lopment th at suppo rte d that pet collars fu nct ion by means of diffusion , transferrin g from th e co llar to the su rroundin g ar ea. More specifica ll y , th e ac ti v e in g red ient , which is e mb e dded in th e collar matrix , diffuses slow l y throu g h the matrix , thu s controlling th e amount of the active ingredi e nt at th e collar ' s s urfac e. The activ e in gred ie nt ava il able on the s urface of th e pet co ll a r the n " rub s off" o r transfers fr o m the co ll ar to the animal's h ai r coat v ia e mbedded lubr i cant s w hich function as transfer age nt s at the surface of the co ll ar. B ased o n th e categorizat io n of pet co llar s as I iqu id fo rmulati o n s, the assess m e nt of post-appli cation exposures fo r these product type s wo uld be co nducted with u se of the T Cs , an d the frac tion activ e ingred ie nt on th e hands fr o m TC stud ies (Fa ihand s ) reco mm e nd ed for th e assessmen t of liquid formulated products as rec o mm e nded in the 2012 Residential SO P s. 15
The information provided by NRDC s tates that th e labe l for th e Hart z UltraGuard Flea and Tick Collar for Dogs (EPA Re g. No. 2596

- 84) states that " as the co ll ar be gi n s to work , a fine wh it e powder will appear o n the s urface." H E D ha s confirmed th a t this s tatement i s prese nt on the c urrent labe lin g for the ide nti fied product and that an identi ca l s tatement is al so fou nd on th e follow in g TC VP pet co llar products (5 of9 total pet co ll ar produ cts): E PA Reg. Nos

. 2596-62 , 2596

- 63 , 2596 -8 3 , 2596 -8 4 , and 2596 -1 39

. Tak in g label sta teme nt s into accoun t , a nd ba sed upon furth e r researc h whic h s u ggests that s ome p e t co ll ars ma y act by ex trusion of th e activ e in g redi e nt fr o m th e co ll a r matri x as a fin e dust , H E D has reconsidered th e positi o n that the TCVP pet collars are a ll liqui d fo rmul ated produc t s. As a resul t o f this uncert ain t y, in the T CV P draft human health ri sk assess m e nt in s upport of r eg istration r ev iew , HED ha s upd ated the

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- reside111ialpcsticide Page 8 of 1 4assessmen t of post-application risks from TCVP pet collars in considerati o n of bo th th e dust- and liquid- spec ific TCs a nd Fai1rnnd s recomm e nded SOP va lues. 

### 5. NRDC Arg um ent: 

### NRDC arg u es t h at EPA underestimate s c hildre n 's exposures to their pets through u se of a n assumpt ion th a t toddler s s p e nd one hour per d ay with t h eir pets. NRDC a rg ues th at common sense and experie nce te ll them th at m a ny c hildren spe nd fa r more tim e with th e ir pets that one hour daily. N RD C addresses th e study used by EPA to determine the num be r of hours spent in daily contact w i th pets statin g that "a t le as t two of th e nine children in th e st ud y spe nt more than a n hour a nd a half a day w ith th e ir pet s eac h day , a nd at leas t one spe nt two ho ur s [NRDC Opening Brief , p.48]. " N RD C assert s th at E PA should use the uppe r portion of the distr ibuti on 

### (901h to 95 111 percentile) and assu me that children spe nd two ho urs per day with th e ir pets as was assumed in the 

### 2006 Rereg is tration E li g ibility D ec is i on (RED) for di c hl o r vos ( DDVP ).
EPA Re s ponse: In E PA 's 

### 20 I 4 residential assessment co nducted in re s pon se to NRDC's 

### 20 09 pet i tion to cance l all pet u ses of tetrachlorvinphos , EPA stated the follow ing regardi n g the daily exposure time assumed for post-applica ti on expos ures to TCVP treated pets:
"The expos ure t ime (ET) assumption u sed to assess res ide nti a l postappli cati on expo s ure to TCVP pet products is de ri ved fro m a stu d y (T san g and Klepeis , 

### 1996 ( 1 997 EPA Exposure Facto rs H andbook) ] w hi c h sought to evaluate the times that individuals spe nd p e rfo rmin g different activities around th e home. B ased upon th e 

### 20 12 Residential SOPs 1 6

, the p o int est i mates recom m ended for a dult and child ET with pets are 0.77 and I hou rs , respe c tively. "
In the study, a nim a l ca re i s defined as "ca re of household pets including activities with pets , play in g wi th the dog , wa lkin g the dog and car in g for pets of relatives, and friend s . " T he data identified the t ime s pent wi th an animal while p e r for ming household ac ti v itie s as r ecord ed in 24 ho ur diari es by study vo lunteer s . Whil e the activit ies defin e d do not n ecess aril y rep rese nt th e time vo lunteers were acti vely engaged in constant contact with the an im al as i s implicit in th e pos t- application dermal and incidental oral algorithms, the data are the most accurate represe nt a ti o n of tim e s pent with p e t s avai lab l e a nd , th e refore , it is assumed th at co ntact i s co ntinual thro u ghou t the timed ac tivity. The agency ass um es the ET va lu e (adult , 0.77 hour s; ch il dren , 

### 1 hour) reflects a reasonable hi g h end est im a te of ti m e spe nt in co ntac t w ith a dog treated with T CVP pet products.
When u se of the s tud y data are coup l ed with hi g h end assump ti ons of p et co nt act , the result is an expos ure assessment that inhere ntly imp li es v i gorous, continual co ntact for the en tire duration of co ntact. While it is poss ible th at an a dult o r child may be in c l ose contact with a p e t intermitte ntl y thro u gho ut the day, the y wo uld not be activ e ly e n gaged in the hi g hl y v i goro u s contact implied b y use of the TCs based on the app li cato r ex p osure data for the full expos ure duration assu m ed. Furt he r, it is possible that adults or children may be ex posed fro m sleep in g

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. NRDC asserts " th at common sense and experience te ll them that many children spend far more time with their pets that one hour daily (NRDC Opening Brief , pp. 47-48]." It must be emphas ized th at w hen an adult or child · ' spe nds time " with a pet, it is unlikely that the entirety of this time is spent engaged in vigorous, co ntinual contact during thi s e ntire period as is implied by the inputs and methods used in the 2012 R esi dential SOPs to ca lcu late exposures from contact with treated pets. As described above, the study \· vh ich supports th e exposure time inputs for the 2012 Residential SOPs: Treated Pets is based on measures of time spent in " animal care " where animal care is defined as "care of household pets including activities with pets, playing with th e dog , walk in g th e dog and caring for pets of re lati ves, and friends. " It is c ri t ical to understand the connection between time spent in animal care and SOP expos ure time inputs which inherently implies continual , vigorous contact during the entire exposure duration. As defined, animal care could imply direct vigorous contact with a treated pet for a limited period of time, but could just as likel y have involved activities which required littl e to no contact of the pet while it was be in g cared for.
The assump ti on of vigorous , continual con tact is based upon the algorithm used to estimate postapplication dermal and incidental oral exposures from contact with treate d pets. Of the input s used , the du s t and li quid T Cs we r e deriv ed from studies representin g applicator and grooming activities with dogs , respectively. Since the applicators and groomers directly handled pesticide products and conducted activities that required continual , vigorous co ntact with the treated dogs , it is expected that their resulting exposures are a reasonable approximation of upper bound estimates of adu lt and child contact with a treated an im al. In the absence of direct exposure data for thi s scenario (e.g. , hom eowne r activity w ith a treated pet), the agency assumes that the application and grooming activities are likely to resu lt in an estimate wh ich is protective of individuals petting , hugging , or sleeping with a TCVP-treated cat or dog. Further, EPA sup ports the u se of mean values fo r default inputs , including th e expos ure time input. 1 7 When the default valu es are considered together in the exposure algorithm, the combinat ion of these inputs result in upper percentile exposure es tim ates
. 

### If EPA we re to assume an upper percentile for all inputs (e.g., 90th to 95t h percentile), the result would be exposure estima te s that are overly conservative and unrea listic ; particularly given the already health protective nature of the assessment methods and inputs

. NRDC identified a prior EPA pet assessment conduc ted for the DDVP RED which used a daily exposure time assu mption of 2 hours. This assessment was conducted in 2006, prior to rele ase of the updated 20 12 Residential SOPs. At that time , resid e ntial exposures were assessed bas e d on the recommendations of the 1 997 Standard Operating Procedures (SO P s) for Residential Exposure Assessments

. In this outdated document , an exposure time of 2 h ours per day was recommended based on, '·the best professional judgement and experience of the OPP staff. T he t imeframe (2 hour s) is approximately the sa me t ime ch il dren play outside per day. Thi s i s

17 hllp. '' ""'' 2.epa.gov**pcsticide-.,cience-and-a~scc;sing,-pesticide-ri!>ks** standard-opcrating,-proccdures-residentialpl.'st1cidc Page 10 of14assumed to be an upper-percentile value." EPA contends that the recomme ndation s of the 2012 Residential SOPs are based on the best data available regarding time spent w ith pets and that the one hour exposure tim e recommendation is a health protective input for determination of high

level , continual contact with treated pets. 

### 6. N RDC Argument: 

### NRDC argues that E PA failed to account for an established route of exposure, toddlers who touch an object or food with pesticide-contamin a ted hand s, and then put that object or food into hi s/ her mouth (or " indirect hand to mouth activity"), rai se d by 

### NRDC in it s petition. NROC argues that published s tudies s how that " there is actually notic eable indirect hand to mouth activity in infants and children [NRDC Opening Brief, p.50]," and argues that ·'one study found that , on average, a toddler will touch an object a nd then put that object into his or her mouth 15 times in one hour [NRDC Opening Brief , p.50]." NRDC acknow ledges that EPA· s 2012 Residential SOPs recognize that ora l exposures consist generally of two pathways, children contacting treated surfaces and putting their hand s in th e ir mouth and from putting objects or other toys in their mouth that had been in contact with treated surfaces. EPA did not conduct an as s essment of indirect oral exposures ( i.e ., object

- to

- mouth) in its 2014 residential assessment and instead exp lain ed , "the quantificat ion of hand-to-mouth expos ures fo ll owing direct contact with the treated surface always results in exposures of a greater m agnitude and , as a result , a more health protective assessment of ri sk

... than from indirect object-to-mouth exposures . "
EPA Re s pon se: The 20 12 Residential SO Ps describe that residential po s t- application exposures may occur through dermal , inhalation , and / or incidental oral (non-dietary in gesti o n) routes. Post

application dermal exposure can occur from surface

- to-skin residue transfer for individuals contacting treated surfaces. P ost-application inha lation expos ure can occur from concentrat ions of pe s ticide active in gred ient remaining in the ai r fo ll owing treatment. Finally , post-application oral exposures are based on the ingestion of pesticide re sidues that can result from transfer of residues from hand-t o-mouth , object-to-mo uth , or via direct ingestion of res idue s throu gh so il ingestion, dust ingestion , or ingestion of pesticide granules or baits. The assessment of objec t- to

mouth exposures are recommended only for treated turf and treated carpets/ hard floors as it is on ly from these s urfaces th at seco ndary exposures are expected following contact with the treated su rface. The methods used for determinat ion of pesticide residues availab le for postapplicat ion dermal and oral exposures from res idential pesticides are described in th e 2012 Resident ia l SO Ps . 18
NRDC acknowledges that EPA 's 20 l 2 Residential SOPs recogni ze that oral exposures consist ge n era ll y of two pathways, hand-to-m outh and objec t-to -mouth exposures. However, NRDC argue s that I ) E P A should account for object

- to-mouth exposures from objects whic h have come into contact with a T CYP treated pet and then mouthed by the child and 2) E PA sho uld a lso account for " indirect hand-to-mouth" exposures whereby c hildren touch an object or food with pesticide-contaminated hands , and then put that object or food into his/her mouth.

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### 14In response to the fir s t argum e nt , EPA described in the 20 14 re s p o n se to the NRDC pet it io n that , "with use of the methods described in the indoor env ironments and lawn/turf SOPs , the quantification of hand-to-mouth exposures following di rect contact with the treated su rfa ce a lways results in exposures of a g re a ter m agni tude and, as a re s ult , a more health pro tectiv e assessment of risk ( i .e., a lower M O E) than from indirect object-to-mouth exposures." NRDC asserts th at because,

.. it (objec t-to - mouth exposure) would share a co mm on toxico l og ical e ndp o int , th e object-to- mouth ex posure would be combined with the derma l and hand-to-m o uth exposures. " To clarify , w h e n quantifi ed, the g reate r magnitude of h and-to-mouth to object-tomouth exposu res is such that the ad diti on of objec t

- to-mouth exposure would have little to no impact on the combined risk s. When h a nd-to-mouth and object-to-mouth ri s ks are compared for turf , the resulting diff e rence is a - 

### 30 fo ld difference and, fo r ind oor e nviro nm en t s , the difference is

- 4 to 7 fold for hard surfaces and ca rpet, respectively. Further, E PA policy recommends that incidental oral ex po s ure sce nario s (i

. e . , hand-to-mou th and objec t-to-mouth) shou ld be co n sidered inter-related and it is lik ely th at th ey occur inte rs p ersed am ongst eac h other across time. Combining these sce n arios with th e derm al exposure sce nari o wou ld be ove rl yconservative because of the conse rvative nature of each ind ividual assess m e nt. Therefore, the post-app li cat ion exposure scenarios which s h ou ld be combi ned fo r c hildren 

### I < 

### 2 year s o ld are the dermal and hand

- to-mouth sce nari os o nl y . This combination is considered a protective estimate of children's ex po s u r e. Therefo r e, in th e case of the p os t -application assessment of TCVP w hi ch has been determined to have n o dermal hazard, it is most appropriate to present th e h and-to- m outh and object -to-mout h exposu r es separately. Regarding 

### N RDC's second argume nt, the assessme nt of hand

- to-mouth ac ti v ity as conduc ted with use of the 20 1 2 Residential S OP s accou nt s fo r the " indirect hand-to-mouth " ex p osu r es d esc rib e d fro m ch il d re n touching a n objec t or foo d with p esticid e-co ntaminated h a nd s, and then putting that object or food into his/ her mouth

. Jn ord e r for the pesticide residues to have bee n transferred to an object o r food from pesticide-contaminated hands wou ld first require tra n sfer of re s idu es from a treated s urfac e to th e h a nds. If E PA w e re to attempt to assess an " indire ct" exposure, a mass/balance m easure would h ave to be undertaken th at would require removal of the re sid ues determined to be on the hands to the objec t or food ite m h and led, thus s ub trac tin g from the to ta l o n th e h a nds. Th e refo re, th e quantificati on of combined o ra l ri s k s from "i ndirec t hand-to-mouth '

. and ''d irect h and-to -mouth" o ral exposures wo ul d be , in effect, add ing back those indirect oral exposures which were subtracted resulting in the same o utcome h ad the indirec t exposure never been ca lculated.


### 7. NRD C A r g um e n t: NRD C arg u es t h at EPA 's a l go rithm fo r c alcul a tin g th e amoun t o f " tr ansfe r a bl e r esi du e" is in co n s is t e nt w ith th e findin gs o f th e D av i s s tu dy w hi c h found th a t th e r es idu es wer e co n ce n trate d at t h e n eck of t h e an im a l fo ll o win g a ppli ca ti o n . NRDC argue s th at w he n ca lcu lat in g th e res idu es a v a il able to tran sfe r from th e su r face of a treated pet to an exposed indi vid ual , EPA ' s dermal a lgorithm divides the residues ava il able to transfer by th e su rface area 

### of th e treated a nimal. 

### In th e Davis study, researc he rs found that res idu es we re concentrated a t the nec k , an d that very low levels of residue were fo und at th e ta il. Therefore, regardless of pet size , the bulk of the exposure is from con tact wi th the neck.

Page 12 of 14

### EPA Re s po n s e: The algo ri thm for quan tifi cat io n of dermal ex p osu r es from the 

### 20 1 2 Residential SOPs : Treated Pets ca lculates transferable res idues, or those residues an ticipated to transfer from the surface of the treated anima l to the exposed indiv idual , b y m eans o f mu lti plying the maximum appl ication rate of the product app lied by the fraction of the application ra te anticipated to be availab l e for tr a n sfe r (as determined by means of residue tran sfer " petting " studi es) and the n dividing by su rface area of the treate d anima l. The design of th e algorithm to account for th e surface area of the treated animal was intentional.
Contact with a treated pet is not expected to be limited to one a rea of the pet , particularly w hen these exposures are ant icipated to be v igoro us and continual for up to o ne hour daily. To assess exposures as propo sed by NRDC would be equ ivalent to an adult or ch il d havin g a high level of co ntinu o u s con tact w ith o nl y the neck of the ir p et for a full ho ur dail y, w h ich is h ig hly unli kely

. Durin g this period of expos ure, i t is just as likely , if not more likely , that contact with a treated animal wou ld occur elsewhere on th e animal's body (e

. g. , along the back, belly, chest, and ribcage ) as it wou ld the neck.
The majority of pet product fo rmulation s are not applied in a manner whic h would limit the concent rati o n of residues to one area of the pet ' s body. For exa mple , an application of a s hampoo , l iq uid sp ray, or dust / powder wo uld typ ica ll y be app li e d to th e ent irety of th e a nim a l 's body. In th e case of pet spot-on products , w hil e the initial applicat io n may be isol a ted , pet residue transfe r studies show that wit hi n hours of application residues begin to sp re ad over the s urface a rea of the animal. Jn th e case of the Davis study, only the neck (over th e co ll ar and under the co ll ar) and tail mea s ures were collected. In accordance with N RD C's claim, the se residues were concentrated to a larger degree around the neck vers u s the tail. H owever, it is important to note th at the Davis stu d y researchers limited th eir sampling (petting) to only these areas of the dogs ' bodies. H ad the r esearche rs collecte d samp les from o th er p arts of the d ogs ' bodies, s u c h as the back or along the r i bcage, they may hav e found re s idues to have spread to other areas of the body as well an d it is possib le that th ese could be in excess of th ose found on the tail. Further, as evidenced by the Davis study resu l ts , mea s urable res idues were present on the tail of th e animals , thus indi ca tin g that the r esidues are sp r ead ing ove r th e a nim a l and n ot , as suggested by N RD C, concentrated so lely around the neck area.
In conclusion, an exposure assessme nt which assumes a ll expos ure s we r e iso lated to o ne area of the an im a l 's body and that a ll con tact fo r the entire duration of expos ure were to occ ur to thi s area of the body on ly is unrealistic. For the majori ty of pet product form ulation s, it is more likely that residues a re distributed over the e ntire p e t surface area and that a n adul t o r child 's co ntact w ith the pet i s n o t limited to one a rea for th e e ntire duration of ex posure. For p et co ll ar formulat ions, whil e the residue s may potentially be concentrated around the neck area, it is unlikely that the adult or child contacting the treate d pet would o nly contact this area. He or she wou ld lik e ly also contact othe r areas of the body, w hi c h , ba se d o n the D avis study, wo uld have l ess r es idu e to be transfe r red ( th e D av is s tud y residue measures from th e tail were we ll bel ow those measured around the neck) , thus reducing overall exposures from these areas alone. In effect, if exposures were estimated assuming a greater concentration about the neck , the exposed individual wo uld be ex posed more hi g hl y w hen co nt act in g the nec k area a nd less so when

Page 1 3 of 1 4

### co ntac tin g o th er areas of the pet , thu s havi ng an effec t approximately equ ivalent to the curre nt design th at assumes th e r es idu es are di s tributed across the e ntire surfac e area of the ani mal.

P

age 14 of 14