### UN I TE D STATES EN VIRO N M ENTAL PRO TECT IO N AGENCY W AS HI NGT O N, D .C. 2 04 6 0
O F FI CE O F C H E MI CAL SAFE T Y AN D P OL L UTI ON PR EVEN TI ON 

### MEM ORAN D UM D ATE: March 14, 2016 SU B JECT: B romadiolon e. Human Health Seeping Docume n t in Support of Reg i strati on Rev i ew .

PC C od e : 112001 D ec i s ion No .: DP B a rc o d e: D429382 R eg i s tr a tion No .: NA Pe titi o n N o .: NA Re g ul a t ory Acti o n : Reg i stration Rev iew Cas e N o . : Ri s k Assess m e nt T y p e: Seeping D ocume nt TX R N o .: NA CAS N o .: 28772

- 56

- 7 40 CF R : NA M RID N o. : NA F ROM: Laura No ll en , Bio l ogist

# e/~**./ j/-**  

# /--- Myron S. Ottley , Senior Bio log i st

# ~ Risk Assessment Branch III (RAB3) Hea lth Effects Divis i on (7509P) 

### TH RO UG H: Margarita Collantes , Bio l og ist

# -lll**~** Jaime D ' Agostino , P h. D
. , Toxico l og i st .// Hea lth Effects Division (7509P) Chri_stine_**Olinge~ ,**  

### Branch Chief, /)/ /
. . //
_ Registration Actio n Branch 3 

# {_U j;?L- L .-- Health Effects Div i sion (7509P) T O : Ricardo J ones, Chemical Review Manager Melissa Grab le, Team Leader Risk Management and Imp lementation Branch 1 (RMIB 1) Pesticide Re-Eva l uation Division (PRD) (7508P) As part of Reg i strati on Review , the Pesticide R eevaluat ion Division (PRD) has requested that the Health Effects D ivision (HED) provide a human health risk assessment seeping doc u ment for the rodenticide, bromad iolone
. The most recent HED assessment for bromad iolone i s t he HED Chapter of the Rereg i stration El ig i bility Decision (RE D ) and the RED addendum that were completed in 1995 and 1996 , respectively (J. Redden , 9 / 2711995; J. 

### Redden , 4/ 4/ 1996).

Page 1 of 31

### Executive Summary Following is the H ea lth Effects Division's ( l-I ED's) human health scoping document t o support Registration Rev iew for the rodentic ide bromadiolone, 21-1-1-Benzopy ran-2-one , 3-[3

- (4'- bromo[I, I '-biphenyl]-4-y l)

- 3-hydroxy -1-ph eny lprop y l]-4-hydrox y-. T o evalua te the scope of work necessary to support Registration Review , HED has considered previous risk assessments for bromadiolone ; updates to its toxicity, expo s ure and usage databases; and the latest Agency science policy and ri sk assessment methodologies. Br omad iolone is a second generation anticoagulant rodenticide which inhibits coagulation synthesis, resulting in bleeding and eventual death in target pests, such as rats and m i ce . This mechanism of action has been estab li shed in humans. Bromad io lone is re g i ste red to contro l Norway rats (including warfar in-resistant rats), roof rat s and house mice and is fonnulated into numerous baits in ready-to use ( RT U) p l ace packs, blocks, chunks, paraffin pellets, traditional meals, cakes , slabs and pastes. All end-use products for bromadiolone contain 0.005% active ingredient (a i) by weight and are intended for occupat ional/ professional use only. For al l second-generation anti-coagulant rodenticides, cons um e r-u se products (i.e.,**products~** 

### 1 lb) contain i ng bromadiolone are prohibited. Professional / commercial uses of second-generation anticoagulants requ ire bait stations for all outdoor and above-ground placements and for indoor placements where children, wild li fe or domestic animals may be exposed
. Furthe rm o re, labels prohib it broadcast applicat i o n of pe ll et baits. Bromadio lone is marketed in a minimum of 8 pound ( lb ) unit s for use in and around agr icultw-al buildings and a minimum of 16 lb units for u se in and around industriaVcommercial/ residential buildings (ships , trains , aircraft, homes or temporary residences, related port/terminal buildings. trash receptacles , food processing faci l ities or sewe r s)
. Bromadiolone restricts app li cation within 50 to 100 feet of man-made structures , depending on the end-use product. All labels require that handler s wea r shoes plus socks and g lo ves, at a m inimum, and wear waterproof g loves when retrieving unused bait or when disposing of rodent ca rcasses. The bromadiolone toxicology database is not cons idered adequate for ri sk assessment of the currentl y -r egiste r ed bromadiolone formulations and use patterns. Spec ifi ca ll y , subchronic dermal and inhalation stud ies are needed to address the potential toxicity following occupational dermal and inhalation exposures. l n 

### addition , the Revised Part 158 Data R equ iremen t s ca ll for the following stud ies t o be included in the toxicit y database: acute and subchronic neurotoxicity , reproduction and fertility , and immunotoxicity. H oweve r , the requ irements for these studies have been waived (TXR0057326). The primar y toxicity r esu lting fTom bromadiolone expos ure i s hemorrha ge in man y interna l organs s uch as the sp leen , kidney, lung s , gas tro int est inal (G I) tract; and ex te rnal b leeding through the nose, vagina and nail beds. Effects included death, and were observed in rats , dogs and/or rabbits.

Pa ge 2 of 31

### The Reregistration Eligibility Decision document (RED) for bromadiolone did not quantify dietary (f ood and drinking water) exposures because of the limited use pattern (strictly non-food rodenticide use with no dietary exposure). As part of Registration Review , the toxicity endpo int s, Points of Departure (PODs), and uncertainty facto r s (U Fs) will be re-evaluated for bromadiolone according to cunent HED approaches in hazard character ization. Residentia l adult handler exposures and post-application exposures to adults or children are not expected , as bromadiolone consumer- based products are prohibited and any uses with the potentia l for residential or child access (e.g., above-ground uses or around res idential areas) require the use of tamper-resistant bait stations. Therefore , residential handler and postapplication exposures will not be assessed during Registration Review. Residential bystander exposures resulting from off

- site transport (i
. e., spray drift or vo lati li zation) are not anticipated , due to the registered formulations of bromadiolone. Occupational handlers may be exposed via th e dermal and inhalation routes from the registered uses of bromadiolone as they fill/refill bait stations or distribute bromadiolone bait products into rodent burrows or sewers. Shor1-term dermal and inha lation occupational handler exposure assessments are expected during Registration Review based on the potential exposure to handlers (loaders, applicators) during the application of pelleted , meal bait or paste formu lations of bromadiolone. Exposure to other bromadiolone products formulated as RTU baits, cakes , blocks , or other wax/paraffin-based formulations are considered to result in negligible exposures . Occupational post-application exposure is not expected from bromadiolone reg i stered use patterns. At the t ime of Registration Review and based upon the reevaluation of toxicity endpo ints , POD s , and uncertainty factors, HED w ill determine the specific appropriate occupational handler exposure risk assessments to conduct for bromadiolone. Introduction Bromadiolone, a coumarin , is a second

- generation anticoagulant rodenticide. It 

### is fonnulated into numerous bait formulations such as RTU place packs , blocks, bulk paraffin pellets , cakes , pastes and meal baits (e.g., EPA Reg. Nos. 270-372 and 12455-34). Bromadiolone end-use products contain 0
. 005% ai by weight, and labeled target pests are Norway rats (including warfarin-resistant), roof rats and house mice. Registered bromadiolone use sites include in and within 50 to 100 feet of h omes and other permanent or temporary residences , food processing facil iti es, industrial and commercial buildings, trash receptacles , agricultural and public buildings , transport vehicles (ships, trains), docks and other port oftern1inal buildings and related structures associated with these sites. Some products also allow sewer treatments , as well as rodent burrow baiting. Bromadiolone application rates are typically highest for rats, w ith calculated single maximum rates per treatment location around 5.0 x 10-5 

### lb ai. Al l end -u se products prohibit broadcasting bromadiolone or applying products directly to food or feed crops. The most recent HED assessments for bromadio lone are the HED Chapter of the RED Document and the subsequent addendum completed in 1995 and 1996, respectively 

### (J. Redden , 9/ 27 / 1995)(1. Redden , 4/ 4/ 1 996)
. Page 3 of 31

### ln 2008, the Agency issued a risk mitigation decision for ten rodenticid es , of which bromadiolone was included. The mitigation decision se t restriction s in order to minimize exposure to chi ldren , non-target wildlife and domestic animals
. The risk mitigation decision does not app ly to rodenticide fi e ld ( non-commen sa l rode nts) uses or tracking powder prod u cts ; however , bromadiolone i s not registered to control non-commensal rodents , and there are no tracking powder products for the ai. The following is a summary of the 2008 mitigation that applies to second-generation anticoagu lants, includin g bromadiolone:

• Consumer-based products**(~** 

### 1 lb.): 

### o Consumer-based products for second-generation anticoagulants , including bromadiolon e, are prohibited. • Professional-based products o Must be so ld in quantities**of ~**  

### 8 lb s. for seco nd

- generation ant icoagu lant agricultural building use**and ~**  

### 16 lbs. for second ge n eration anticoagulants ; above ground outdoor use). o 

### May not be offered for sale in consumer stores (e .g. , hardware. grocery , etc.). o Must also be placed within I 

### 00 feet of a s tructure (fence and perimeter baiting beyond I 

### 00 feet of a man-made structu re are prohibited) when used outdoors and above ground , see 

### 50 foot Document Clarification Leffer to Bell (03. 20.12) (signed) in docket number E PA-HQ-OPP -2006-0955

- 0820 found at www.regu lations.gov
. o 

### For use s of seco nd-generation anticoagulants, labels require bait stat ions for all outdoors above grounds placements and /or indoor placements where children, wi ldlif e or domestic animals may be exposed. Loose baits/ pellets / meal as 

### a form for above ground outdoor uses are prohibited. R egistered end-use products containing bromadiolone are intended for occupational use only and must comply with the 2008 tisk mitigation measures, as outlined above. Following review of all active reg i strations for bromadiolone, a ll end-use products appear to adhere to these mitigation stipu l ations. Refer to Table A.l., 

### Use Profil e for Bromadio lone (Attachment 1 ), 

### for m ore information on the current registTations , including maximum use rates and methods of app lication for bromadiolone products. Refer to Attachment 2 (Tab le A.2.) for the chemical identity and Attachment 

### 3 (Table A.3) for the physiochemical properties of bromadiolone. 

### Ha z a rd ld e nti fica t io nffox ic ol ogy The toxicity database for bromadio l one consists of an ora l 20-day study in rat s, a 90

- day oral study in dogs , prenatal developmental toxicit y stu die s in rats and rabbits a nd a 

### mutagenicity battery. Bromadiolone is a potent anticoagulant , causing a disturbance of clotting factors in the blood , and targeting multiple organ systems at the microgram (Jlg/kg) level in laboratory mammals. Observed effects were death and external bleeding (b lood y urine and stoo l s , vaginal , nasal and
Pa ge 4 

### of 3 1

### nail bed bleeding ) in rats , dogs or rabbit s , and bleeding in internal o rgans (liver, G I tract kidneys spleen liver, thyroid , sk in) in rat s and/or dog s. Jn addition , clinical signs s uc h as hypothermia, respiratory difficulti es , pale mucosa, drowsin ess and atonia were seen in do gs; and hypotonicity a nd pale eyes were observed in rats . I ncreas e d prothrombin ti me wa s seen in dogs. Increased death was observed at th e hi g h-dose le vel in do gs a nd at multiple dose lev e l s in rats. The ava ilable to xic it y data d o not indicate a concern fo r neurotoxicit y , immunotoxicity or mutagenicity. No carcinogenicity s tudie s we re co ndu cted , as lon g -t erm exposu res are not a nti cipa ted for this non-food use c hemical. The prenatal developmental st udi es in rats and rabbit s do not indicate a concern for e ither toxicity or suscep tibili ty in the offsprin g. HED h as detennined the dennal absorption u si n g a weight of the evidence approach considering the cuiTentl y availabl e data. The phys icochemical properties of bromadiolon e (mo l ec ular we i ght of 527.41 g / mol and lo g 

## Kow of 4.3) support a low d e rmal absorption. Furthe rm ore, u s ing the Na ti o nal Institut e for Occupational Health and Safety (N IOSH) fin it e do se s kin permeation calculator (http : //www . cdc
. gov/ nio s h/topic s / s ki n/ finit eS kinPerm C al c . html ) and th e phy s ical chemica l properti es ofb ro m ad iolo ne (see Ap p endix 3a for a full list) , a predi cte d dermal absorpt ion factor of 0.08% was obt ained over an 8 hour period w ith a derma l load of 0.0872 )..lg/ cm 2 

### (see Appendix 3b fo r ca lculation s). Th e derma l l oad of 0.0872 )..lg/cm 2 

### was de ri ved by taking the expected d ai ly expos ure ( 95. 9 )..lg) and dividing by the entire su rf ace area of the hand s 

### (
- II 00 cm2 ). 

### The Finite Do se Skin Permeation Ca lcu lator was dev e loped through s upport of a Ce nt e r of Diseas e Contro l /National In stitu te fo r Occ up ational Safety and H ea lth (CDC/NIOSH) grant , and provide s an es timation of fluxes , skin concentrations, and amo unts a bsorbed from a n y s ize d ose applied to partially or fully hydrated sk in , u s in g the phy s icochemical properties of the tes t co mpound and defined expos ure parameters (Kas tin g , G.B. 2006; Wang , T.F. 2007; Ka st in g , G.B. 200 8 ; M ill er , M.A. 2010). Currently , OPP does n o t rel y on (Q)SAR m ode ling alone t o derive a D ermal Abso rption Facto r ( DAF ) for ri s k assessmen t. However, est im ates from the Finite Dose Skin Permeation Calcu lator ma y be u sed w ith read -across data to support a weight of the ev id e nce evaluation. In add ition , the E urop ea n Com mi ss ion's Sta ndin g Co mmittee on B ioc idal Product s , as part of their evaluation ofbromadiolone in 2010 , determined dermal abso rpti on va lue s of 1.6 % in an 

### in vitro human s tud y . Based on a weight of the ev id e nce app roach , the d e rmal absorption ofbromadiolone i s likely less than 10 %; howe ve r , HED chose a dermal absorption va lu e of I 0% as a conservati ve estimate based on the ava il able data. The ava ilable pharmacokinetics data s how bromadiolone is distributed to the li ver w here it accumulates ( li ver T 112 

## = 17 t o 318 days in a biphasic expone n tial patt ern). The study did not p rovide further in fonnat ion on the absorption , distribution , metabolism o r exc r etion of bromadio lone. Br o madiolone ha s high ac ute tox icity (To xic it y Ca tego ry 

### T) v ia the oral , d e rmal and inhalation routes. It causes minim a l irritation by the d e rm a l (Tox icit y Category IV) and ocu l ar (Toxicity Category Ill ) routes. No data are available on dermal se n s iti za tion Please refer to Attachment 4 fo r the summary of the toxicity endpoints and PODs and Attachment 5 for the comp lete t oxicity profile t able for bromadiolone.
Pag e 5 of3 1

### The available toxicity databases were evaluated for severa l second -generati on rodenticides, including bromadiolone. The Hazard and Science Policy Counc il (HASPOC) determined that the followin g s tudies were not required for bromadiolone , as they were not expected to provide a lower POD for risk assessment:
• 870.3800, Reproduction and fertility effects • 870.6200a, Acute neurotoxicity • 870.6200b , Subchronic neurotoxicity • 870.7800 , Jmmunotoxicity
Conclusions: The toxico logy database i s n o t ade qua te for risk assessment of the current registered formulations and use patterns for bromadiolone. Specifically , subchronic inhalation and dermal studies are required to address the potential toxicity following occupational inhalation or dermal exposu re , respectively. In addition, the required (CFR Part 158) acute and subchronic neurotoxicity stud ie s, a reproduction and fertility effects study and an immunotoxicity study have not been s ubmitted. H owever, th ese stud ies are not expected to provide a lowe r POD ; therefo re, they are not required (TXR No. 0057384 , 03/0 1 /2 015 , U. Habiba ). While a subchronic inhalation study is required for bromadiolone , the addition of a PF- 5 respirator to all active regi s trations for the chemical may mitigate potential inhalat ion exposure s to a point where the margin s of exposure (MOEs) based on the HASPOC sc ree nin g criteria would no lon ger be of conce rn. Based on the low MOEs calculated for dermal expos ure , label mitigation will not b e a potential option to mitigate for dermal exposures and risks at this time. As part of Registration R eview, the toxicity endpoints , POD s and uncertainty factors wi ll be re-evaluated according to current HED approac he s in hazard characterization. 

### R es idu e C he mi s t ry a nd Di etary Ex p os u re All u ses of bromadiolone a r e classified as non-food uses ; therefore , no tolerances are established or needed. I n addition , a dietary exposure assessment to bromadiolone from food is not needed , as all end-use products prohibit broadcasting bromadiolone or applying product s directly to food or feed crops. The registered use patterns for bromadio lone are also not expected to result in dietar y exposures to adults or children from surface or ground drinking water. Conclusions A dietary exposure assessment is not anticipated to be needed during Registration Re view. 

### R esi d e nti a l Ex p os ure R es id entia l Handlers Bromadi olone-con tainin g products are intended for occupational use only. Cons umer- based products for second

- gene r ation anticoagulants , including bromadiolone , are prohibited
. Th erefore , residential handler exposures are not expected.
Page 6 of3 1

### Residential Post-Application Tamper resistant bait stations are required for any bait placed above ground or w here children, pets or non-target wildlife may be present or have access. Post-application exposw·es to bromadiolone product s placed in tamper-res i stant bait stations or below ground are not anticipated. Therefore , a residential post-application exposure assessment is not a n tic ipated in order to conclude with reasonable certainty that re s idential exposures to bromad io lone do not po se a significant human health risk.

on-Occ upational Sprav Drift or Volatilization Since bromadio l one i s applied as a solid formulation by hand, largely in tamper-resistant bait statio ns, neither exposure from drift or volatilization i s expected. Conclus i ons Re s idential exposure s are not expected. Therefore , a residentia l hand l er o r post-appl ication assessment is not required during Registration Revi ew. Given the formulations and registered uses, the Agency does not expect exposures from sp ra y drift or volatilization. 

### Agg r ega te Ri s k Assessme n t In accordance with the Food Quality Protection Act, HED must consider and aggregate pesticide expos ures and risks from three major sources: food , drinking water and re s idential exposures. For bromadiolone, there are no dietary food exposu r es. Broadcast applications of bromadiolone and direct app l ication s to food or feed crops are prohibited. Additiona ll y, bromadio lone products are not intended for consumer use, and any above-ground uses of bromadiolone where children may be exposed must be in tamper-resistant bait s tation s. Based on the regi s t e red uses , HED does not anticipate dietary (food or drinking water) or re side ntial exposures. Therefore, an aggrega te risk assessment is not anticipated for children or adults based on the current bromadiolone use pattern and formulations. Co nclusions During Registration Rev iew, an aggregate r i sk assessme nt is not requ ired fo r c hil dren or adults based on the current bromadiolone use pattems and formu lations. 

### Occ up at ion a l a nd Co mm ercia l E xpo s u re Occupational/Commercial Handler Exposure Handler exposures have not previously been quantitatively assessed for bromadiolone. Handlers may potentially be exposed by the dermal or inhalation routes in the short-tenn duration of ex posure from: (1) placin g pelleted, meal or pa s te bait f01mulations in burrows; (2) loading bait s tatio n s w ith meal bait or bait pellets f r om larger containers; and (3) secu r ing lar ge p araffin blocks at bait stations in sewers. It 

### is unclear from lab e l s a nd other available information the extent to which it is necessary , due to size o r design of packages , for handlers to directly handle or contact bait during bait station loading , which may re s ult in dermal exposures; or th e extent to which it i s po ssib le for inhalation exposures to occur following contact with meal baits or pellets durin g bait s tation loading. Page 7 of3 1

### Occupational handler dermal and inhalation expos ures from load ing or applying ba it block s, cakes , s l abs or other RTU formulations (e.g. , placement packs ) are considered to be negligible. Due to the nature of the re g istered use patt e rns , long

- term occupational exposure is not expected. End -u se product labels require handlers to wear gloves plus shoes and socks at a minimum when app lying bromadiolone , and waterproof gloves when handling used bait or rod e nt carcasses. Most label s also requi re handlers to wear long - s leeved s hirt s and long pants. The 1995 H ED RED chapter did not establish a POD to estimate occupational handler risks. Therefore , HED recomm e nd s using the m a terna l no-observed-adverse-effect leve l (N OAEL ) of 0.004 mg!k g / day from th e rabbit prenatal developmental toxicity study mat e rnal based on an increased in cidence of vag inal bleeding at the maternallowe s t-observed-advcrse -effect level (LOAEL) of0.008 mg/kg/ day. During Regi s tration Revi ew, the Agency will conduct a revised handl e r ex posure assessment s using updated policies and body weight assumptions. Occupational/Commercial Post-Applicati on Exposure Based on th e current u se patterns and approved registration s for bromadiolone , there are no anticipat e d occupational or commercia l po s t-applicat i on exposures . All post-application activities (e
. g . , removing dead rodent carcasses) for b romadiolone include the req uirement of waterproof gloves; therefo re , exposures are expected to be n eg ligible. Conclusions Based on the use sites and active registration s for bromadiolone , short-term occ upational handl e r dermal and inhalation exposures are expected. During Registration Review , H E D will reevaluate the points of departure, toxicity endpoi nt s , a nd uncertainty facto r s used for ri s k assessment purpose s . Based upon that infonnation , and u s ing updated policies and body weig ht assumption s, HED will conduct a handl e r exposure assessment for bromadiolone. Occupational postapplication expos ure s are not anticipated for bromadiolone. Add iti onal information r egarding the maximum number of refillable mouse and rat trap/bait stations within the 50 or I 00 foot perimet e r of bu ild ings m ay a llow HED to b et ter estimate potential occupational handler exposure and ri s ks. Public H ea lth and Pesticide E pid e mi o l ogy Data 

### As part of the Rodenticide Risk Mitigation Decision (RMD) , and the subsequent Notice of Int e nt to Cancel (NO I C), the E n v ironm en tal Protection Age nc y's Office of Pe s ti cide Programs' PRD requested an analysis of human incident s involving exposure to rodenticides in 2011 (D 395567 , S. Recore , 10 / 28 / 2011) and updated in 2015 (D430176 , S. R ecore , 1 11 17 / 20 1 5). For this evaluation. the Agency consulted the OPP Incident Data System (IDS) , the Na tional Pesticid e Information Center (NP IC)
. Centers for Di sease Control and Prevention/Nati o nal In stitute for Occupational Safety and H ea lth (CDC/N I OSH), Sen tin el Event Notification System for Occup atio n a l Risk

- Pesticides (SENSO R ) , and Agricu l tural Health Study (AHS) database s for pesticid e incident data on th e active ingredi e nt bromadiolon e .

P age 8 of3 1

### For the Main IDS , which contains in cidents resulting in highe r severity outcomes (i.e., death , major and moderate incidents) from Janu ary 1 , 20 10 to May 27,2015 , from January 1 , 2010 to May 27, 2015, there we re 1 2 incidents reported for the si n gle chemical bromadiolone in the database. Eleven of these incid e nts were classified as mod e rate severity and one of these incidents was cla ss ifi ed as major severity. An in cident descript ion classified as major severity involved several children w h o were hospitali zed after coming into contact with bromadiolone. Bromadiolone was placed atop a high filing cabinet in a classroom , and children accessed the a.i., whic h they mistook for ca nd y. In Aggregate IDS , from Januar y l , 2010 to May 27 , 2015 , there were 171 incident s reported involving bromadiolone. Fifty two in c idents were classified as having no or unknown ef fects , and 119 incident s were classified as minor severity
. A query of SENSOR-Pesticides from 1998- 201 1 id ent ifi ed a total of 15 cases involving bromadiolone. Of these, t en cases involved a s in g le active ingredient bromadiolone. One case was hi gh severity, two cases were moderate seve rit y a nd seve n cases were low seve r ity. Four cases were intention al in gestion for self-harm. These four intentional cases in c lude the high seve rity case and both moderate severity cases as we ll as one low seve ri ty case. The Agency will con tinu e to monitor the incident information and provide an updated re view of incidents , considering pre- and post
- mitigation incid e nts separately, when the information becomes available. 

### To l era n ce Assess m e nt an d I n ter n ationa l Ha rm o ni zat i o n There are no tolerance s for bromadiolone, and thu s no concerns with regard to international harmonization. 

### E n v ir on m e n ta l Ju st i ce Potential areas of environmental justice concern s, to the extent possible , will be considered during Registration R ev iew, in accordance with U
. S
. Exec utive Order 12898 , "Federal Actions to Address Environmental Ju stice in Minority Populations and Low-Incom e Populat ions," ( http :// www . archives.gov/ federal-register / executive-orders/ pdf/12898
. pd Q
. As a part of every pesticide risk assessment , OPP considers a large variety of consumer subg ro up s according to we ll-established procedure s. In line with OPP polic y, l-IED estimates risk s to pesticide exposures that are based on activities in and around th e home that in vo lve pesticide u se in a residential se tting. Whenever appropriate , these non-dietary expos ures are calculated based on home use of pesticide product s and assoc iated risks for adult applicators and for toddlers, youths , and adults e ntering or playing on trea ted areas post-application are evaluated. 

### C umul at ive Unlike other pesticide s for which EPA ha s fo ll owed a cumulative risk approach based on a co mmon mechani s m of toxicity , EPA has not m ade a common mechanism oftoxicity finding as to bromadio1one and any other substances and bromadiolone does not app ear to produce a toxic me t abolite produced by other s ubstances. For inf o rmation regarding E PA" s efforts to determine w hich chemicals hav e a common mechanism of toxicit y and to evaluate th e cumulative effects of
Pa ge 9 of3 1

### suc h c hem ica l s, see the policy statements re leased by E PA's Office of Pesticide Programs concerning common mechanism determinations and procedur es for cumulating effects from substances found to hav e a common mechanism on EPA 's website at http :/h .nvw . epa . gov/ pes ticidcs/ cumulative /. Human Studie s T he risk assessments HED ant icipates to conduct during Registration Review for bromadiolon e will rely in part on data from studies in which adult human subjects were intentionally exposed to a pest ic ide to determine their dermal and inhalation exposure. Many of these stud ies, involving exposure to many different pest icides, comprise generic pesticide expos ure databa ses suc h as th e Pesticide H and lers Exposure Database ( PHED) , th e Agricultural Hand le r Exposure Task Force (AHETF ) database, an d the Outdoor Res id e nti a l Ex posure Task Force (O RETF )
. EPA ha s reviewed all the s tudie s s upporting these mu l ti

- pesticide gener i c exposu re database s, and has found no clear and conv incing evidence that the conduct of any of them was either fundame n tally unethical or s ignificantl y deficient relative to the ethical standards prevailing at the time the research was conducted
. All applicable requirem ents of EPA's Rule for the Protection of Human Subjec t s of Research , Tit le 40 of the Code of Federal Reg u lations (CFR) Part 26 , have been satisfied, and there is no regulatory barr ier to continued r e li ance on these studies. Dat a D e ficiencies The following toxicology data are needed to suppo rt the reg i s tered uses of bromadioJone:

• A s ubchronic derm a l toxicity s tud y (§870.3200) • A subc hronic i nhalation toxicity study (§870.3465)

Page 10 

### of3 1

### References Habiba, J. Rodenticides : Summary of Hazard and Science Policy Council (HASPOC) Meeting on October 1, 2015: Recommendations on Data Requirements for Rodenticides. TXR # 0057326
. 12115 / 2015. Kasting , G. B. and M.A. Miller (2006). "Kinetics offinite dose absorption through sk i n 2. Volati le compounds." Journal of Pharmaceutical Sc iences 95(2) : 268-280. Kasting , G. B. , M.A. Miller , et al. (2008). "A Spreadsheet-Based Method for Estimating the Skin Disposition ofVolatile Compounds: Application to N , N

- Diethyl-m-Toluam i de (DEET)." Journal of Occupational and E nvironmental Hygiene 5(1 0): 633-644. Wang , T.-F. , G
. B. Kasting , et al. (2007). "A multi

- phase microscopic mode l for stratum corneum permeability. II
. Estimation of physicochemical parameters and application to a large permeabi l ity database." Journal of Pharmaceutical Sciences 96(11 ): 3024-3051. Miller, M.A. and G. B. Kasting (201 0). "Toward a Better Understanding of Pesticide Dermal Absorption: Diffusion Model Analys i s ofParathion Absorption in Vitro and in Vivo." Journa l of Toxicology and Environmental Healt h 73(4): 284- 300. Recore , S. Rodent i cide: Tier I (Seeping) Review of Human Incidents and Epidemio l ogy Assessment. D426573. 11 / 24/ 2015. Recore , S. Rodenticides Tier II : Review of Human I ncidents. D395567. 10/ 28 / 20 1 1. Redden , 

### J. The HED Chapter of the Reregistration Eligibility Decision (R Document ED) for Bromadio l one. Case No. 2760; Chemical No. I 12001. 09 /27 / 1995 Redden , 

### J. RED Chapter Addendum to the HED Chapter of the Rereg i stration E ligibility Decision Document (RED) for Bromadiolone. Case No. 2760; Chemical No. 1 12001. 04/ 04 / 1996


### Atta chm e n ts 1. Use Profile 2. Chemical Identity Table 3. Physicochemical Prope11ies ofTechnical Grade Bromadio lone Table 4. Endpoint Selection Table 5. Toxicity Profile Tables 6. Toxicology Data Requirements Table

Page 11 

### of 3 1

### A ttac hm e nt 1 T a b le A
. I. U se P r o fil e f o r Br o mad io lo n c. Occ up ati o na l. M ax . E

P

A Prod uc t % Active Applic ati on Ex pos ur e Appli ca ti o n Re g . Na m e Fo rmu la tio n 2 I ngre d ie nt Us e S it es T a r get P es t s PPE / C i o thin g 3 m ethod s4 E x pec t e d ? R a te/ loca ti o n. - No
. 1 Y IN Rats ( R

a t i

o na le) Bro madiolo n e 27 0

- 3 71 2 .5% NA 2.500 % NA NA N A NA N (Not lind-use) NA Conce nt m te In a n d a

r o un d Agri cultu m l llro mud io lo n e RT U p la ce Buildin gs; Ind ustr ial No rw ay rats Rats - 1.5 oz . and co mrn c r c in

l { in c l. warfarin

270-372 Bait Pe ll e t s/ J us t pac k s 0
. 005% b u i ldi n gs: i ns id e re s ist a nt), roo f LSS
. LP
. SS. W G pl a ce pa c k s . 3

- 10 N ( R TU P l a

ce 0
. 00 00 5 O n

e llitc I I co n tain in g s hi ps . t ra ins , aircraft r a t

s. h o use pac k s . Mice- I pn c k s ) Pl ace P ac k s p ell e t s ( 1
. 5 oz . ) and r c lm c d m ice pac k ponlt e nnin n l bu i ld in gs B u rrow s. n m way s. har d -t o -reac h areas: Orornadio lone In a n d aro u nd Ag r i. N o r

way rats Bai t Bar : Jus t Wrap ped ba i t Build i n gs a n d (i n cl. warf arin- R ats- 2 oz . bars. 270- 3 73 o n e B ite II bar : bar / chun k s (2 0
.005 % lndu s tria l / co mm crc i: tl res ist a nt) , r oo f LSS , LP
. SS. WG 2

- 8 ( burro ws N (W r ap pe d 0
.00005 Ju s t o n e Bite II oz . ) buildin gs in cl ud in g r a t s . h o u

se l owe r rate)
. Mi ce - bait) Bai t Chunk s tran s po rt ve h ic l es mic e I bar (sh ip s, t rain s . aircra11)
. p o n o r t ermin a l bui l di n gs Maki 7 1

73- 1 7 3 R o denti c id e NA 1
. 000 % NA NA NA NA N ( n o t E nd

- u sc) NA 1.0% Dry Co n ce nt ra t e 7 1

73

- 1 7 4 M aki Tec hnical NA 98
. 5 00% N A N A N A NA N (No t End -u sc ) N A In doo r /O u tdoor : Home s. f ood Norway r a t

s proce ss in g faci li tic s . Maki P a raffin Pe ll et s co mm e r c ial b ui l

di n

gs . ( in cl
. warf ari n- Rats
- 4 -1 6 oz . 7 1 73 -1 87 P arani n ized 0
.005 % r es ist an t ) , ro o f LSS
. LP
. SS
. WG Y ( loo se pe ll e t s) 0
. 00005 P e lle t s ( bu l k ) Ag
. bui ldin gs, r a t

s. h o us e Mi ce - 1 /4

-

2 oz . tran spo rt ve h icle s . m ice d oc k s/

po n/ tcmt i n u l buildin gs: t ra s h cn ns Ma ki Rat a n d R TU B ai t p la ce N o burrow s : ll o m cs. N o rwa y rats Rat s - 15 o z . f ood p rocess in g p ac k s. 3

- 10 N ( R TU P la ce 7 1

73- 1 88 Mo use B a it pac k s ( paraffi n 0
.005% f ac ilit ie s . ( in cl. warfarin- LSS , L P
. S S. W G p acks
. Mi ce - 1-3 pac k s o r pe ll ets) 0
. 00047 Pac k s (Pe llets ) pe ll e t s ) ( 1 5 oz . ) indu s t ria l /c o mme r c ia l re s istant)
. r oof p ac k s

- ----·--- 

### Pa g e 1 2 

### of 3 l

### T ab l e A. I. 

### Use P ro fil e f o r Br o m a dio lo ne. Occupa tion al. Max. ' 

### E PA Product % Ac tive App lication Expo s u re Ap p licati on R

eg . Name Formulation2 

### I n

g red ient Use Sites Target P es ts PPE/C iothing 3 

### method s 4 

### Ex pe cted ? Rate / loca ti on.- No. 1 YIN 

### Rats ( Ratio na l e) bu i ldin gs, tras h ca ns. ra t s, h ouse ag, tran spo n ve hi cles. mice d ocks. po n s. termin als. e t c. N

o bur ro ws; h o m es. f ood process in g No r way ra t s Rats - 2 oz . fa ci liti cs, ( in c l. warfari n - p ieces. 2

- 8 p ieces 7 1

73

- 189 Maki Para mn Ha u bars( llb , 0.005% i n d u

s tria l / co mmer cia l resis ta nt ). roof LSS, LP

_ . SS. WG (Sewer

- I e nt ire N ( B ait bl ock s) 0.00005 I B l

ock s 2 0'-) build i n gs, tras h ca ns. r at

s. h o use b l ock o n w i r e o n a g , mm spo n vehicle s. mi ce manh o le ). Mi cedo ck s, po ns , I piece t en ninal s . e t c . No burro ws: h o m es. Rats

- 28 g b l oc k s. f ood p rocess in g 3

- 16 bl oc ks f aci litie s. No rw ay ra ts (Se w e r- I b l oc k Maki Mini B ait B l ock s indu s lri al /co mme r c i a

l (i n c l. warfari n- o n wir e o n 7 1

73

-202 Bl ock s (2 8 g) 0
.005% b uil din gs, trashcan s, r es i stant). ro o f I. SS, LP , S S, W G manhole ab o ve N ( Bait bl oc k s) 0.00005 n u s, h ouse hig h water line o r n g, tran spon vehicle s, mi c e on b oard : 16 d oc k s, po n s, b l o ck s/ manh o le )
. t e nninal s. e t c. Mi ce- 1

-2 bl ocks No b urro \\ s: h o m es. f ood process in g No r way ra ts Maki fa c i l i

ti cs, Cann o t calcuhu e: R

o dcruicidc RT U 13uit Puck s indu strial /co mmercial ( in c l. warfarin

- Rats- 4- 16 pack s. N ( RT U Pla ce neg l ig ibl e 7 1 73

-2 08 0. 005 % re s is tant), r oo f LS S
. LP , S S , W G Bail Pa ck s ( pe ll e t s) ( NS } buildin gs, l rashcan s. ra ts. h o use M icc- 1-4 pac k s pa ck s) exp os ure ( P

e ll e t s) a g. trnn spo n vehicle s. mi ce exp ec t e d d oc k s. po n s. t e nn inal s. e tc . ll o rn cs, f oo d process i n g faci liti es, Norway nn s Maki Paramn Pellets indu striallcommcrci a l ( in cl. warfarin- Rats· 4- 1 6 oz . Y ( l oose parnllin 7 1 73

- 2 12 R o d enticide 0
. 005% buildin gs, trashcan s. r cs is talll )
. r oo f LSS. LP , S S
. W G pe ll ets . Mi ce- 0.00005 Pe llets: ( bulk } a g. tran spo n vehicl es, ra ts. h o u se lf .t- 2 o z . pe llet s) d ock s. pons. m ice lcnninal s. e t e. No burr o ws: home s. Norway rats Ra t s - 28 g b l ock s. Maki f oo d pr o ce ss in g ( in c l. warfarin- 3- 16 bl oc k s 7 1 73

- 2 15 R o denticide Mini Olocks (28 0
. 005 % facilitie s, re s is tant). ro o f I
. SS , LP , SS , W G ( Sewe r- I b l o ck N (parallin 0.00005 Mini Bl oc ks g) indu s trial /c ommerc ial**raL ~.**  h o use o n wire o n bl o ck s) build i n gs. tras hcan s, mi ce manh o le a g. tr a n spo n v ehicl es.**hin ~t.**  o r 

### Page 1 3 of 31

### T a bl e A. I. 

### Use Pro fil e for B ro m a di o l on e. Occupational. Max. EPA Product % Active Applicat ion Expo s ure Applicat ion R

eg. Name Fo rm u lation2 

### Ingredient Use Sites Target Pests PPE/C iothing 3 methods 4 

### Expected? Rate/ locat ion.- No. 1 YIN 

### Rats (Rational e ) d oc k s. po n s. above high wmer tem1inal s. e l c . line or o n beard , 1 6 bl oc k s/

manho le
. )
. Mice · 1 · 2 bl ocks No burro ws: h o me s. Rats- 0.42 oz . food processi n g No rway mts packs , 7

- 36 Y (p la ce pack s. facilitie s, Bromndiolo n e RT U Paste Oait i nd u s tria 1/commerc ia I (i ncl. warfarin- packs/ pouche s . bu1 pas te ma y be 7 1

73

-297 Pas te 0901 Pack s (0.42 0.005% buildings. lr as h co ns, re s is tant ), r oof I. SS
. LP , SS. WG Mice- 1-4 0.42 removed and 0
. 00005 07. ./ 12 g) ag , tran s pon vehic le s. rats, h o use 07.
. p laced in bait docks, pon s. mice pack s/ pouches , 8- s lUt ion) tenninal s, e tc . 12' , 15 day s: h om es and o th er pcnnan cnt o r tem porruy re s idence s. food proce ssi n g facilitie s. industrial Wld commercial buildin gs. No rwa y mts Paraffin B l oc k trash re ce ptacle s. ( incl. warfarin12455-34 Co ntmcAII- ( lib s lab with 4 0
.005% agriculn
. tral :md re sis tant). roof LSS
. I.P .SS.G Rats - 4 oz. s lab s. N ( paraffin cake) 0.00005 weather Cake oz . piece s) public buildin gs, rats, h o use 1 -4 4 s lab s tran spon mice vehicle s (ship s. train s, aircrnfi) , d oc k s and pon o ftcnninal buildin gs and r e lated s tru c tures around a n d associated wi th the se si t

es burr0 11 s: h o me s :nd o ther pem1ancm o r temp o rary re sidcn ccs. f oo d process in g No rwa y rats Co ntmc Rat and facilitie s. (i n cl. warfarin- Rat- 3

- 16 oz. bait. Y ( Meal bait, 12455-36 Mouse Boil Bulk Bait
. Meal 0.005% indu s trial ru1d rc s is tont) , roof LSS
. LP , SS. WG Mice- 1 /4 t o 2 oz. g rain s) 0
. 00005 commercial buildin gs. rats, hou se bait tras h receptacle s, mice a g ri cultuml ru1d publi c buildings, tran spon 

### Pa ge 1 4 of3 1Ta bl e A.l. Usc P r o fil e f o r B ro m ad io l onc. 

### O cc up a tional. Max. EPA Pro du c t % Ac tive Application Ex po s ure Appli c ation R

eg . Name F onnu lation2 

### Lngredient U s e Site s Tar g et P es t s PP E/C iothing 3 

### methods 4 

### Exp ecte d ? Rate/ location
. - No. 1 YIN 

### Rats (Rationale) ve h icles (s hip s. trains
. aircra ft ), docks and port of t c n11 i n al bu ildi n gs an d rc l med st ru c tur es arou n d and associated with th e se si t

es . burro w s: h o m es n n d o th e r pc n11an c m o r temp orary r es id en ces, f ood process in g facilitie s, indu s trial and co mm e r c ia l buildings. No rw ay nu s tras h r ecept ac l es. ( in c l. wa rf arin

- R ats
- 4

- 16 oz. 12455

- 69 Co rHr ac P arallin P e ll e t 0.00 5 % a g ricullural and r es is ta nt ) , r oof SS.G b ait. Mi ce- 1 /4 t o Y (G r a nul ar 0
. 00005 R

o d

e nt ici d e Bait publi c buildings. r ats, h o us e 2 oz. b a it p e ll e t) tra

n spo rt rni ce ve hi c l es (s hi ps, tra i ns. ai rcra ft ), do c k s ru 1d po rt of t e m1 i n al b u

i l

di n gs a n d re l a ted st

ru ctures around and associat ed "i t h t

he se s i

tes. 12-155

- 70 Tec h nical Orornadi ol onc NA 96
. 500% NA NA NA NA N (Not e n d-u sc) NA h o m es a n d o th e r pe m1 a n e nt or te

mp ora r y r

esi d e n ces. f ood p rocess in g f a ciliti es , indu s trial a nd No rw ay ra t s Rats - 1
. 5 oz. Co nt rnc Rat a nd R TU P la ce co mm e r c ial buildin gs , (i n c l. war f ar i

n · pla ce pa ck s , 2-1 0 N ( R TU place 12

4 55 · 75 0. 0 0 5% tras h re ceptac l es. r es is ta nt ). roo f l. SS. L P
. SS. W G 0 .00005 M

o use 13a it Pa c k s ( I. 5 oz .) a g ricullural and rats, h o use packs. Mi ce- I pa ck s) publi c buildin gs, mi ce pack tran s port vehicle s ( s hip s, train s . airc raft ). do ck s and port o ftcnninal buildin gs and r e lat ed



### Pa ge 1 5 of3 1Tab le A . I. 

### Use P r ofile for Bromadio lone. 

### Occupational. Max. EP A Product %Act ive App l icat ion Expos ure Application Reg. Name Formulation 2 

### I ngredient Use Sites Target Pests PP E / Cioth in g3 

### methods 4 

### Expected? Rate/ location.- No. 1 

### YIN Rats ( Rationale) s tructure s around and nssocia ted with the se si te s. home s and other pcm1anent or temporar y re s idence s. food proces s in g facilities , indu s trial and co mmercia l bui I din gs. tras h Norway rats receptacle s, Rats· 1.5 oz . Contrac RT U Place agric ultural and (i n c l. warfarin- place packs. 2-10 N (RTU Plac e 1 2455

- 76 0
. 005% re s is tant) , roof SS.G 0
.00005 Rodenticide Pa ck s ( 1.5 oz .) public buildin gs, rats. h o use pla ce packs
. Pack) tran spo rt vehic l es mice Mice- I pack (s hip s, train s. aircrafi) , dock s and pon oftenninal buildin gs and related stru cture s aro und and associated with the se sites
. Industrial and commercia l buildi n gs. trnsh rcccptncle s, agricu l tural ;md public buildings, Norway rats , Rats- I o:t . bait 12455-79 Co ntrac A II- Bait Bl ock s ( I 0
.005% tran sport (s hip s. roof rats and SS.G bl ock s. 3-16 N ( Parall]n 0 .0 0005 Weather Blox oz .) train s. aircrafi) , d oc k s h ou se mice bl ock s. Mice- 1-2 bl ock) and pon o f tcnninal blocks buildings and related s tructure s around and associated with the se s ite s . h o me s and o th e r penn anent or temporary re s idence s. Co ntrac Supe r Oait Block s (8 food proce ss in g Norway rat s. Rats - 8 oz. bait N (Parani n 12455-82 0
. 005% facilitie s, LSS. LP. SS, WG b l ocks , 1-2 0.00005 Size Blox oz . ) indu s tri al and roof rats blocks
. b l ock) commercial buildin gs, tras h re ce pt ac le s. agricultural and

--- 

### Page 

### 1 6 of 31

### Tab l e A. J. Use Pr ofile fo r Br o ma d io l o ne . Occupational. 

### Max. EPA Product %Active Application Exposure Appl ication R

eg. Form ulation2 

### U se Sites Targe t Pests PPE /C iothing 3 

### Expected? Rate/ locat ion.- No
. 1 

### Name Ingredient methods4 YIN 

### Rats public building s, 

### (Rationale) transport vehicles (ships, train s. aircraft)
. docks and po rt of t erm in al bui l dings and related s t

ruct ur es around and associated witl1 the se sites. homes and other pennanent or temporary residence s, food proces s ing facilitie s, industrial and comme r cial buildings , Rat- 0.88 oz . Co ntrac trash receptacles , Norway nlts , place pack s, 4 -1 6 1 2455 -86 R o demicidc RT U 13ait Place 0
.005% ag ri cultura l and roof rat s and SS.G place pack s. N (RTU Place 0.0000 4 Pla ce Pacs packs (0
. 88 oz . ) pub I ic buildin gs, hou se mice Mice- I place Pack) transport pack vehicle s (s hip s, train s. aircrall) , docks and port of tenninal buildings and related s tru ctu r es around and associated witl 1 th ese si te s. Industrial- h omes a nd ot h er pemmn e nt or temp orary residence s, food proces s ing facilities , industrial and Norway rats co mm ercia l building s, (incl
. warfarin- Rats- I 07
.. bait 12455-133 Con tra c witl1 Bait Blocks (I 0
. 005% trash r ecep tacles , resistant), roof LSS , LP. SS , WG blocks , 3 -16 N (Paraffin 0.00005 Lurnitrack oz . ) agricultural a nd rat s, house blocks
. Mice- 1-2 Block) pub I ic buildings , mic e blocks tran sport vehicles (s hip s, t rain s, aircraft) , docks and port of tem1inal buildings and related struct ures around and 

### Page 1 7 

### of3 1T ab le A. I. Use Profile for Brom a di o lonc. 

### Occupational. Max
. EPA Product % Active Ap plic ation Expos ure Application Re g. Name Fo rmul at ion 2 

### In gredient U se Sites Ta r get Pe sts PP E /C lothin g 3 

### m ethod s 4 

### Ex p ec t ed? Rate/ l ocation.- No. 1 

### YIN Rat s ( R

atio n a l e) as sociated with the se sites. Ag- a g ricultural building s and manmade agricu It ural s tm ctures constmc t cd in a manner so as 1 0 be vu ln erab l e t

o commensal r ode nt invas io ns ancVor to harboring o r attra c ti n g r

odcm infes tation s. In dus trial- h o m es. o t

her pcm1ancnt o r temp orary re s idence s. food processi n g facilitie s. indu s trial and commercial buildings
. trash Rat

- a -rest receptacle s, Norway rats, Rats· 4-16 oz . Y (Gran ular b ulk 67517- 3 4 Bulk Pe ll e t s 0 .0 05% agricu ltu ralmtd roof rats. h o use I.S S. LP. SS. WG bait. Mice- 1 /4 to 0
.00005 pell e t s pub l ic buildin gs. mi ce 2 oz . pellet) tran s por t vehicle s (s hip s. train s. ai r

craft). docks and po n o f tcm1inal bui l din gs Ag· I00' of ag . Buildin gs Indu s trial- h ome s. o ther pcmmncrc o r temporary re s idence s. food proce ss in g faci l itie s, indu s trial Mou se-a -rest and commercia l Mice- 1 /4 • 2 oz . 675 1 7-35 pe ll e t s 13ulk Pellet s 0
.005% buildin gs, tr as h Ho u s e mic e LSS
. 1.1' , SS, WG bait Y (Loose p e ll e t ) 0.0000 1 re ce pta cles , agricul tural ru1d pub l ic buildin gs. tran sp o n vehicle s (s hip s, train s. aircraft ). 

### Page 

### 18 of 31T ab le A. I. Use Profile f or Bromadiolone
. Occ upati onal. Max
. EPA Produ ct % Active App l ication Ex po s ure Application R

eg. Formulation2 Use Sites Ta r get Pe sts PP E /Ciot hin g 3 Ex pect ed? Rate/ location.- No. 1 Nam e Ingredient m eth ods 4 Y IN Ra ts ( R

at io nale) dock s ru1d p o rt o f tenn in al b u i l

d ings. Indu st rial and co mmercial buildin gs. trash receptacle s. No rway rats. Rats- I. 5 o z . 675 1 7-37 Rat-m ou s e-a- RT U Pla ce 0.005% agricultural and r oo f rats. h ouse LSS. I.P, SS, WG pack s, I0 pack s. N ( RT U Place 0.00005 re st Place Pack Pack s ( 1.5 0 1
. ) pub I ic buildin gs. mi ce Mice

- I place Pack ) tran s po rt , d oc k s. pon pack of t ennina l bui l di n gs, etc . In and arou n d No rway R ats. re s idential bui l din gs, R oo f Rats and Rat s - I oz . bait 72500-19 S ma ck er A a it Wax Oait 0
.005% Indu s trial and I l o use Mice , SS.G bl oc k s, 4- 16 N**(Wa.~** bait 0.00005 B l

ocks (I oz.) agricu ltural buildin gs a nd th e ir bl oc k s. Mice- I bl oc k ) ru1d s imilar man-mad e In fested neas block s tructure s. etc . In and around h ome s and ot her pcnnaru..,ll or temp o rary re si d e n

ces. f oo d processi n g fa c il itic s, indu s trial m1d co mm ercia l b uil di n gs. tras h Rat s I oz . bait r ece pt acle s, No rway rat s . bl oc k s. 6-7 8 2744- 1 Rmimor Wax Wax B l oc k s ( I 0
.005% agricu ltural :md roof rats , h ouse SS, CRG blocks. Mice- 1-2 N (W ax b l oc k ) 0.00002 Bl ock 07 .) publi c bu il dings. mi ce bl oc k s, every 6'

- tran sport vehi c l es 16 ' per l oca tion (s h ip s, train s, aircraft)
. d ock s tuld pon of tenninal building s and related Sl ru ctun. :s around and assoc iated wi th th ese si te s . h o me s and o th er R

TU Wrapped perman en t or No rway rats, Rat s - 0 .38 oz . 82744-2 Ratim o r So ft So ft Bait Bags 0.005% temporary r oof rats , h ouse SS, C R G bait bag s , I0-42 N ( R TU ba it 0.00005 Bait r es iden ces , fo o d bags
. Mice- 1-2 ba g) (0.38 oz .) processi n g fac iliti es , mi ce bags industrial and 

### Pa ge 19 of 31T a ble A.l. 

### U se Profile for B ro madi o looe. 

### Occupational. Max. EPA Product %Act i ve Application Ex po s ure Applicati on Reg. Na m e Forrnulatio n 2 

### In g redie n t Use Sites Tar get P ests P PE /C ioth in g 3 

### m ethod s 4 

### Ex pect ed? Rate/ location.- No. 1 YIN 

### Rats ( Rational e) commercial building s. trash rcccptnclc s, agricu l tura l rutd publi c buildings , tran spo rt vehicles (ships. trains
. aircraft ), dock s and port of tcnninal buildings a nd**rc at~ll**  str u ct ures arou n d and associmcd with th ese sites
. Bri grutd SB Soft Wrapped Wax Indu s trial and No rway rats , Rats: 0.35 oz. bait N ( RT U bait 87235-1 Bait Son Bait Bags 0.005% agricullurnl use s ite s, r oo f rats. hou se LSS. LP. SS. WG bag s. I 0-42 bag s. 0.00005 R

ode nti c ide (0 .35 oz . ) as o thers mice M i cc- 1-2 bags . bag) Brigru1d Wl3 Indu s trial rutd Norway rats, Rats: 4- 16 blo c k s. 87235-2 Wa.x Block Wa.x Blocks ( I 0
. 005% agricullural usc si tes , r oo f rats. hou se I.SS
. LP. SS. WG 1 5'-30'. I0 days : N ( 13ait block ) 0 .00005 oz .) Mice : 1-2 block
. R

o denticide as ot h ers mice 8'-12', IS day s Bromadi olonc 270-371 2.5% NA 2
. 500% NA NA NA NA N (No t EUP) NA Co n ce ntrate I n a

nd nrowtd Agricullural Bro madi ol onc RT U Place Buildin gs: Industrial No rwa y rats Rats

- 1.5 oz . Bait Pell e t s/

Just pack s and commercia l ( in cl. warfarin- place pack s. 3- 1 0 N ( RT U Place 270

- 372 One Bite II con tainin g 0 .0 05% buildin gs: in s ide re s i stant). roof LSS. LP
. SS
. WG packs
. Mice- I pack s) 0
. 00005 s hip s, train s, aircraft rnts , house P l ace Packs pellets ( 1 .5 oz .) a nd related mi ce pack port/ t cnninal building s 13urr O

\\ S, runway s, Bro madiolonc hard-t o -reach areas : No rway rats In and around Agri
. Rats· 2 oz . burs, Ba it Ba r : Ju s t Wrapped bait 13ui l dings a11d (i n cl. warfarin- 2 -8 (b urr ows N (Wra pp ed 270-373 o n e ll itc II bar: bar /c hunk s (2 0.005% r es is tant) , r oof LSS , L P, SS , WG 0.00005 Ju st o n e Bite II oz .) In du s tri al/co mmercia l rats, h o use l ower rate)
. Mice- bait) Bai t C hunks buildings incl u ding mice I bar tran spo rt \'Chicles (shios. train s.


### Page 20 

### of 31

### Ta bl e A. I. 

### Use Pro fil e fo r B ro m a

di o l o n e. EPA P roduct %Ac tive Application R

eg. Fo rrnu la t ion 2 Use Si tes Tar get Pe s t s P PE /C ioth ing3 No
. 1 Na m e I n g r e di ent me th ods 4 aircraft). port or tcm1inal building s Maid 7 1 73- 1 73 R odenticide NA 1. 000% NA N A N A N A I 0% Dry Con centrate

- 1 All end-u s c products include the following re s trictions: Do not apply directl y to food or feed crops. Do not broadcas t bromadiolonc. 2 RTU = ready-to-usc fonnulation Occupa t io nal. M ax. Exposu r e Application Expected? Rate/ locat ion.- 

### YIN Rat s (Rationale)

N (n ot EU P ) N A

---·-··-···------ -·-- -

3 PPE = Pers ona l protective equipment. LSS 

### = long sleeved s hirt
. S = s hi rt. LP 

### = lon g pants, SS =shoes & soc ks. WG = waterproof gloves. C RG = chemical-resistant gloves. G = g l

oves. All labe l s include a minimum of s hoe s a nd socks plus g love s. and walerproof g love s whe n d is po s in g of used bait o r roden t carcasses.**~U nl** **ess** oth erwise sta t ed, treatme nt location s for rat s a r e to be p l aced eve r y 1 5"-30' and trea tm e nt l oca ti ons for mi ce a r c to be p l aced eve r y 8'-12 '. T r ea tm ents a r e to be con tinu ed for I 0 or 1 5 days (o r unt il rodent act iv ity ceases) for rats a nd mic e. respec ti ve ly.



### Page 2 1 

### of 3 1

### Attachment 2 TABL E A.2 . Bromadiolon e Nom encl a ture . Chemical structure 

# W' OH C

H C

H2 CH-o-o-Br OH6
- -
Common name Bromadiolone I U PAC name 3-[3-(4'-bromobiphcnyl
- 4-y l )
- 3 -h yd r oxy-1-ph e n y lpr opyl) -4-h ydroxyco umarin CAS name 3 -[ 3(( 4' - bromo -[ 1

. 1 '-b iphn yl )- 4 - y l )-3
- hydroxy- 1 -phenylpropy l ]
- 4 - hydroxy-2H-Ibenzopyran - 2 one (9CI) 3 -[-[ p-( p-bromophenyl)-hydroxyphenethyl } benzy l- 4 - hydroxycoumarin](8C I CAS r egist ry number 28772 - 56-7



### Page 22 of3 1

### Attachment 3a Tab l e A.3.a. Physicoc h emica l Properties of Bromadiolone. Parameter Value Reference Melling poin t 205

- 2 1 0 ( 0 C) Ph ys ical State Wh it e Powder Density 0.33g/cc

olvcnt so lubility (giL at 25 ° C) Water: 6.1 ppm: hexane: < 0.0 1 g/ I OOml: ethanol: MR ! D s 0 .5 g/ IOOml: dietl1)l ether: 0.0 14 g/ I OOml: acetone: 1.15 g/ IO Oml 41 7 1 700 1.41717002. 41 7 17003,46359001. Vapor pressure 2 x 1 0-6 Pa (at 20 ° C) 42 66780 1 Dissociation constant. pK. 5. 73 in water Octanol/wa ter partition coenicicn t 4.3 Log( Pow) S tability 97.55% to ! 03.3%



### Pa ge 23 of 31

### A tta c hm e nt 3 b D e rm a l Penetr a ti o n C alcul a t i on s ( http : // www . c d c . gov/ ni osh/top i cs/ s ki n/ finit eS kinP e rm Ca lc
. html ) 

## Skin Description/ Environment
S p e ci e s : HUMAN H y drati o n : Par tia ll y H ydrat ed Se ttin g : 

### i n v i vo T e mp e r a ture : 32
. 0 ° C Wind ve l oci ty : 0
. 165 m / s 

## Skin Properties
Stratum Co rn e um Thickne ss ( h xx ) '**~tm ]**  

### 13.365 oH 5.00 Diffu s ivi ty (O x x) ' 

## I [ c m 2

### /s ] 1
. 0 5£- 1 2 W a t e r P a rtiti o n 1 80
. 77 C o e ffici e nt (K xx!W )I 

### C leara nc e (k, xxJ w) 1 

### [ s - • ] U nbound F r a cti o n (f u) 

### N on - ionic F r ac tion (f n

o

n) F r a ctional D e p o s iti o n 0
. 0 25 D e p t h ( f d

e p) Tim e Co n s t a nt**(h ~/** **c)** 

### [hours ] 4 72.70 Sa tu ra tion Co n ce nt ra ti o n [ g/c m 3 ] 

### 3.75 1E- 04 ( C s a t) 2 

### S a tura tion do se**(M ~,.** **3** I 

### ru g/ c m 2 

## l 0.01 3 

### V i a bl e E

pid er

mi s 10 0. 00 7.40 6.69£ -08 2 0.47 0
. 0 2
. 3 7 E-0 2 1.00

1 

### XX- > 

### SC (S tr a twn Co rn e um ), VE (Viab le Ep id e rmis), DE (De rm is).

1 

### The conce ntr a t ion of th e per m eant in th e s tr a tu m co rn e um a t sa t ura tion.

• 1 

### The a m ount ofpe rmeant in the deposition zone when it is saturated with the per meant. 

## Permeant Properties
P age 

### 24 o f 3 1 

### D e rm is 2 0 00.00 7.40 6.69 E

- 08 20
. 47 7
. 53E

- 06 2.37 E -0 2 1.00f ••••••••••••••••••••••••••••••••••• • 

### C hemical N am e C h emica l formula CAS# l ogKo w Mo lecul ar weight Me ltin g point Boiling poin t [g/mol] 

### [O

C] [O

C] bromadialone C30H23Br04 28772-56 -7 4.30 703.120

205
. 00 723.00 

### Vapo ur pre ss ur e 

## I [Pa] 2.000E-06 (1.500 1 2334764226E-8 at 

### Initial Amount Number of doubl e bonds N umber of tripl e bonds N umber of ring sys tems Pharmacophore G rain cl ass E ffective Den s i ty ( p e rr) 8.72E-02 2 

### 0 5 

### Abse nt Other 1.935 

### Evaporative properties Eva poration Rate Co nstant {ke vn p) 

### Eva poration/ A b so rption**R~ nr** **P ~tio**  fX cA 

## Vehicle Properties [ern/h)

Immobil e Ve h icle No t Present j ••• •• ••••••••••••••• • • • ••• ••• ••• • ••• • •••• , 

# · · ·

·**v~ i~;"~** **· v~** **i;; i~.iV~·;** **-p;~~~;,~·** 

# · · · 1·



### 1 

## Dosage Scenarios

Permeant 

### fu g/cm2 

### l 0.0872 Immob il e Vehicl e 

### fmg/cm 2 

### l 0.0 4.994E-11
0.091

Removal Timeline Scenario



## fhoursl 0.0 0 Page 25 of 31 

### [torr]) 32 °C

### Total Applied 8.72£

- 02 )lg/ cm 2 

## Description ofDosa2e Scenarios

1 

### 1 At ti me ze ro 

### 0.0872 )lg/Cm 2 

### of permeant was app l ied to the skin
. 

## Maximum Fluxes and Concentrations
Maximum Absorptive F lux (max(J ab s )) Time to Max Abs F l ux Maximum Evaporative Flux Time to Max Trap F lu x Max Mid-Epidermal C oncentra tion (C max) 2.693£ -11 

## I 8.000

1 

### 9.662£-05

2.778£-10 2. 11 2£

- 07 )lg cm- 2 

### h- 1 

### hour s )lg cm- 2 

### h

- 1 

### hours )l g/ cm 3


### Max Mid-Epidermal Free Co nc e ntration (Crrcc ) 4.210£-09 )lg/ cm 3 

### Time to Max Mid-Epidermal C oncentration**tTmn~)** 

## Diffusive Resistance 8.000 h our s



### Skin Layer Diffusive Resistance [em/b) Control 

### Stratum Corn e um 1956.541 98.93 % 

### Viable Epidermi s 2.028 0.10 % 

### Dermis 19.113 0.97%



# ..... .. ... . ... .... .... .....

Total 1977.682 100.00% 

### Effective k p {ctn/11/ 5 .0

56£ - 0 -1 

## General Simulation Parameters

Time Above Se t Co ncentration 1 

### 8.oo h ou r s 

### Ma x S imul a ti o n Duration 8.00 ho u rs 

### S imu l ation Time 8.00 hours

Page 26 of 31 

### 3.004£

- 07 !lM
5.987£-09 !lM

# Results

Calculated Permeant Distribution
Removed E vapo r at e d 

## l

..

## ~?.~~~**~** 

# ......... ..... ..... .. . .. Stratu m Corneum



# ...... . ... . ...... . ... .. .... .. .. .. .... 1 

### V i ab l e Ep i dermis Dermis

Total

T im eS tamp : Time: 20 16/02 / 23 1 5:39:39 Actual imulation Time : 7.136E

-03 seconds 

### 0.0 % 0.0**g/ 2**  

### 0 . 89 % 7
. 7 3 0 £

- 04**g/ cm** **2** 

### 20 .92 % 7 8.96 % 0
. 0 1 8**~g /c** **2** 

### 0.069 fl g/ c m 2 

### 2.49 E -06 % 2
. 173 £ -09**2** 

### 2.57E -0 6% 2
. 244£-09 fl g/ c m 2



### 1 00.76 % 0
. 087**g/ cm** **2**

Tahle. Plot. and Ou t pu t Preparation Time: 0.0 1 3 seconds Tota l Simula tion Time : 0.020 s econd s

ys t em Memory Used :3 4M B JVM vers i o n : 1. 8.0

_ 5 1 Program Ve r s i o n : f

_ 4 c31java

_ v i. O Method Vers i o n : 4C3 L ve r s i

o n 2.4._09
. 0 9 .20 1 0 rev 3 .0



### P age 27 of 31

### Attachment 4
Tab le A
. 4
. 1. Summary o f Toxicological D oses a nd E ndpoints for Bromodi o lon e f o r Use in O c cupationa l Human Health Ri s k A ss e ss me n t" Uncertainty/ R ID , P AD, Leve l of Exposure / Point of FQPA Concern for Study and Toxicological Effects Scenario Departure Safety Ri sk Factors Assessment Dennal Prenatal Developmental Toxicity Study in Rabbit Short-Tenn (1-30 days) UF A= IOX Residential LOAEL = 8 ).lg/k g/day, based on vaginal bleedin g in NOAEL = dams. and 4).1glkglday UFH = lOX LOC for I ntermediate MOE = 100 Term (I

- 6 A dermal absorption factor of I0 % is ass umed for months ri s k assess ment purpo ses I nhalation Prenatal Developm e nta l Toxicity Study in Rabbit Short -Tenn (1

- 30 days) UFA= lOX Re s idential LOAEL = 8 ).lg/k g/day, base d on vaginal bleeding in NOAEL = UFH = lOX dams. and 4).1g/k g/day UF os=fX LOC for Inte rmediate MO E = 100 Tenn(I-6 Toxicity via the dennal ro ut e assumed equivalent to month s oral in the absence of inh a lation toxicity data. Cancer (oral, denna l , Classification: None. Carcinogenicity s tudies not requ ir ed for non-food use . inha lation) a Pomt of Departure ( POD ) = A data pomt or an estima ted po mt that IS dcnvcd from observed do se- respo nse data and u sed to mark the beginnin g of extrapolation t o determine ri sk associated with l o wer environmentally re l eva nt human exposures. O AEL = no o b served adve r se eRect l evel. LOAEL = l owest observed adve r se effect l evel. U F = uncertainty factor
. UFA = extrapolation from anim al to human (intersp eci es). U F H = potential va riation in se n s iti vi ty among members of the hum an population ( intraspccics U Fon = database uncertainty factor: u sc of a s hort-term s tudy for intcm1cdiatc-tcrm risk assessment.. LO C = l eve l or con ce rn .



### Pag e 28 of 31

### A ttachment 5 Acute Toxicity

Ta bl e A.S.l. Acute Toxic ity Profil e for Bromadiolone Guide line St ud y Results Catego r y 870.1100 Oral Acute LD so Rat Between 0.56 and 0.84 mg!kg I 870.1200 Dermal Acute LD so Rabbit 1.7lmglkg I 870.1300 I nhalation Acute LD so Rat 0.43 mg!kg I 870.2400 Acute Eye Irritation Rabbit Irritation. cleared by 4 days Ill 870.2500 Acute D ermal Irritation Rabbit Minimall y irritating IV 870.2600 D ermal Sensitization No data available


### Non-Acute Toxicity

Table A.S. 2. Repeated Do se T ox icity Profile of Bromadio lo n e Gu id e lin e Study, S p ecies MRID (Year) , Dos e Results Levels, C la ss ifi catio n 870.3050 20-day ora l gavage, rat 00 I 07035 ( 1992) NOAEL < 6.4**~glkg** bw / day, not estab l ished 0 , 6.4 , 12.4 , 24.8 LOAEL = 6.4**~tg/k g/** **day** based on**~g/kg** bw/day hemorrhage in orbi tal sin us, nasal cavity and nail bed; anorexia and polydyps i a; internal Core Supplementary bleeding and h emorrhag ic spots on li ver, G l (non-guideline) a nd kidney s . 870.3150 90

- day oral capsu l e, dog 92 1 960 13 ( 199 2) NOAEL = I0**~glkg** bw/day 0,5 , 10 , 1 5,25.50. 100 LOAEL = 15**~g!k gl** **day** based on increa sed J.lg/kg bw/ day prothrombin time and hematuria. Core S uppl ementary At higher do ses. internal hemorrhage, (non

-guideline) co nges ti on and/or edema of spleen, kidneys , lungs, urinary bladder , s mall intes ti ne , liver, thyroid, skin were obse rved 870.3700a Developm ent a l Toxicity, 92 19 60 1 4 ( 1 992) Maternal rat 0, 17 .5, 35, 70 1-lg / k

g/day NOAEL = 35 J.l g/kg bw/ day LOAEL = 70 11glkg /day based on vaginal Acceptable/ Guide I inc bleeding, hypotonicity, pale eyes Developmental

OAEL = 70 11glkg bw/day LOAEL = not established 870.3700b Developm ental Toxicity , 92196015 ( 1992) Maternal rabbit 0 , 2, 4 , 8 !lglk g! day NOAEL = 4**~g!kg** bw / day LOAEL = 8 J.l g/kg/day based on vaginal Acceptable /Guide lin e bleeding Developmental NOAEL = 8 11 glkg bw/ day LOAEL = not established



### Page 29 of 31Ta bl e A.S.2. R e p eated D o s e T ox ic ity Pr ofil e of B r oma di o lo n e G ui de l in e St ud y , Speci es MRID (Year) , Do s e Res u lts L ev e ls, C l a ss ifi cat io n 870.5 1 00 In vitro B ac t e ri a l Gene 42632 10 I ( 1 992) Negati ve. Mut at ion 0 , 3.33- 10 00 J.l g/ pl a t e, There w as no evi d en ce of indu ce d mut ant with ou t S9- m ix colo ni es ove r backgrou nd
. Acceptable/Guide li ne 870.5375 I n vitro Mammalian 42943503 ( 1992) Negative. Cytogenetics 0, 4.49 , 9.99, 25.0. 50.0, There w a s no evidence of chromosome Chromosome Aberration 74.9, 99.9 jl g/ mL aberra t ions induced ove r background, even Assay without S9; in the presence of cytotoxicity at 74.9 u g/ ml 0, 37.5, 50.0, 74.9. 99.9 o r above. J.!g/mL in th e pre se nce of S 9 ac ti vat ion Accep tab le/Guide l ine 870.5395 I n vivo Mammalian 42943504 ( 1 992) Negat ive. Cytogenet ics- No evidence of toxicity in harves ted bone Erythrocyte 400 jlg/kg marrow cells, even though death occ u rred in M icro n ucleus a ss ay in some treated male s and females. the mouse Accep tab le /.e,u ideline 870.74 8 5 Abso rpti o n D is tri buti on 4259680 I ( 1 992) Live r co n ce ntr at io ns we r e meas ured on day Meta bo li s m Exc r e ti o n on e and d ay 200 pos t dos in g. 0.2 11 glkg bw as a s in g le dose. T 1 12 in I iver = 17 day s in phase I of a biexpo nential pa tt ern , and 3 1 8 days fo r phase Acceptable/Guideline 2 , indicating a s ub s tantial rete ntion of bromadiolone in the liver for a long time.



### P age 3 0 of 3 1

### A tta c hm e n t 6 The requirements (40 CF R 

### § 158.340) for the non-food use s for bromadiolone are in Tab l e A.6. Use of the new gu idelin e numbers does not impl y that th e new ( 

### 1998) g uideline protocols were u se d.
Tab l e A.6. Tox i co l ogy D a t a R e q u ire m e n ts G u ide li ne St ud y Ty pe R e quire d S ubmitted S ati s fi e d 870.1 1 00 Ac ut e O ral Toxicity y y y 870.1200 Ac ute Dermal Toxicity y y y 870.1300 Acu te Inh a la ti on Tox icit y y y y 870.2400 A c ute Eye Irrita tion y y y 870.2500 Acute De rm a l Irr itation y y y 870.2600 S kin Se n s iti za ti on y N N 870.3 1 00 90-Day O ral Toxicit y in R ode nts y y y 870.3150 90-Day Oral Toxicity in Non-Rodents y y y 870.3200 2 1 / 28-Day D e m1al Tox icit y y N N 870.3250 90-Day Derm a l Tox i city N N 

### -- 870.3465 90

- Day I nhal a ti o n Toxicity y N N 870.3700 Prenata l Deve l opmental Toxicity Study ( R a t) y y y Prenatal Deve l op mental Toxicity Study ( Rabbit ) y y y 870.3800 Reproduct ion and Fenility Effects y N Wai ved 3 870.4100 Ch ron i c Toxicity ( R odent} N N 

### -- 870 .4 200 Ca rcin ogenic it y (Rat) N N 

### --**Carcino~cnicity** (Mouse) N N 

### -- 870.5 1 00 Bacterial R everse Mutation Test y y y 870.5300 in vitro Mammalian Cell Gene Mutation Tcst l y y y 870.5375 in 1·itro Mammalian Chromosome Abe rration Test 870.5385 Mamma l ian Bone Marrow C hrom oso mal Abe rra tion Tcst 2 y y y 870.5395 M a mm a li a n Ervthrocvte Micronucleus Test 870.6 1 00 Delayed Ncurotoxicitv of Organophosphorus Substances (Acute. li en) C R N 

## - - De layed Neurotoxici ty o f Organophosphorus Substances (28 -D ay . li en} N N 

## - - 870.6200 Ne uro tox i c ity Sc ree nin g Bane ry (Ac ute. Rat) y N Wai ved 3 Ne uro tox icit y Sc ree ningBattery (90

- Day. Rat ) y N Wai v ed 3 870.6300 Developmental Neuro toxicity Stud y C R N 

## -- 870.7200 Co mpanion Animal Safety N N 

### -- 870.7485 Mctabol is m and Ph armacoki netic s y y y 870.7600 Dermal P enet rati on N N 

### -- 870.7800 lrnmun o toxicity y N Waived 3



### .. C R = Co ndr11 o nall y**eq t~~r** **ed** 2 E ith er g uid e lin e s tud y type m ay be u se d t o sat isfy the data requirement (e.g
.. 870.5300 o r 870.5375) 3 S tud y not expec ted to prov id e a lowe r point of depanure (POD) for ri sk assessme nt



### P age 3 1 of 31