### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PRE V ENTION



### MEMORANDUM

DATE: December 1 5, 20 1 5



### SUB J ECT : D iph ac inon e an d Diph a cinone Sod ium Salt. Human H eal th Assessment Scoping Document in Support of Registration R eview

.

PC Code: 06770 I
, 067705 D ec i s i on No.: 502489 Petition No.: NA DP Ba r code: 042629 2 R eg i s tr at i o n No.: NA R egu l a t ory Action: R eg istration Review Scoping Case No.: NA Ri s k A ssess m en t T y pe: Single Chemical/Aggregate TXR No.: NA CAS No.: 82-66-6 MRID No.: A 40 CFR: NA



### FROM : Bridgen Bobowiec

, Biologist**~** 

### Christopher Sc hl osser, Toxicologist

## '-#./5-**~c> -:**  Sumitra Bose Biswas, Chemist Risk Assessment Branch Vl (RA B 6) Health Effects Division (7509P)



# ,, THROUGH: Austin Wray
, Ph.D.

, Toxicologist 

# /4.**~** 

# W**~** Risk Assessment Branch 

### IV (RAB 

### f V) Health Effects Division ( H ED
,**75,Q?~** 

### _**~ ~**  

### Margarita Co llant es , Bio l ogist,

### ~K 1

### ~ Risk Assessment Branch (RAB) II /

Health Effec t s Di vis ion (7509 P )

# ~~~a Davis

, Br anch Chief

# J~~ Risk Assessment Branch 

### VI (RAB6) H ea l th Effects Di vision (7509 P )



### TO : C hri stina Motilall

, Chemical Review Manager Risk Management and I mplementation Branch I ( RMIB I ) Pesticide Reevaluation Division (PRO) (7508P)

As part of Registration Review, the Pesticide Reevaluation Division ( PRO ) has requested that the Health Effects Division (HE D ) provide a human health ri sk assessment sco pin g document for the rodenticide agent diphacinone and diphacinone sod ium sa lt. The most recent risk assessment for diphacinone was conducted in April 9

, 1997 ( M e mo , 

### J. R edde n, HED Chapter of the R eregis t rat ion El i g ibili ty D ec i sion D ocu m e nt (RED) for Diphacinone).

Page 1 of 32

### Exec utiv e S umma ry

HED has prepar e d a scop in g document to suppo rt Registration R ev i ew fo r diphacinone or (2- diphenylacetyl-1

, 3 -in dandione ) a nd diphacinon e sodium sa lt. Diphacinone i s a first generat i o n anticoagulant rodenticide that acts by inhibitin g the enzyme v itamin K epox i de reductase w hich i s a c rucial component in a number of normal clotting factors. Diph acinone i s re g i s ter ed to 

### control hou se mice

, a var i ety of r ats , squ irrel s. and vo le s inside and within 1 00 feet of man-made
st

ru ctures, in agricultural fields

, orchards and the sub terr a nean control of m o l es and gophers

arou n d lawns

, go l f courses, and o th er turf areas. There a r e over 50 diphacinone end-use products

co mpri se d of 0.005 

### %

- 0.2 

### % active in gre dien t (a i ) formulated as cakes

, liquid concentrate, meal bait, paraffi ni zed pe ll ets, paraffin blocks

, ready-to-u se place pack s, s l abs, and tracking powder. Produ c ts that are int ended primarily fo r occ up at ion al u se are packaged in 4 pounds o r more.

Diphacinone to xic it y is m a nif es t e d as an incr ease in prothrombin and partia l thromboplast i n tim e. S i gns of toxicity in c lu de dyspnea

, lethar gy, he morrha ge from th e nose , and uterin e bleeding. Death follows excessive external and/or internal bleeding. Technical grade diphac i none h as high acu t e to xic it y 

### via oral

, dermaL and inh a l at i on routes of ex po s ure (Tox icity Ca te go r y 1 ). It i s a non-irritant to th e s kin (Ca t ego r y IV ) and moderate irritant to the eye (Ca t egory lIJ ). Diphacinone is not a dermal sens iti ze r. T h ere is no cance r c l assifica ti o n for di phaci non e.

To evaluate t h e scope of work nece ssary to support Regi s tration R ev iew

, H ED ha s considered

r ece nt ri sk assessments for diphacinone and it s sod ium salt, updat es to its toxicity

, exposure, and
usage dat abases

, and the l atest Agency scie n ce policy and ri sk assessment m e thodolo g i es

.

T h e toxicology database fo r diphac i none i s adeq uat e for risk assessme nt of r egistere d u ses

. The toxicology s tudi es ava il able in c lud e : a 21-day de rm a l in rabbits, 2 1-da y ora l in mi ce, acu te
t ox icit y in rats , 14

- day r epeat dose in rat s

. developmental to x i c i ty in rats , mut age ni c i ty battery.

a nd a met a boli s m study in rats. There are no chronic and / or carc in oge ni c i ty s tudi es on di ph ac i none. Given the ex clu sive l y non-food u ses c hr o ni c and/or carci n oge nici ty stu di es are not

r eq uir e d. Ad diti o nall y, th e avai l able muta ge ni ci t y s tudi es s h owed that there i s no muta ge ni c it y

c onc ern . B ased on a weight of evide nc e approac h conside rin g a ll the ava il ab l e hazard and
exposure in forn1atio n , H E D 's HASPOC determined that the s ubchronic inhal at ion toxi c it y st ud y, developm e ntal toxicit y s tud y in rabbit s reproduction

, neurotoxic i ty and immunot ox icit y studies

are not r equi r ed (U

. Habib a, T X R 0057326, 1 2/15 / 20 15 ). At the time of Re g i strat i o n R ev i ew th e Age n cy ma y updat e points of d e parture s ( POD s) and toxicolo g ical e ndp o int s based o n upd ated policies for occupational a nd residential ex p osu re assessme nt s as we ll as t h e potentia l for drinking water expos ure. Additio n a ll y, th e unc e rt ainty fac tor s will be r eassesse d in the co nt ex t of the updat ed PODs and endpo i nts.

In th e pre v iou s 1 997 assessment di etary food and drinking wa t e r exposures were not quantified becau se of th e limit ed non-food u se pattern and the Food Qualit y Prote c tion Ac t (F QPA)

co n s i deration s did n ot apply. T her efo r e an a gg r ega t e risk assessment was not conducted in 1 997. While the dietary food r e main s n ot a c o n ce rn for H ED, the r egiste red aerial ag ricultural broadcas t app li cat i ons to post-harv es t orchard s and nur se r1e s may indu ce consideration of drinking water es tim ates dur in g the Regi s tration Review process. I l oweve r it is noted that the

P age 2 of 32

### Page 3 of 32

application rate is considerably low ( maximum single aerial application rate is 20 pounds of product per acre or 1.03 E

- 03 pounds of active ingredient per acre )

. A short term dermal and inhalation occupational and residential handler exposure assessment will be required during Registration Review based on the potential exposure to handlers (mixers, loaders, applicator, etc.) during the use of pelleted, liquid conce ntrate, and dust formulations of diphacinone. E xposure to products formulated as bait cakes, blocks, s achets, and disposable bait stations is considered to be negligible. Occupational post

- application exposure is not expected due unlikely hood of reentry to the use sites (r esidential structures, post

- harvest agricultural fields

, etc.)

. Re sidential p ost

- application exposure is not anticipated as product s must be tamper resistant packaging if used above ground. The one exception of this is product formula ted as a tracking powder (EPA Reg #12455

- 56) which is applied indoors in residential setting s

. Post

application incidental ingestion exposure for t he tracking powder formulation should be assessed during Registration Review

. Th ere have been recent change s in assessment assumptions, including body weight, amount tre ated, and transfer coefficients th at will need to be incorporated into exposure assessments during Registration Review along with any changes to reevaluate the points of departure , toxicity endpoints, and uncertainty factors u sed for risk assessment purposes

. Spray drift exposure is not anticipated for the current diphacinone use pattern

, however t he Agency will examine the need for spray drift and volatilization assessments duri ng Registration based on the potential for exposure to bystanders from agricultural applications.

I ntroduction

Diphacinone (2

- diphenylacetyl

- 1,3

- indandione) is a rodent control agent registered for the control of rodents in and around farm structures, households, and domestic dwellings, uncultivated agricultural and nonagricultural areas, commercial transportation facilities, industrial areas, in sewage systems, aircraft, ships, boats, railway cars, and food processing, handling, and storage areas and f acilities. The anticoagulant is formulated as meal bait s , tracki ng powder, concentrate s , paraffinized pellets, ready

- to

- use place packs, paraffin blocks, cakes, and slabs. All products are 0.005 percent active ingredient, with the exception of three form ulations: (1) Ditrac Tracking Powder, which is 0.2% active ingredient, (2) Contrax

- P Cakes, which are 0.025% active ingredient, and (3) Diphacinone concentrate, which is 0.1% active ingredient. The most recent human health risk assessment was finalized in April 2007 (Memo, J. Redden to L. Rossi, and “ HED Chapter of the Reregistration Eligibility Decision Document (RED) for Diphacinone”).

In 2008, the Agency issued a risk mitigation decision for ten rodenticides, of which diphacinone was included. The mitigation decision set restrictions in order to minimize exposure to children, wildlife and domestic animals. The risk mitigation decision is summarized below and does not apply to rodenticide field (non

- commensal rodents) uses or tracking powder pr oducts.

 Consumer

- based products (≤ 1 pounds ),

o Second

- generation anticoagulants are prohibited as well as loose baits/pellets/meal as a form for above ground outdoor uses.

### Page 4 of 32 o 

### When applied outdoors above ground and in areas accessible to children,

non

- target w ildlife or domestic animals, baits must be contained in bait stations.

o 

### Products for use outdoors and above

- ground must be placed within 50 feet of a building.

 

### Professional

- based products

,
o 

### Must be sold in quantities of ≥ 4 pounds (first

- generation antic oagulants/non

- anticoagulants), ≥ 8 pounds (second

- generation anticoagulants; agric ultural building use) and ≥ 16 pounds (second generation anticoagulants; above ground outdoor use)

.
o 

### May not be offered for sale in consumer stores (hardware, grocery, etc.).

o 

### Must also be placed within 100 feet of a structure (fence and perimeter baiting beyond 100’ of a man

- made structure are prohibited) when used outdoors and above ground, see 50 foot Document Clarification Letter to Bell (03.20.12) (signed) in docket number EPA

- HQ

- OPP

- 2006

- 0955

- 0820 found at www.regulations.gov.

o 

### For uses of first

- generation or non

- anticoagulants, product labels require bait stations if children, wildlife or domestic animals may be exposed.

o 

### For uses of second

- generation anticoagulants, labels require bait stations for all outdoors above grounds placements and/or indoor placements where children, wildlife or domestic animals may be exposed.

Several of the diphacinone products are currently registered as restricted use pesticide s (RUP s ). Product s intended for occupational use are packaged as 4 pounds (lbs

. ) or more. The majority of dipha cinone products are applied using tamper resistant bait stations, which are required for all rodenticides where children and pets may be present per 2008 anticoagulant rodenticide mitigation. There are

, however

, some diphacinone end use products tha t are applied with aerial, and ground broadcast equipment at a maximum rate of 20 lb s. of product per acre or 1.03 E

- 03 lb s. active ingredient per acre in post

- harvest fruit tree orchards and commercial nurseries. In addition

, tamper resistant bait stations are not required for burrow, canopy , and tracking powder application s

. See preliminary use profile table in the a ppendix (A ttachment 3) for more information on application rate and application methods of diphacinone products

. Hazard Identification/Toxicology

Diphacinone is an anticoagulant rodenticide with terrestrial and residential non

- food uses. Technical grade diphacinone has high acute toxicity via oral, dermal, and inhalation routes of exposure (Toxicity Category I). It is a non

- irritant to the skin (Category IV) and moderate irritant to the eye (Category III). Diphacinone is not a dermal sensitizer

. At present, the available toxicological databa se for diphacinone is adequate and will support a reregistrat ion eligibility determination.

The toxicology studies available include: a 21

- day dermal in rabbits, 21

- day oral in mice, acute toxicity in rats, 14

- day repeat dose in rats, developmental toxici ty in rats, mutagenicity battery, and a metabolism study in rats. A 2

- generation reproduction toxicity study is not required for diphacinone

. C hronic and/or carcinogenicity studies are not required g iven the exclusively non

-

### Page 5 of 32

food use pattern. The availab le mutagenicity studies show no mutagenicity concern. There was no susceptibility seen in the developmental study. B ased on a weight of evidence approach considering all the available hazard and exposure information, HED determined that the following stu dies were not required: subchronic inhalation toxicity study , developmental toxicity study in rabbits , reproduction, acute and subchronic neurotoxi city, and immunotoxicity ( U. Habiba , TXR 0057326, 12/1 5 /2015 )

. Diphacinone toxicity is manifested as an increase in prothrombin and partial thromboplastin time. Signs of toxicity include dyspnea, lethargy, hemorrhage from the nose, and uterine bleeding. Death follows excessive external and/or internal bleeding. A 14

- day repeated dose toxicity study in Spr ague Dawley rats was conducted specifically to identify effects on clotting factors and overt signs of toxicity or lethality associated with anticoagulant effects following single and repeated dosage with technical diphacinone. In this study, a no observe d adverse effect level ( NOAEL ) of 0.085 mg/kg/day was reported based on decreased prothrombin and activated partial thromboplastin times at the lowest observed adverse effect level ( LOAEL ) of 0.175 mg/kg/day following repeated exposure. The NOAEL of 0.085 mg/kg/day was selected for assessment of risk via inhalation exposure as no route

- specific study was available. For dermal exposures, a NOAEL of 0.10 mg/kg/day was selected from the 21

- day dermal study in rabbits based on clinical signs consistent with a nti

- coagulant effects at the LOAEL of 1 mg/kg/day.

At the time of Registration Review the Agency may update PODs and toxicological endpoints since they are considered conservative based on updated policies for endpoint selection. Additionally, the uncertainty factors will be reassessed in the context of the updated PODs and endpoints. Please refer to Attachment 4 for a summary of the toxicity endpoints and points of PODs and Attachment 6 for the c omplete toxicity profile table.

Conclusions : The toxicology database for diphacinone is adequate for risk assessment of the
current uses. At the time of Registration Review, the Agency may update PODs and toxicological endpoints since they are considered conservative based on updated p olicies for endpoint selection. Additionally, the uncertainty factors and the need for a dietary endpoint based on water only will be reassessed in the context of the updated PODs and policies

. Residue Chemistry and Dietary Exposure

All uses of diphacin one are non

- food uses; therefore, no tolerances are established or needed. In addition, a dietary exposure assessment from food is not needed. However, the broadcast applications to orchards may result in the need for a drinking water assessment in Regis tration Review.

Conclusions : A new dietary exposure assessment is not anticipated to be needed during Registration Review unless there are drinking water exposure estimates.

### Page 6 of 32

Residential Exposure

Residential Handler Exposure Diphacinone is currently registered for use to control rats, mice, and squirrels in residential settings including in and around homes as well subterranean control of gophers and moles in gardens and turf . Residential handler exposure from handling tamper resistant b ait stations loaded with non

- dusty formulations such as sachets, bait cakes , and paraffinized pellets is considered to be negligible. There is however anticipated handler dermal an d inhalation exposure from hand dispersal (i ncluding cup and spoon ) of non

- paraffinized products such as meal or grain

- based baits for the subterranean control of moles and gophers.

Residential Post

- Application Exposure Post

- application exposure to products placed in t amper resistant bait stations or below ground are not antic ipated. Tamper resistant b ait stations are mandatory for any bait placed above ground where childr en and/or pets may be present with the exception of t racking powder products

. T herefore an episodic ingestion assessment may be necessary during Registration Review

Non Occupational Spray Drift or Volatilization Residential bystander exposures resulting from off

- site transport (i.e., spray drift or volatilization) is unlikely due to how diphacinone is formulated and used except for the granular broadcast applications of diphacinone in commercial orchards and nurseries [(and others as appropriate)]. The approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

– Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This guidance indicates that drift is not a concern when solid materials are applied (e.g., by aerial equipment). Therefore, only the potential for volatilization will be evaluated for each p esticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. In terms of volatilization, the agency has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registration Review, the Agency will utilize this analysis to determine if data ( e.g. flux studies, route

- specific inhalation toxicological studies) or further analysis is required for diphacinone.

Conclusions: A residential handler assessment is required during Registration Review. An episodic incidental oral post

- application assessmen t for tracking powder formulated products may be needed during Registration Review

. T he Agency will examine the need for a volatilization assessment, as well as evaluate the potential diphacinone exposure from spray drift during Registration Review.

Aggr egate Risk Assessment

In accordance with the Food Quality Protection Act , HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. Diphacinone is registered for non

- food uses, however water exposure may be a possibility due to the aerial and ground applications in agricultural settings

. For adults, the pathways leading to
exposure remain residential handler dermal and inhala tion exposure from handling non

-

### Page 7 of 32

paraffini zed products for subterranean control . Residential handler exposure and quantitative drinking water estimates for diphacinone may be aggregated if deemed appropriate at the time of Registration Review

. A n aggregate ris k assessment of any duration is not anticipated for children unless it is determined that an episodic incidental oral post

- application assessment is needed for tracking powder formulations.

Conclusions : If computing drinking water estimates is deemed a ppropriate from the aerial agricultural uses of diphacinone then a short term adult a ggregate assessment is expected during the Registration Review, unle ss changes in use pattern or updated procedures occur.

Occupational Exposure

In the previous 1997 assessment HED had concern s about the risks to handlers of diphacinone products, particularly commercial handlers with the (1) handling large quantities of product, (2) handling dusty, non

- paraffinized products and (3) applying product s by hand. However

e xposure and r isk estimates were not identified due to lack of unit exposure data available at the time. In 2007, the ready to use (RTU ) pelleted product, Kaput Field Rodent Bait B Registration # 72500

- 11 was assessed for ST and IT occ upational handler dermal exposure (M. Dow, D338351, 04/09/2007 ). Based on this assessment HED recommended requiring commercial handlers to wear waterproof gloves while handling all diphacinone formulations that are not contained in a tamper

- resistant ba it stations or in place d packs

. Diphacinone labels reflect this mitigation requirement.

O ccupational Handler Exposure Occupational handlers are anticipated to have short

- and intermediate

- term dermal and inhalation
exposures from mixing, loading, and applyi ng the liquid concentrate s on grain bait , loading and applying pelleted and impregnated grain bait products by aerial, ground, and handheld equipment , and applying the tracking powder formulation

. Occupational dermal and inhalation exposure to reloading b ait cakes, bait sachets, and disposable bait stations is considered to be negligible. Long

- term occupational exposure is not expected. The registered end use diphacinone products require occupational handlers to wear long sleeved shirts, long pants, shoes, socks, and water proof gloves with the exception of pre

- filled bait stations

. Diphacin 110 concentrate (REG # 61282

- 43) requires mixers and loaders to wear a dust mist filterin g respirator protection. U pdated occupational exposure assessment policies and body weight assumptions will be incorporated into diphacinone exposure assessments for Registration Review. In addition inhalation margins of exposure will be included in the Registration Review of diphacinone and its sodium salt.

Occupational Post

- Application Exposure There is no anticipated occupational post

- application exposure to the current use pattern of diphacinone and diphacinone salt. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for diphacinone

.

Conclusions : There is sufficient information available to assess occupational handler exposures however mo re information on use pattern and maximum application rate for products that are not

### Page 8 of 32

placed in a tamper resistant packaging would refine the assessment. Updated occupational handler exposure assessments will be conducted during Registration Review. Occup ational post

application exposure is not anticipated for Registration Review.

Public Health and Pesticide Epidemiology Data

As part of the Rodenticide Risk Mitigation Decision (RMD), and the subsequent Notice of Intent to Cancel (NOIC), the Environmental Protection Agency’s Office of Pesticide Programs’ Pesticide Re

- evaluation Division requested an analysis of human incidents i nvolving exposure to rodenticides in 2011 (S. Recore, D395567 , 10/28/2011 ) and then updated in 2015 ( S. Recore, D426573, 11/24/2015 )

. S ummary report listing incidents for diphacinone and diphacinone sodium salt are reported to the OPP Incident Data System (IDS), the National Pesticide Information Center ( NPIC ), the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH), Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) , and Ag ricultural Health Study (AHS) databases

. In order to minimize children and wildlife exposure to rodenticide products the 2008 RMD included risk mitigation measures requiring rodenticide products used in homes and marketed to general residential consumers be sold only with bait stations. Most rodenticide products complied with the mitigation measures required in the RMD as of June 4, 2011. The phase out production of the final 12 non

- compliant products began in June 2014 and production of these products stopped on December 31, 2014. Distribution to retailers ended March 31, 2015.

Due to the fact that these safety measures were only recently fully implemented, there is insufficient information available, at the time of this report, to determine if the mit igations have impacted the frequency of incidents occurring. However; AAPCC data is reviewed annually for reduction in reported rodenticide incidents as a Strategic Measure. For FY 2014 (using the 2013 AAPCC annual report data), there was a reduction of 17% incidents reported to the AAPCC annual reports compared to the number of rodenticide exposures to children ages 1 to 6 years old in 2011. The reductions in child exposures are expected to become more prominent beginning in the 2016 AAPCC annual report ; which will be reflected in the FY 2018 Strategic Measure. The target reduction for FY 2018 is to reduce rodenticide exposure incidents by 75% compared to a baseline measure of 11,674 reported incidents in 2008 in children ages 1 to 6 years old.

The Agen cy will continue to monitor the incident information and provide an updated review of incident, considering pre

- and post

- mitigation incidents separately, when the information becomes available.

Tolerance Assessment and International Harmonization

There a re no tolerances for diphacinone and diphacinone sodium sa lt as it is a non

- food use.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions

### Page 9 of 32

to Address Environmental Justice in Minority Populations and Lo w

- Income Populations," http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf

. As a part of every pesticide risk ass essment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to pesticide exposures that are based on activities in and around the home that involve pesticide use in a residential setting. Whenever appropriate, these non

- dietary exposures are calculated based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- applica tion are evaluated.

Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as
to diphacinone and any other substances and di phacinone does not appear to produce a toxic metabolite produced by other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see th e policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Human Studies

The risk assessments which have been previously conducted for diphacinone rel ied in part on data from studies in which adult human subjects were intentionally exposed to a pesti cide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural Handler Exp osure Task Force (AHETF) database, and the Outdoor Residential Exposure Task Force (ORETF)

. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of an y of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued reliance on these studies

.

Data Deficiencies

No toxicological, residue chemistry, or occupational and residential exposure data are needed to support the registered uses of diphacinone at this time, however more information on use pattern and maximum application rate for products that are not placed in a tamper resistant packaging including the tracking powder formulations would refine the assessment.

### Page 10 of 3 2

References

Recent Mem oranda Relevant to Registration Review of Diphacinone

Author DP/TXR # Date Title

Risk Assessment

J. Redden Not available April 9, 1997 HED Chapter of the Reregistration Eligibility Decision Document (RED) for Diphacinone

. Not available May 28, 2008 (revised June 24, 2008) Risk Mitigation Decision for Ten Rodenticides

.

U. Habiba TXR 0057326 December 15, 2015 Rodenticides: Summary of Hazard and Science Policy Council (HASPOC) Meeting on October 1, 2015: Recommendations on Data Requirements for Rodenticides. Occupational and Residential Exposure Assessment

M. Dow D338351 April 9, 2007 Diphacinone/Imidacloprid

- Human, Non

- dietary Exposure/Risk Assessment for the Proposed Use of Diphacinone and Imidacloprid as a “Rodent, Rabbit and Flea Control Bait”.

T. Campbell D231606 December 23, 1996 O ccupational and residential exposure assessment and recommendations for the reregistration eligibility decision document for diphacinone. Incident Report

S

. Recore D 395567 October 28, 2011 Rodenticides Tier II : Review of Human Incidents

.

D 426573, D42673 November 24, 2015 Rodenticide: Tier I (Scoping) Review of Human Incidents and Epidemiology Assessment

.



### Attachments

1. Chemical Identity Table 2. Physicochemical Properties of Technical Grade Diphacinone Table 3. Use Profile Table for Diphacinone. 4 . Endpoint Selection Table s 5. Toxicology Data Requirements 6 . Toxicity Profile Tables

### Page 11 of 32

Attachment 1

Chemical Identity Table

Table A.1: Diphacinon e Nomenclature
Chemical structure

C 23 H 16 O
Common name Diphacinone Company experimental name
IUPAC name ( 2

- (diphenylacetyl)indan

- 1,3

- dione
CAS name ( 2

- (diphenylacetyl)

- 1 H

- indene

- 1,3(2 H )

- dione CAS registry number 82

- 66

- 6
Chemical structure of diphacinone sodium salt

C 23 H 15 NaO 3 IUPAC name of Sodium Salt sodium;2

- (2,2

- diphenylacetyl)inden

- 2

- ide

- 1,3

- dione

### Page 12 of 32

Attachment 2

Physicochemical Properties of Technical Grade Triticonazole Tabl e

Table A.2: Physicochemical Properties of the Technical Grade Diphacinone

Parameter Value Reference
Melting point (°C) 146 oC; PAI displays two crystalline forms melting at 137 and 141 oC

The Pesticide properties Database: http://sitem.herts.ac.uk/aeru/iupac/i

ndex.htm pH Not available

Density at 20 °C (g ml

- 1 )/ 1.28 (g ml

- 1 )

Water solubility (at 20 °C) (mg l

- 1 ) 0.3 at 20 o C (mg l

- 1 )

Solvent solubility (at 20°C) (mg l

1 ) Solvent Solubility (g/L)
C4

- Acetone C4

- Ethanol C4

- Heptane C4

- Xylene 22900

16800 1224 43000
Vapor pressure at 25°C 1.37 X 10

- 05 at 25 o C (mPa)

Dissociation constant (pK a ) Not available Note: Acidic

Octanol/water partition coefficient 4.85 pH 7, 20 o C Log P

UV/visible absorption spectrum Not available

### Page 13 of 32

Attachment 3. Preliminary Use Profile Table for Diphacinone

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

BELL LABORATO RIES, INC 3699 KINSMAN BLVD MADISON WI 53704 608/241

- 0202 LIQUA

- TOX

II EPA Registration Number: 1245 5

- 61 0.106%

(Dipha cinone Sodium Salt) Concentrate

in Pouch 8

- 50

pouches containing 1.68 fl. Oz pouches

Norway

Rat, roof rat and house mice. Yes 1.11E

- 0 4 lb ai/ stations with 50 stations

Rats : 16 oz. of diluted product in each stations

. Mice: 8 oz. of diluted product in each station

SL/G No Do Not Use in Homes or Other Residential Settings For indoor use only inside of industrial, commercial, agricultural, and public buildings, and similar man

- made structures. Do Not Use Outdoors or in sewers. Do not sell this product in individual containers holding less than 13.44 fl. oz. of bait concentrate. Mix 1.68 fl. oz. pouch in 1 quart (32 fluid ounces) of water.

J.T. EATON & CO., INC. 1393 E. HIGHLAND ROAD TWINSBU RG OH 440 87 800/321

- 3421 BAIT BLOCK

RODENTICID E WITH PEANUT BUTTER FLAVORIZE R EPA Registration Number: 56

- 42

0.005

% Bait Block 4 to 50 lbs

32 X 2 oz. to 400 X 2 oz. Bait Blocks Rats: 2 to 8 (2 oz. blocks) or 4 to 16 oz. with 15 to 30 feet intervals. 5.00E

- 05lb ai/station or 0.0025 lb ai/50 lb bag. Mice: Break one 2 oz. block into 3 pieces and place 1 or 2 pieces at 8 to 10 feet intervals. Use within 100 feet of man

- made structures. Do not sell less than 4 pounds of bait. Burrow baiting is prohibited. Do not use in sewer. Do not broadcast. Fence and perimeter baiting beyond 100 feet from structure is prohibited. APPLE BAIT BLOCK RODENTICID E EPA Registration Number: 56

- 74 EATON'S ANSWER FOR THE CONTROL OF POCKET GOPHERS EPA Registration Number: 56

- 57 10, 12, 50 lb. Commercia l Use Gophers No (below ground applicati on) Gopher: Probe 12 to 18 inches from surface to mound and place one bait block at two or three location in each main burrow (runway) system. Subterranean control of gophers in rangeland, cropland, (grain fields, forage corps, hay and alfalfa crops and vegetable c rops), forest and non

- crop areas including park, nurseries, and around homes. Do not apply this product above ground. Do not mechanically apply. 1 pound Intended for residential

use

### Page 14 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

RECKITT BENCKISER LLC D/B/A RECKITT BENCKISER 399 INTERPACE PARKWAY PARSIPPA NY NJ 0705 4 973/404

- 2716 D

- CON BAIT

STATION X EPA Registration Number: 3282

- 98

0.005

% Prefilled disposable bait block stations Prefilled

disposable bait stations. Block formulatio

n Indoor

Mouse Control

Yes Remove the bait station

from carton and place along wall or in corners. Place bait stations 8 to 12 foot intervals. For use to control house mice for indoors only Do not use outdoors or in areas accessible to pets and children. This is a not a refillable container D

- CON BAIT STATION IX EPA Registration Number: 3282

- 99 D

- CON BAIT STATION XIV EPA Registration Number: 3282

- 100

Bait blocks 1

- 2 disposable bait stations with one 1.0 oz. block. (1

- 2) oz. (28 g) per bait Indoor

and Outdoor Mouse For use to control mice within 50 feet of homes accessible to children and pets indoors and outdoors. Do not apply where possibility of contaminating food or food surfaces. D

- CON BAIT STATION XIII EPA Registration Number: 3282

- 101 D

- CON BAIT STATION XI KILLS MICE EPA Registration Number: 3282

- 102 1

- 2 refillable bait station and 1

- 2 refills (blocks) each 1.0 oz. Block D

- CON BAIT STATION XII EPA Registration Number: 3282

- 103

### Page 15 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

RCO INTERNATI ONAL INC. D/B/A RCO INTL. INC. PO BOX 191 HARRISB URG OR 97 446 800/214

- 2248 RCO MOLE &

GOPHER PATROL BAIT EPA Registration Number: 5042

- 33 1

0.005

% Pelleted Commercia

l size: 4

- 25 lb

Moles and

pocket around lawns, golf
course, and other turf areas No

(below ground applicati ons) Moles : Deposit a

teaspoon quantity about 4 grams of bait through the hole. Bait each active subsurface at 10

- 15 foot intervals. Gopher: Apply 1⁄2 cup of bait down enlarged hole. Make 2

- 3 application per active burrow system. Also can use a buried bait station with 1 lb SL/G No Do not apply bait above ground. Bait must be applied directly into mole and pocket gopher burrow system. Store out of reach of children and pets. Do not apply directly to water. Do not contaminate food o r food surfaces. Residential

: 8 oz. and 1lb

RCO PATROL BURROW BUILDER BAIT FOR MOLES & GOPHERS EPA Registration Number: 5042

- 35 10

- 50 lb Manual App. Moles : 4 grams bait in top of runway. Mechanical App. Construct artificial burrows treat at 6

- 8 lb/A

. or 4.0E

- 4 lb ai/acre Yes On lawns, golf courses, and sod farms in and bordering crop, rangeland fruit orchard, and non

- crop areas. Do not apply bait above ground. Do use within prairie dog and active dens of San Joaquin Fox. Do not contaminate food or surfaces that come into contact with food.

BELL LABORATO RIES, INC 3699 KINSMAN BLVD MADISON WI 53704 608/241

- 0202 DITRAC

ALL

WEATHER CAKE EPA Registration Number: 1245 5

- 5 0.005

% Cake 4

- 50 lbs. Cake consists of 1 lb slab scored into 16 one oz. pieces. Rats,

mice, and meadow voles Yes Rats: 4 to 16 pieces of

bait at 15 to 30 feet interval. Mice/Voles : one 1 oz. piece per bait placement at 8 to 12 foot interval. SL/G No This product May Only b e Used Inside and Within 100 Feet of Man

- made Structures. Burrow baiting prohibited. Not permitted for use against the following species in California: Cotton rat, Eastern harvest mouse, Golden mouse, Polynesian rat, Meadow vole, White

- throated woodrat, So uthern plains woodrat, and Mexican woodrat DIPHACINO NE CONCENTRA TE EPA Registration 0.1 % Concentrate 25 lbs Rats and Mice Only use to make formulated products in and around structures and inside transport vehicles (ships, trains, and aircraft ).

### Page 16 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

Number: 12455

- 9

DITRAC SUPER

- SIZE BLOX EPA Registration Number: 1245 5

- 14 0.005

%. Bait block 4

- 50 lbs.

Norway Rats, Roof Rats, Yes Use one bait block per

placement. Space placements 15 to 30 feet apart in infested areas. SL/G No This product May Only be Used Inside and Within 100 Feet of Man

- made Structures and sewers. Burrow baiting

prohibited.

TECHNICAL DIPHACINO NE EPA Registration Number: 1245 5

- 25 99.3% Concentrate 1 lb. Only for formul ation into registered products in an d around homes, industrial and agricultural buildings, similar man

- made structures; inside transport vehicles (ships, trains, aircraft), in and around related port or terminal buildings, and in alleys located in urban areas.

DITRAC TRACKING POWDER EPA Registration Number: 1245 5

- 56 0.2 % Powder 6

– 25 lb No Sprinkle 1⁄2 oz. (3 teaspoons) of powder in patches 12 inches long and 6 inches wide. 6.25E

- 05 lb ai/patch Burrows place 5 grams of tracking powder in each burrow with pump duster. SL/G Yes For use in doors and in burrows leading indoors. DITRAC TRACKING POWDER must be placed in locations inaccessible to children, pets, domestic animals, or wildlife.

DITRAC ALL

WEATHER BLOX EPA Registration Number: 1245 5

- 80 0.005

% Bait Block 4 lb (64 x 1

ox bait block) to 50 lb (800 x 1 oz. bait block) Rats,

Mice, and Meadow Voles. Yes Rats: Apply 3 to 16

ounces. Place 15 to 30 feet for 10 days. Baiting sewers : Use 3 to 16 blocks per manhole. Mice and Meadow Voles : Apply 1 block per infested area at 8

- 12 foot intervals. SL/G No This Product May Only be Used Inside and Within 100 Feet of Man

- Made Structures

. Not permitted for use against the following species in California: Cotton rat, Eastern harvest mouse, Golden mouse, Polynesian rat, Meadow vole, White

- throa ted woodrat, Southern plains woodrat, and Mexican woodrat. Burrow baiting with Ditrac. Do not broadcast. DITRAC RODENTICID E Pelleted 4

- 50 lb RATS : Apply 4 to 16 oz. of bait (usually at intervals of 15 to 30 feet)

### Page 17 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

EPA Registration Number: 1245 5

- 81 per placement in infested

areas. 5.00E

- 05lb ai/station or 0.0025 lb ai/50 lb bag. MICE: Apply 1/4 to 1/2 oz. (1 to 2 level tablespoons) of bait at 8 to 12 foot intervals in infested areas. ( Up to 2 oz.). DITRAC RODENTICID E PLACE PAC EPA Registration Number: 1245 5

- 83 Sachet (packets) 4 lb (22 x 3

oz. place pacs) to 50 lb (267 X 3 oz. place pacs) Rats and

Mice Rats: Place 1 to 5 place

packs (3 to 15 oz. ) at 15 to 30 foot intervals. Mice : 1⁄4 to 1⁄2 oz. (1

- 3 level tablespoons) of bait at 8 to 12 foot inte rvals. SL/G No This Product May Only be Used Inside and Within 100 Feet of Man

- Made Structure. Burrow baiting prohibited. Do not broadcast bait. Do not sell this product holding less than 4 pounds of bait.

TOMCAT MOUSE KILLER VI EPA Registration Number: 1245 5

- 119

0.005

% Bait Block 4 oz.

(112g) 4 x 1 block bait & refillable bait station Mice

Yes Mice: One block bait in one bait station. Place bait station s 8 to 12 foot interval and maintain for 15 days. SL/G No For use indoors and outdoors. This bait station may be used in an around (within 50 feet of) manmade structures. For control of house mice only. This bait station can only be refilled with the block bait sold with this station. TOMCAT MOUSE KILLER V EP A Registration Number: 1245 5

- 126 1 disposable bait station 1 x 1 oz. (28 g) bait block. Up to 16 disposable bait stations containing 12 X 1 oz. (28 g ) bait blocks TOMCAT MOUSE KILLER VII EPA Registration Number: 1245 5

- 127 House Mice For use indoors only.

### Page 18 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

TOMCAT MOUSE KILLER IX EPA Registration Number: 1245 5

- 128 No

TOMCAT MOUSE KILLER VIII EPA Registration Number: 1245 5

- 130

0.005

%i 4 oz.

(112g) 4 x 1 oz. block bait & bait station

– 16 oz. (454g) 16 x 1 block bait & refillable bait station. Yes

PCQ Rodent Bait EPA Registration Number: 1245 5

- 136 Pelleted. 4 to 50 lbs. Norway rats, roof rats, and house mice Yes Rats: Place 4 to 16 oz. at

15 to 30 foot intervals and maintain for 10 days. 4.0E

- 04 lb ai/patch Mice: Open pac and apply 1⁄4 to 1⁄2 oz. (1

- 3 level tablespoons) of bait at 8 to 12 foot intervals infested areas. 1.56 E

- 06 lb ai/patch

SL/G Yes Use within 100 feet of man

- made structures. Do not sell this product in individual containers holding less than 4 p ounds of bait.

Commerc ial Nurseries: Meadow and Pine Voles No Hand Baiting: l/2 oz. (2

tablespoons) into each tree site ( 10 lb product per acre). 5.0E

- 04 lb ai/acre or 1.56E

- 05 lb ai/patch BAIT STATIONS: Place 2 Ib. bait station GROUND BROADCAST Hand and Spreader : Apply 10 Ib. per acre. For pine vole application For control of meadow and pine voles in commercial nurseries in the following stat es: Georgia, Michigan, Missouri, North Carolina, and South Carolina. Do not apply by aerial application. Do not apply this product in a way that will contact workers or other persons, either directly or through drift.

### Page 19 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

in states east of the Mississippi River, a rate of 20 Ib. per acre may be required. 1.0E

- 03 lb ai/acre

Commerc ial Fruit Trees Orchards (Dormant ) Voles Yes/No HAND BAITING: Place

l/2 oz. (2 tablespoons) at each tree site (10 lb. per acre). BAIT STATIONS : Place 2 Ib. of bait in a tamper

resistant bait station in areas frequented by voles (near surface trail s and burrows). GROUND BROADCAST: Apply 10 lb. per acre. 5.0E

- 04 lb ai/acre Do not graze animals in treated areas. For use in Connecticut, Georgia, Idaho/aerial, Massachusetts, Michigan/aerial, Missouri, Montana/aerial, North Carolina, New Hampshire, Oh io (aerial), Oregon/aerial, Pennsylvania/aerial, South Carolina, Utah/aerial, Virginia/aerial, Vermont/aerial, Washington/aerial, and West Virginia/aerial.

Tomcat Ground Squirrel Bait EPA Registration Number: 1245 5

- 145 0.005

% Pelleted 4 to 50 lb California ground Squirrel Yes 2 to 4 lb of bait per

station. 2.0E

- 04 lb ai/1 station or 0.01 lb ai/50 lb bag No This Product May Only be Used Within 100 Feet of Man

- made Structures to Control California Ground Squirrels

WILCO DISTRIBUT ORS, INC. PO BOX 291 LOMPOC CA 93438 805/735

- 2476 GROUND

SQUIRREL BAIT BY WILCO AG EPA Registration Number: 3602 9

- 17 0.005

% Pelleted 20 lbs and

40 lbs. California

Ground Squirrel Yes 2 to 4 lbs of bait per

station. 2.0E

- 04 lb ai/1 station Yes For use in building in non

- crop areas, along fence lines. In rangeland and pasture land and in crop areas such as

orchards.

GROUND SQUIRREL BAIT BY WILCO EPA 4 lbs No For use around building including yards, and flower beds.

### Page 20 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

Registration Number: 3602 9

- 20 GOPHER GETTER TYPE 2 AG BAIT BY WILCO EPA Registration Number: 36029

- 23 1

- 50 lb (1 lb container) hand probe unit

Gophers No

(below ground applicati on) 1 lb with 2

- 7 bait sets per

burrow SL/G Yes

For control of pocket gophers in crop and non

- crop areas. Subsoil application. Do not broadcast. GOPHER GETTER TYPE 2 BAIT BY WILCO EPA Registration Number: 3602 9

- 24 25

- 50 lb 1⁄2 cup product/burrow. Make 2

- 3 applications per burrow system. 1.25E

- 05 lb ai/burrow or 6.25 E

- 04 lb ai/50 bag SL/G No

U.S. DEPARTME NT OF AGRICULT URE ANIMAL AND PLANT HEALTH INSPECTIO N SERVI 4700 RIVER ROAD, UNIT 149 RIVERDA LE MD 207 37 DIPHACINO

NE

- 50: CONSERVAT ION PELLETED RODENTICID E B AIT FOR CONSERVAT IO EPA Registration Number: 5622 8

- 35 0.005

% Pelleted 20

- 50 lbs Norway rats, roof

ra ts, Polynesia n rats, house mice Yes Rats : Apply 4 to 16

ounces (113 to 454 grams) of bail per placement at 5 to 50 meters intervals. Mice: Apply 7 to 14 grams of bait per placement with 2 to 4 meters intervals . 5.0E

- 05 lb ai/station SL/G Yes For retail sale only to: USDA Animal and Plant Health Inspection Service Wildlife Services, U.S. Fish and Wildlife Service, and the U.S. National Park S ervice.

Burrow baiting No

( below ground applicati on) Rats: place 3 to 4 ounces (85 to 113 g) of bait inside each burrow
entrance. Mice: 0.25 ounces of bait in each active burrow. Baits used in burrows may be applied in piles or in cloth or plastic bags.

### Page 21 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

301/851

- 3885

Canopy Baiting No 4 to 7 ounces (113 g to

200 g) of bait should be placed in a cloth or re

sealable plastic bag at 50 meter intervals. The bags should be knotted or otherwise sealed to avoid spillage and holes should be made in plastic bags to allow the bait odor to escape. Using long poles (or other devices) or by hand, bait filled bags should be placed in the canopy of trees or shrubs bait placement in the canopy of trees and shrubs):

Aerial and Ground broadcast No Broadcast bait pellets by

helicopter or manually at a rate of 10 to 12.5 lbs. bait/acre. 6.25E

- 04 lb ai/acre

. A single application may be, made at a rate no higher than 20.0 lbs bait per/acre. 1 .03E

- 03 lb ai/acre Broadcast applications are prohibited

on vessels or in areas of human habitation. Aerial (helicopter) applications may not be made in winds higher than 35 mph (30 knots). Make a second broadcast application typically 5 to 7 days after the first application, depending upon local weather condition s,

61282 HACCO, INC. 110 HOPKINS DRIVE RANDOLP H WI 53956 920/326

- 5141 TECHNICAL

DIPHACINO NE EPA Registration Number: 6128 2

- 1 98.0% RODENTICIDE FOR FORMULATING USE ONLY. 110 pounds

DIPHACINO NE TECHNICAL GRADE EPA Registration Number: 6128 2

- 5 98.6% A Rodenticide only for Formulation into Registered Products

. Mixers must wear coveralls worn over short

- sleeved shirt and short

pants, chemical

- resistant footwear, socks, a dust/mist filtering respirator (MSHA/NIOSH approval number pr efix TC

- 21C), protective eyewear, and waterproof gloves. 1

- 50 pounds

PROMAR BAIT PACKS EPA Registration Number: 6128 2

- 6 0.005

% Pelleted readymade Bait Packs 4

- 60 lbs Rat and Mouse Yes RATS: Apply 2

- 8 bait

packs and at intervals of 15 to 30 feet in infested

areas. MICE: Open bait pack and apply 1⁄4 to 1⁄2 ounces SL/G NO This product may only be used inside and within 100 feet of buildings or inside of transport vehicles (ships, trains, o r aircraft). This Product May Not Be Sold in Packaging that Holds Less Than 4 Pounds of Bait. Each bait

### Page 22 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

RAT AND MOUSE KILLER BAIT PACK EPA Registration Number: 6128 2

- 9 0.005

% (1

- 2 level tablespoons) of bait at each at 8

- to 12

- foot intervals. pack is 2 ounces. Burrow baiting is prohibited

PROMAR BLOX ALL

WEATHER RODENTICID E EPA Registration Number: 6128 2

- 12 0.005

% a.i. 12 oz. block scored or 16

oz. block scored 4

- 36 lbs Yes RATS: Apply 4 to 16

one

- ounce Promar® Blox at intervals of 15 to 30 feet in infested areas. Or 5.0 E

- 05 lb ai/patch MICE: Break Promar® Blox into discrete 1

- ounce pieces. Apply one 1

- 2 ounce piece at 8

- to 12

- foot intervals. This product may only be used inside and within 100 feet of buildings or inside of transport vehicles (ships, trains, or aircraft). This Product May Not Be Sold in Packaging that Holds Less Than 4 Pounds of Bait. Burrow baiting is prohibited.

PROZAP MOUSE MAZE KILLS MICE EPA Registration Number: 6128 2

- 19 1

0.005

% a.i. 1 ounce of

bait per station 2

- 4 bait

preloaded bait stations Indoor

Mice No (not

tamper resistant) MICE: Place a single

unit at each placement location at 8 to 12 foot intervals SL/G No Use indoors only in areas inaccessible to children and pets.

RAMIK GREEN MINI BAIT PACKS EPA Registration Number: 6128 2

- 23 Bait packs

each with 1.5 ounce of bait 4.2

– 37.5

lbs Mice and

Rats Indoors and Outdoors Yes RATS : Place 2 to 8 bait

packs per placement at intervals of 15 to 30 feet. MICE : Open package and apply 1⁄4 to 1⁄2 ounces (1

- 2 level tablespoons) of bait at each placement at 8

- to 12

- foot intervals. Larger placements (up to 2 ounces) may be needed at points of very high house mouse activity. 6.25E

- 06 lb ai/patch SL/G No This product may only be used inside and within 100 feet of buildings or inside of transport vehicles (ships, trains, or aircraft). Not be sold in packaging less than 4 lbs of bait. Burrow baiting is prohibited.

### Page 23 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

RAMIK OATS KILLS GROUND SQUIRRELS EPA Registration Number: 6128 2

- 24 0.005

% a.i. Grain bait 4

- 30 lbs California Ground squirrels Use 2 to 4 pounds of bait

per station or 2.0E

- 04 lb ai/station SL/G

. Yes This anticoagulant bait may only be

used to control California ground squirrels in secured bait

- station applications in or near levee or ditch banks, around farm buildings, along fence lines, in orchards, in or near crops, and in non

- crop areas. Do not broadcast this bait, or apply it directly to food or feed crops. RAMIK MINI BARS ALL

WEATHER RAT AND MOUSE KILLER EPA Registration Number: 6128 2

- 26 Bait block

4

- 60 lbs

Rat and Mouse Yes Rats: Apply 4 to 16 one

ounce Ramik Mini Bars per placement at 15 to 30 feet Mice : Place one 1

- ounce Ramik Mini Bar at 8

- to 12

- foot intervals. SL/G No

This product may only be used inside and within 100 feet of buildings or inside of transport vehicles (ships, trains, or aircraft). Not to be sold in less than 4 lbs of bait. RAT AND MOUSE KILLER WITH DIPHACINO NE EPA Registration Number: 6128 2

- 41 0.005

% Pellets

Ready Mixed Yes Rats: Place 4 to 16 ounces of bait per placement. Space placements at intervals of 15 to 30 feet in infested areas. 5.26E

- 05 lb ai/bait station Mice: Apply 1⁄4 to 2 ounces (1

- 2 level tablespoons) of bait at each placement location at 8

- to 12

- foot intervals. SL/G No

DIPHACIN 110 CONCENTRA TE RODENTICID E EPA Registration Number: 6128 2

- 43 1 0.1 % Concentrate 1

- 50 lbs Yes SL/G

+ PF5 loade

rs Appl icato

rs SL/G No For commercial use only be used inside

and within 100 feet of buildings or inside of transport vehicles (ships, trains, or aircraft). Thoroughly mix one part of concentrate with 19 parts (by weight) of suitable bait material (e g cereal grains, oils, and sweeteners) For example, the formula in pellet form has been tested and found acceptable For commercial use only. May also be used

### Page 24 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

for burrow baiting. Do not broadcast bait.

DIPHACIN 110

- A CONCENTRA TE RODENTICID E EPA Registration Number: 6128 2

- 44 2.0 % Rodenticide only for formulation into registered products. Mixers must wear coveralls worn over short

- sleeved shirt and short pants, chemical

- resistant footwear, socks, a dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC

- 21C), protective eyewear, and waterproof gloves The following uses: in and around buildings, inside transport vehicles, in sewers (Norway rat, roof rat, and house mouse), orchards; rangeland (bait stations or spot baiting around burrow entrances); crop land (hand, underground application or around burrow entrances); forestry plan tations, and non

- crop

RAMIK BROWN EPA Registration Number: 6128 2

- 45 0.005% Pelleted 10

- 50 lbs Rats and Mice in Fruit Tree and Nut Orchards, Christmas Tree Farms, Tree plantation s, and Commerc ial nurseries for Voles No Inside burrows:

Rats: Place 4 to 16 oz. of bait per placement at 15

- to 30

- foot intervals. House Mice: Apply 1⁄4 to 2 oz. (1

- 2 level tablespoons) of bait at 8

- to 12

- foot intervals.

SL/G Yes For orchard aerial application only in those states specified in label. Apply after fall harvest and before new spring growth. Do not use hay cut after application and do not graze animals in treated areas. For ground applications use a commercially

- made seed or fertilizer spreader. Uniformly apply 20 lb of bait per acre for Orchard: Hand spot baiting; 1 1⁄2 oz. of product in each vole hole

or 4.7E

- 06 lb ai/patch

. Ground and Aerial Broadcasting: 20 lb product/A for Pine vole

or 1.0E

- 03 lb ai/acre and 10 lb product/acre for Meadow Vole or 5.0E

04 lb ai/acre RAMIK GREEN EPA Registration 0.005

% Pelleted. 4

- 60 lbs Rats and

mouse Yes Rats: 4 to 16 ounces of

bait per placement at 15 to 30 feet in infested SL/G No This product may only be used inside and within 100 feet of buildings or inside of transort vehicles (ships, trains, or aircraft). Not to be sold in packaging

### Page 25 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

Number: 6128 2

- 46 areas. 5.0E

- 05 lb ai/patch Mice : apply 1⁄4 to 2 ounces of bait at 8 to 12 foot intervals. 6 .25E

- 06 lb ai/patch that holds less than 4 pounds of bait. Burrow baiting prohibited.

PROMAR RAT & MOUSE KILLER EPA Registration Number: 6128 2

- 47 This product may only be used inside and within 50 feet of buildings or inside of transort vehicles (ships, trains, or aircraft). Not to be sold in packaging that holds less than 4 pounds of bait.

RAMIK GREEN BAIT PACKS EPA Registration Number: 6128 2

- 48 Bait pack of pelleted material Rats: Place 1 to 4 bait packs per placement at 15 to 30 feet interval. Mice: Open the one bait pack and apply 1⁄4 to 2 ounces (1

- 2 level tablespoons) of bait at 8

- to 12

- foot intervals. 6.25E

- 06 lb ai/patch This product may only be used inside and within 100 feet of buildings or inside of transort vehicles (ships, trains, or aircraft). Not to be sold in packaging that holds less than 4 pounds of bait. Burrow baiting prohibited.

RAMIK MOUSER RF KILLS MICE EPA Registration Number: 6128 2

- 57 0.005

% Cake Bait in Refillable Bait Station 2 to 16

ounce. Mini bar weighs 28.3 grams. Mice Yes Mice: Place one Mini Bar in the bait station.at 8 to 12 foot internals. SL/G No Use indoors only.

RAMIK GREEN AG EPA Registration Number: 6128 2

- 63 Pellet 4

- 60 lbs Rats and Mice Yes Rats: 4 to 16 ounces of

bait per placement at 15 to 30 feet. 5.0E

- 05 lb ai/patch Mice: apply 1⁄4 to 2 oz. of bait at 8 to 12 foot intervals 6.25E

- 06 lb ai/patch SL/G

. No This product may only be used inside

and within 100 feet of buildings or inside of transort vehicles (ships, trains, or aircraft). Not to be sold in packaging that holds les s than 4 pounds of bait. Burrow baiting prohibited.

### Page 26 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

SCIMETRI CS, LTD. CORP0RATI ON PO BOX 1045 WELLING TON CO 80 549 970/482

- 1330 KAPUT

FIELD RODENT BAIT B EPA Registration Number: 7250 0

- 11 0.0025

% Pelleted 5

- 50 lbs Ground squirrels and their fleas No Manually scatter 1⁄2 cup

per burrow in an area no larger than 50 ft 2 or 8 feet in diameter. 6.25E

- 06 lb ai/burrow

SL/G Yes Used to control California ground squirrels in parks, golf courses, fruit tree orchards (dormant season only),

non

- crop rights

- of

- way and non

- crop areas and aid in the reduction of fleas ground squirrels.

KAPUT

- D BURROW BUILDER POCKET GOPHER BAIT EPA Registration Number: 7250 0

- 12 0.005

% Pellet 25

- 50 lbs Pocket Gopher No (only

below ground applicati ons) Mechanical applicator:

6

- 8 lb of bait per acre 4.0E

- 04 lb ai/acer For control only of [Kills only] Pocket Gophers ( Geomys sp. and Thomomys sp.) in and bordering crops (alfalfa, forage, hay, vegetables and grains); rangeland; orchards; and

non

- crop areas (forestry plantations, golf courses and other turf areas, levee/ditch banks, nurseries, parks and around agricultural buildings). KAPUT

- D COMBO BAI T BLOCKS EPA Registration Number: 7250 0

- 18 0.005% Bait Blocks 4

- 50 lbs Norway Rats, Roof Rats, House Mice and Fleas Yes Rats: Apply 3 to 15

blocks per bait placement at 15 to 30 feet House Mice: 1 bait block per placement at 8 to 12 feet in infested

area.

SL/G No This product may be used only inside and within 50 feet of buildings or inside transport vehicles (ships, trains or aircraft).

KAPUT D PRAIRIE DOG BAIT EPA Registration Number: 7250 0

- 22 0.005% Grain Bait 5 to 2000 lbs Prairie

Dogs on rangeland and adjacent

non

- crop

areas No (only undergro und applicati ons) Application by Hand and

mechanical bait placement : Apply 1⁄4 cup of bait (approx. 2 ounces or 56 grams) at least 6 inches down prairie dog burrows. 6.25E

- 06 lb ai/station Yes This pro duct may only be used in underground applications. Do not apply bait at or above ground level. Treat only active burrows. Apply between October 1 and March 15 of the following year, when animals will most readily take the grain bait. Do not allow livestock to graze in treated areas for 14 days after treatment and when no bait is found above ground. DIPHACINO NE TECHNICAL 98.8% Concentrate 5 to 200 lbs Only for formulation into a rodenticide for use in and around buildings, inside transport vehicles, in sewers (Norway rat, roof rat and house mouse); in pome fruits, stone fruit, nurseries, forestry plantations, rangeland and selected non

- crop sites.

### Page 27 of 32

Table A.3. Preliminary Use Profile Table for Diphacinone (PC 067701) and Sodium Salt (PC 067705)

Company Formulation

[EPA Reg. No.] Percent

ai Formulation

Type Net

Contents Packaging Target

and Area Tamper

Resistant Bait Stations Application Rate PPE RUP Use Directions and Limitations

EPA Registration Number: 7250 0

- 23
KAPUT GROUND SQUIRREL BAIT EPA Registration Number: 7250 0

- 24 0.0025

%

Grain Bait 4

- 50 lbs California Ground Squirrel Yes 2

- 4 lbs of bait per

station at 20 to 100 feet apart. 1.0E

- 04 lb ai/station

SL/G No This product may be used only inside and within 100 feet of buildings or inside transport vehicles (ships, tra ins or aircraft). Do not broadcast. Do not sell this product in individual containers holding less than 4 lbs

.

KAPUT

- D POCKET GOPHER BAIT EPA Registration Number: 7250 0

- 9 0.005

% 1

- 50 lbs Pocket gophers No (only

below ground applicati ons) 1/2 cup of Kaput bait

into the burrow. If using the Sub

- Station place 1 lb. of product 5.0E

- 05 lb ai/burrow For use in and bordering crops (alfalfa, forage, hay, vegetable and grains0 rangeland, orchards, and non

- crop areas ( forestry plantations, golf courses, lawns, parks) . Make 2

- 3 manual applications per burrow system. Using a long

- handled teaspoon, remove the plug from the mound

### Page 28 of 32

Attachment 4. En dpoint Selection Table

Table A.4: Summary of Toxicological Doses & Endpoints for Diphacinone Occupational Human Health Risk Assessment

Exposure Scenario Point of Departure (PO D) Uncertainty /

FQPA Safety Factors Level of Concern

for Risk Assessment Study and Toxicological Effects

Dermal Short Term (1

- 30 days)and Intermediate Term (1

- 6 months) Maternal

NOAEL = 0.10 mg/kg/day UF A = 10x

UF H = 10x Occupational LOC

for MOE = 100 21

- day Dermal Study in Rabbits

Maternal LOAEL = 50 mg/kg/day Based on clinical signs consistent with anti

- coagulant effects at the LOAEL of 1 mg/kg/da

. Inhalation Short Term (1

- 30 days)and Intermediate Term (1

- 6 months) NOAEL =

0.085 mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1X Occupational LOC

for MOE = 100 14

- day Oral Study in SD rats

LOAEL = 0.175 mg/kg/day Based on decreased prothrombin and activated partial thromboplastin times following repeated exposure. N o route

specific study was available. Cancer (dermal and inhalation) N/A

Point of Departure (P O D) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

### Page 29 of 32

Attachment 5. Toxic ology Data Requirements

The requirements (40 CFR 158.500) for non

- food uses are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.5: Toxicology Data Requirements for Diphacinone
Guideline Study Type Required Submitted Satisfied 870.1100 Acute Oral Toxicity Yes Yes Yes
870.1200 Acute Dermal Toxicity Yes Yes Yes
870.1300 Acute Inhalation Toxicity Yes Yes Yes
870.2400 Acute Eye Irritation Yes Yes Yes
870.2500 Acute Dermal Irritation Yes Yes Yes
870.2600 Skin Sensitization Yes Yes Yes
870.3100 90

- Day Oral Toxicity in Rodents Yes Yes Yes
870.3150 90

- Day Oral Toxicity in Non

- Rodents CR No NA
870.3200 21/28

- Day Dermal Toxicity NR No NA
870.3250 90

- Day Dermal Toxicity Yes Yes Yes
870.3465 90

- Day Inhalation Toxicity CR No Yes b

870.3700 Prenatal Developmental Toxicity Study (Rat) Yes Yes Yes

Prenatal Developmental Toxicity Study (Rabbit) Yes No Yes b

870.3800 Reproduction and Fertility Effects Yes No Yes b

870.4100 Chronic Toxicity (Rodent) CR No NA

870.4200 Carcinogenicity (Rat) CR No NA

Carcinogenicity (Mouse) CR No NA 870.5100 Bacterial Reverse Mutation Test Yes Yes Yes
870.5300 870.5375 i n vitro Mammalian Cell Gene Mutation Test

i n vitro Mammalian Chromosome Aberration Test Yes a Yes Yes Yes

870.5385 870.5395 Mammalian Bone Marrow Chromosomal Aberration Test

Mammalian Erythrocyte Micronucleus Test Yes a No Yes Yes

870.6100 Delayed Neurotoxicity of Organophosphorus Substances (Acute, Hen) CR No NA

Delayed Neurotoxicity of Organophosphorus Substances (28

- Day, Hen) CR No NA

870.6200 Neurotoxicity Screening Battery (Acute, Rat) Yes No Yes b

Neurotoxicity Screening Battery (90

- Day, Rat) Yes No Yes b

870.6300 Developmental Neurotoxicity Study CR No NA
870.7200 Companion Animal Safety CR No NA
870.7485 Metabolism and Pharmacokinetics Yes Yes Yes
870.7600 Dermal Penetration CR No NA
870.7800 Immunotoxicity Yes No Yes b CR = Conditionally Required. NA = Not Applicable.

a Either guideline study type may be used to satisfy the data requirement (e.g

. 870.5300 or 870.5375)

. b Study not required ( U. Habiba TXR 0057326

, 12/1 5 /2015 ).

### Page 30 of 32

Attachment 6

. Toxicity Profile for Diphacinone

Table A.6.1: Acute Toxicity of Diphacinone Technical

Guideline No. Study Type MRID No. Species Results Toxicity Category

870.1100 Acute Oral

Toxicity 00060605 Rat LD 50 (M) = 2.5 (1.32

- 3.44) mg/kg LD 50 (F) = 2.1 (1.55

- 2.86) mg/kg combined = 2.3 (1.86

- 2.88) mg/kg I

870.1100 Oral 42245202 Rat LD 50 (M) = 6.8 mg/kg LD 50 (F) = 8.0 mg/kg combined = 7.0 (5.2

- 9.5) mg/kg I

870.1200 Acute Dermal

Toxicity 42507001 Rabbit LD 50 (M) = 3.6 (0.6

- 20.8) mg/kg LD 50 (F) = not done I

870.1300 Acute

Inhalation Toxicity 43000401 Rat LC 50 (M) < 0.6 μg/L LC 50 (F) < 0.6 μg/L I

870.2400 Acute Eye

Irritation 42245203 Rabbit Moderate irritation clearing by day 4 III

870.2500 Acute Dermal

Irritation Unknown Rabbit Slight erythema clearing within 48 hours, but 4/6 rabbits died between days 8 and 10. IV

870.2600 Dermal

Sensitization 42132501 Guinea Pig Neither a dermal irritant nor a sensitizer at a

non

- lethal dose level (2.5 mg/day) N/A

### Page 31 of 32

Table A.6.2: Toxicity Profile of Diphacinone Technical
Guideline Study Type MRID (year) / Doses / Classification Results

870.3100 14

- Day Oral

Toxicity in Rodents (Rat) 43260701

Single Dose 0.13, 0.20, 1.00 and 2.50 mg/kg/day

Repeat Dose 0.025, 0.040, 0.085, and 0.175

Acceptable/non

- guideline Single Dose NOAEL = 0.13 mg/kg/day LOAEL = 0.20 mg/kg/day based on increased PT and APTT.

Repeat Dose NOAEL = 0.085 mg/kg/day LOAEL = 0.175 mg/kg/day based on increased PT and APTT.

870.31 00 21

- Day Oral

Toxicity in Rodents (Mouse) 00077319

0.1, 0.5, 1.0, 2.5, 5, 10 and 20 mg/kg/day

Unacceptable/non

- guideline NOAEL = 0.5 mg/kg/day LOAEL = 1 mg/kg/day based on hemorrhages & external bleeding

Clotting factors were not evaluated.

870.3200 21/28

- Day

Dermal Toxicity (Rabbit ) 00074637

0, 0.1, 10 mg/kg/day

Acceptable/non

- guideline NOAEL = 0.1 mg/kg/day LOAEL = 1 mg/kg/day based on hemorrhagic lesions in tissues/organs.

Clotting factors were not evaluated.

870.3465 90

- Day

Inhalation Toxicity Not required by HASPOC

870.3700 Prenatal

Developmental Toxicity Study (Rat) 42834801

0, 0.010, 0.025, 0.075 mg/kg/day NOEL = 0.025 LOEL = 0.075 mg/kg/day

Based on clinical signs consistent with anti

coagulant activity (reddish urogenital staining and reddish fluid in cage). Clotting factors were not evaluated. No effects were reported on body weights, food consumption or histopathology.

Developmental NOE L = 0.075 mg/kg/day Prenatal Developmental Toxicity Study (Rabbit) Not required by HASPOC

870.3800 Reproduction and

Fertility Effects (Rat) Not required by HASPOC

870.5100 Bacterial

Reverse Mutation Test ( Salmonella typhimurium ) 42350901

TA98, 100, 1535, 1537 & 1538 5

- 500 μg/plate with and without S9 Negative

870.5300 in vitro

Mammalian Cell Gene Mutation Test 42359901

CHO AS52 0.167 to 125 μg/ml Negative

### Page 32 of 32

Table A.6.2: Toxicity Profile of Diphacinone Technical
Guideline Study Type MRID (year) / Doses / Classification Results

870.5395 Mammalian

Erythrocyte Micronucleus Test (Mouse) 42406801 Negative

870.6200 Acute

Neurotoxicity Screening Battery (Rat) Not Required by HASPOC 90

- Day Neurotoxicity Screening Battery (Rat)

870.7485 Metabolism and

Pharmacokinetic s (Rat) 92049009

SD Rats

- 0.18, 0.4, 0.5, 1 mg/kg Norwegian Rats

– 3.5 mg/kg Swiss Albino Mice

– 0.6 mg/kg Absorption appeared reaching peak concentration at 4 hours after administration. Distribution data showed that the liver, muscle, blood, fat, and lung were the tissues demonstrating the greatest retention of the test chemical in the order liver (14 2 5% of the dose), muscle (0.18 4.4% of the dose), fat (0.55 1.16% of the dose), and lung (0.04 0.5% of the dose). A half

- life of 17 hours was estimated. Elimination of diphacinone derived radioactivity was prim arily in feces, with between 47

- 77% of th e dos e in feces of rats, and 69

- 73% of the dose in mice. At least five metabolites of diphacinone were identified in urine, feces, and/or liver. These metabolites represent hydroxylated products of diphacinone occurring on the phenyl and indandionyl rings.

870.7800 Immunotoxicity

(Rat) Waived by HASPOC