OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460



### March 3 , 201 6

PC Code: 112001 DP Barcode: 429381

MEMORANDUM

SUBJECT: Bromadiolone : Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of Registration Review

FROM: Michael Lowit, Ph.D., Ecologist Stephen We nte, Ph.D., Biologist Sujatha Sankula , Ph.D., Branch Chief Environmental Risk Branch I Environmental Fate and Effects Division (7507P)

TO: Ricardo Jones , Chemical Review Manager Tom Moriarty , Team Leader Neil Anderson , Branch Chief Risk Management and Implementation Branch I Pesticide Re

- evaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the environmental fate, ecological risk, endangered species, a nd drinking water exposure assessments to be conducted as part of the Registration Review of the rodenticide bromadiolone (CAS # 28772

- 56

- 7 ). Functioning as the first stage of the risk assessment process for registration review, this problem formulation provides an overview of what is currently known about the environmental fate and ecological effects associated with bromadiolone and its deg radates. It also describes the preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing risk to non

- target species in support of the registration review of bromadiolone . This document also recommends studies that should be included in a generic data call

- in (DCI) to address uncertainties surrounding the environmental fate and potential ecological effects of bromadiolone

.

### 2 EFED anticipates that the ecological risk assessme nt (ERA) will focus primarily on risk to terrestrial organisms and that neither an aquatic nor d rinking water assessment (DWA) will b e conducted because potential exposure is expected to be minimal.

EFED recommends the following studies to reduce uncertai nty in the risk assessment 

### :

• 850.2100: Avian oral toxicity (passerine species) (bromadiolone; TGAI) 1



### • 850.2300: Avian reproduction (upland game species) (bromadiolone; TGAI)

• 850.2300: Avian reproduction (waterfowl species) (bromadiolone; TGAI)

In addition, non

- guideline data on toxicity to terrestrial invertebrates other than the honeybee may be useful for reducing uncertainty in the risk assessment.

Toxicity data from other sources ( e.g., other anti coagulants ) may be used in the absence of data f

or bromadiolone . Use of surrogate data may over or underestimate risk of bromadiolone use.

EFED recommends the following label changes to reduce uncertainty in the risk assessment :



### As l abeled

, s ewer use requires securing bait in some manner to minimize chances of removal by
rats or water

. However, labels also state that on e method is to place bait on a board supported by opposing steps of the ladder. If the board is above the high water mark then this would reasonably reduce the likelihood of removal b y water; however, if the bait is not physically attached in some manner to the board then it is possible that it could be easily knocked off by
rats or other animals

. EFED recommends revising the label to specify that bait must be physically secured to the board.

Other considerations :



### Labels do not require use of a bait station in sewers. Although the product is placed below ground and contained inside of a sewer (not in contact with the water) , there is potential direct
exposure to non

- target anima ls

. Non

- target terrestrial a nimals may be exposed through direct
exposure to bait if they are able to gain access into the sewer. Furthermore, direct exposure may occur if the bait becomes unsecured (e.g., chunks of bait blocks could be knocked or broken off as bait is eaten ) , flushed out of the sewer system, and then made more widely available to non

target animals

. If the product become s unsecured then i t is assumed that the bromadiolone is more likely to flush out of the sewer rather than substantially dissolve in water

, in part because it is typically embedded in some sort of waxy material

. These direct exposure pathway s from

sewer use ( i.e., a non

- target animal directly consum ing bait inside or outside of the sewer ) would not be consider ed complete ( except for non

- target animals that can gain access to the bait in the station) if bait is not only secured within the sewer but also contained in a bait station. In the absence of bait stations it will be assumed that a greater number and var iety of animals may directly consume bromadiolone placed in sewers.

1 The observation period should be extended beyond that of a standard 850.2100 study (14 days) given that effects from bromadiolone poisoning are not immediate (i.e., it should be long enough to capture effects of bromadiolone poisoning and continue until e vidence of toxicity has subsided).

### 3 

# P roblem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of the Registration Review of Bromadiolone

CAS: 28772

- 56

- 7 PC Code: 112001

Environmental Fate and Effects Division Prepared by: Michael Lowit, Ph.D., Ecologist 

### Stephen Wente, Ph.D., Biologist U.S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch I 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 Reviewed by: Brian Anderson, Branch Chief , ERB2 

### O O OH OH

Br

### 4 Table of Contents

1. Purpose

................................ ................................ ................................ ................................ ........ 5 2. Problem Formulation

................................ ................................ ................................ .................. 5 2.1. Nature of Regulatory Action

................................ ................................ ................................ 5 2.2. Previous Assessments

................................ ................................ ................................ .......... 5 2.2.1. Ecological Risk Assessments

................................ ................................ ........................ 5 2.2.2. Drinking Water Exposure Assessments

................................ ................................ ........ 5 2.2.3. Other Actions

................................ ................................ ................................ ................ 5 3. Stressor Source and Distribution

................................ ................................ ................................ 6 3.1. Mechanism of Action

................................ ................................ ................................ .......... 6 3.2. Overview of Pesticide Use and Usage

................................ ................................ ................ 6 3.3. Physical, Chemical, and Environmental Fate Properties of Bromadiolone and its Degradates

................................ ................................ ................................ ................................ ... 7 3.4. Monitoring Data

................................ ................................ ................................ .................. 8 3.5. Clean Water Act

................................ ................................ ................................ .................. 8 4. Receptors

................................ ................................ ................................ ................................ .... 9 4.1. Toxicity of Bromadiolone

................................ ................................ ................................ ... 9 4.2. Secondary Toxicity to Birds and Mammals

................................ ................................ ...... 11 4.3. Incident Databases Review

................................ ................................ ............................... 12 5. Exposure Pathways of Concern

................................ ................................ ............................... 13 6. Analysis Plan

................................ ................................ ................................ ........................... 13 6.1. Stressors of Concern

................................ ................................ ................................ .......... 14 6. 2. Measures of Exposure

................................ ................................ ................................ ........ 14 6.3. Measures of Effect

................................ ................................ ................................ ............. 15 6.4. Integration of Exposure and Effects

................................ ................................ .................. 15 6.5. Endangered Species Assessments

................................ ................................ ...................... 16 6.6. Endocrine Disruptor Screening

................................ ................................ .......................... 17 6.7. Drinking Water Assessment

................................ ................................ .............................. 17 6.8. Preliminary Identification of Data Gaps

................................ ................................ ............ 17 6.8.1. Environmental Fate Data

................................ ................................ ............................ 17 6.8.2. Ecological Effects Data

................................ ................................ ............................... 18 7. References

................................ ................................ ................................ ................................ 22 APPENDIX A. Names and Structures of Bromadiolone and its Major and Minor Degradates

. 23 APPENDIX B. STIR v.1.0 Inputs and Outputs

................................ ................................ ........... 25

### 5 1. Purpose The purpose of this problem formulation is to provide an understanding of what is known about the environmental fate, ecological effects, and currently registered uses of bromadiolone , a second

- generation anti coagulant rodenticide

. This document provides a plan for analyzing data relevant to bromadiolone and for conducting environmental fate, ecological risk, endangered species, and drinking water exposure assessments for its registered uses. A dditionally, this problem formulation identifies data gaps, uncertainties, and potential assumptions used to address those uncertainties relative to characterizing the potential ecological risk associated with the registered uses of bromadiolone

.

2. Proble m Formulation

2.1. Nature of Regulatory Action As part of the implementation of the Registration Review program 2 

### pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Agency is beginning its evaluation of bromadio lone to determine whether it continues to meet the FIFRA standard for registration. This problem formulation in support of the R egistration R eview of bromadiolone will be posted in the initial docket which will be open to the public phase of the review pr ocess.

2.2. Previous Assessments

2.2.1. Ecological Risk Assessments

Bromadiolone was first registered in the US in 19 80 as a rodenticide only for indoor use ; it is currently registered for indoor use s as well as outdoor uses (above or underground around buildings and in sewers). Previous ERAs identified risk concerns for mammals and birds through both primary ( direct consumption of bait) and secondary (consumption of prey that have ingested bromadiolone ) poisoning ( see most recent assessment for a comprehensive account of past assessments: USEPA, 201 1 )

. 2.2.2. Drinking Water Exposure Assessments

A DWA has not been conducted

. EFED anticipates that a DWA will not be performed for the Registrat ion Review of bromadiolone because exposure through drinking water is expected to be minimal.

2.2. 3

. Other Actions Risk mitigation measures were imposed as part of r eregistration e ligibility of bromadiolone and nine other rodenticides (USEPA, 2008). Requi rements imposed to mitigate ecological risk included (1) minimum package size requirements, (2) sales and distribution restrictions, (3) use site restrictions, and (4) the require d use of bait stations for all outdoor, above

- ground uses.

In 2011, EPA presented to the Science Advisory Panel (SAP) an extensive assessment of the potential for primary and secondary exposure to several anti coagulant rodenticides, which were

2 http://www2.epa.gov/pesticide

- reevaluation/registration

- review

- process

### 6 subject to a Notice of Intent to Cancel (NOIC). 3 

### Although bromadiolone was not one of the rodenticides subject to that NOIC , the assessment approach is broadly applicable to bromadiolone and other anti coagulant rodenticides

.

3. Stressor Source and Distribution

3.1. Mechanism of Action

Bromadiolone is a second

- generation anticoagulant rodenticide that acts by reducing the action of vitamin

- K; thereby, disrupt ing normal blood

- clotting mechanisms and induc ing capillary damage (Pelfrene, 1991). Death results from hemorrhage

, and exposed animals may exhibit increasing weaknes s prior to death. Bromadiolone may provide a lethal dose after a single feeding; however, death is usually delayed for a period of days because the animal may have vitamin

- K reserves. Behavior also may be affected (Cox and Smith, 1992). In general, seco nd

generation anticoagulants tend to be more acutely toxic and remain longer in body tissues of primary consumers than first

- generation anticoagulants (e.g., warfarin, diphacinone, and chlorophacinone)

.

3.2. Overview of Pesticide Use and Usage Bromadiolone uses and application rates are reported in the most recent Label Use Information System (LUIS) report provided by the Biological and Economic Analysis Division (BEAD) (USEPA, 2015). Bromadiolone is labeled for indoor and outdoor use in and ar ound man

- made
structures su ch as buildings and vehicles. Outdoor baiting must be within 50

- 100 ft of the structure. Furthermore, bait stations are mandatory for all outdoor, above ground uses. Two other outdoor uses are permitted and neither one require s use of a bait station : within sewers and animal burrows. In burrows, bait must be placed at least 6 inches deep according to some but not all labels and no labels require that the burrow be covered or capped . In sewers, the bait is securely attached to a structure although placement on a board supported by opposing steps of the ladder is also permitted (presumably unsecured). The maximum application rate is 0.00005 lb ai/manhole for sewer uses and 0.00005 lb ai/ placement for all other uses. 4



### Bromadiolone products are used to control commensal rodents; that is, house mouse ( Mus musculus ), Norway rat ( Rattus norvegicus ), and roof rat ( Rattus rattus )

. Some products can also be used to control for certain non

- commensal rodents: cotton rat ( Sigmo don hispidus ), eastern harvest mouse ( Reithrodontomys humuli s ), golden mouse ( Ochrotomys nuttalli ), Polynesian rat ( Rattus exulans ), meadow vole ( Microtus pennsylvanicus ), white

- throated woodrat ( Neotoma albigula ), southern plains woodrat ( Neotoma micropus ), and Mexican woodrat ( Neotoma mexicana ).

The registration review risk assessment will be based on current label information at the time of assessment as provided by BEAD.

3 http://www.regulations.gov/#!docketBrowser;rpp=50;po=0;D=EPA

- HQ

- OPP

- 2011

- 0718

4 Rates reflect some recent label updates that were not captured in the most recent LUIS report.

### 7 3.3. Physical, Chemical, and Environmental Fate Properties of Bromadiolone and its De gradates

Bromadiolone ( 3

- [3

- (4'

- bromo[1,1'

- biphenyl]

- 4

- yl)

- 3

- hydroxy

- 1

- phenylpropyl]

- 4

- hydroxy

- 2H

1

- benzopyran

- 2

- one ) is a diastereomeric mixture

. It has limited solubility in water (1.21 ppm) and is unlikely to volatilize. Select physical and chemical properties are presented in Table 1

.

Table 1

. Physical and Chemical Properties of Bromadiolone
Property Value Source

Common Name Bromadiolone

CAS Registry No. 28772

- 56

- 7 PPDB 1

PC Code 112001 PPDB 1

Structure MRID 43594301

Chemical Name (CAS) 3

- [3

- (4'

- bromo[1,1'

- biphenyl]

- 4

- yl)

- 3

- hydroxy

- 1

- phenylpropyl]

- 4

- hydroxy

- 2H

- 1

- benzopyran

- 2

- one PPDB 1

SMILES notation c1cc(Br)ccc1c(cc2)ccc2C(O)CC(c3ccccc3) C4=C(O)c5ccccc5OC4(=O) PPDB 1

Molecular Formula C 30 H 23 BrO 4 PPDB 1

Molecular Weight 527.40 g/mol PPDB 1

Physical State Solid; f in e w hite to off

- white powder MRID 46933604

Vapor pressure < 10

- 7 torr at 25 ° C MRID 46933604

Henry’s Law constant 5.48 × 10

- 10 atm m 3 /mol @ 20°C MRID 46933604

Specific Gravity/ Density 0.680 g/ml MRID 46933604

Solubility in water 1.21 ppm @ pH 7 and 25 ° C MRID 46933604

log K ow 7.0 MRID 46933604

1 PPDB = Pesticide properties database; http://sitem.herts.ac.uk/aeru/ppdb/en/index.htm



### Bromadiolone has a half

- life of 128 days in soil (MRID 43594301 ) and can generally be considered immobile (MRID 43000702, 42237501, 00161972, 00161973, and 00161988) except in soils of low organic matter and clay, such as sand. Bioaccumulation concentration factors (BCFs) were l60 X for edible tissues

, 1658 X for non

- edible tissues, and 460 X for whole fish. Sixteen percent to 35.8% of b romadiolone residues were retained in fish t issues after depuration. Table 2 summarizes the environmental fate data for bromadiolone. Chemical n ame s , structure s , and formatio n of major and minor degradates are reported in Appendix A

. O O OH OH

Br

### 8 Table 2 . Summary of the Environmental Fate Properties of Bromadiolone Property Value Source Hydrolysis half

- life (days) pH = 5 pH = 7 pH = 9 3 84 Stable Stable MRID 42237501

Aerobic soil metabolism half

- life (days) 128 MRID 43594301 Soil adsorption coefficient K d (ads) K d (ads) BBA2.1 = 93.2 K d (ads) Bruckenberg = 95.7 K d (ads) Dossenheim = 37.2 MRID 45692901

Laboratory accumulation in bluegill sunfish bioaccumulation factor ( Lepomis macrochirus )

Depuration (%TTR remaining at 14 days) Edible = 160.7 N on

- edible = 1658.4 Whole fish = 459.9

Edible = 35.8% N on

- edible = 16.0% Whole fish = 27% MRID 00161965



### Major degradates

There are two major degradates identified in the aerobic soil metabolism study (MRID 43594301 ). These degradates are m etabolite 1 (1,3

- diphen y l

- 5(4 ’

- bromo

- bi phenyl pentane

- 1

- ol) and m etabolite 3 (1,3

- diphen y l

- 5(4 ’

- bromo

- bi phenyl pentane

- 1,5

- diol). Their st ructures can be found in Appendix A

. EFED is not aware of any fate or toxicity data for these compounds.

3.4. Monitoring Data A search of the water quality databases accessible through the Water Quality Portal 5 

### identified only 14 samples for bromadiolone. All of the samples were collected by the National Park Service Water Resources Division from lakes and streams in the Rocky Mountains area of Colorado, Montana, and Wyoming. None of the 14 samples exceeded the detection limit of 50 ng/L. Available data from sources including federal and state agencies will be considered in the ERA.

Residues have been detected in wildlife

. S amples from those organisms were collected for research surveys and follow

- up to ecolo gical incidents associated with pesticide use ( see Section 4.3 )

.

3.5. Clean Water Act Bromadiolone is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 6 

### In addition, no Total Maximum Da ily Loads

5 http://waterqualitydata.us/portal

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_ group_id=885

### 9 (TMDL) have been developed. 7 

### The Impaired Waters and TMDL website can be consulted for more information. 8 

### Aquatic benchmarks have not been established for bromadiolone. 9



### 4. Receptors Consistent with the process described in the Overview Document (USEPA, 2004), the risk assessment for bromadiolone relies on a surrogate species approach. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate the potential effects on a variety of species (receptors) included under these taxonomic groupings.

A cute and chronic toxicity data from studies submitted by pesticide registrants along with the available o pen literature will be used to evaluate the potential direct and indirect effects of bromadiolone to aquatic and terrestrial receptors. This includes toxicity on the technical grade active ingredient, degradates, and when available, formulated products ( e .g. , “Six

- Pack” studies). Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 10 

### , which employs a literature search engine for lo cating chemical toxicity data.

A summary of bromadiolone toxicity data is provided in Tabl e 3 and 4 of Section 4.1

. Secondary toxicity data are presented in Section 4.2 (Table 5)

. A review of ecological incidents associated with bromadiolone is provided in Section 4. 3

. The ECOTOX database will be searched when the risk assessment for bromadiolone is prepared. At that time, EFED will review the endpoints from open literature studies that are more sensitive than those from available guideline studies.

4.1. Toxicity of Bromadiolon e
Table 3

. Summary of Aquatic Taxa Toxicity Endpoints for Broma diolone Type of Study Species Toxicity Value MRID Acute

– Freshwater Fish Rainbow trout ( Salmo gairdneri ) 96

- hr LC 50 = 1.4 mg/L (1.1

- 1.7) 1 (nom)

NOAEC ≤ 0.46 mg/L LOAEC < 0.46 mg/L based on loss of equilibrium

Other sublethal effects: lethargy, dark coloration, and erratic swimming with gyrations 00070140

Bluegill Sunfish ( Lepomis macrochirus ) 96

- hr LC 50 = 3.0 mg/L (2.4

- 3.7) 1 (nom)

NOAEC = 1.3 mg/L LOAEC = 2.2 mg/L based on mortality

Other sublethal effects: surfacing and dark coloration 00070141

7 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

8 http://www.epa.gov/tmdl

9 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/aquatic

- life

- benchmarks

- pesticide

registration/

10 http://cfpub.epa .gov/ecotox/

### 10 Type of Study Species Toxicity Value MRID

Acute

– Freshwater Invertebrate Water flea ( Daphnia magna ) 48

- hr EC 50 = 0.24 mg/L (0.18

- 0.30) 1 (nom)

NOAEC = 0.088 mg/L LOAEC = 0.19 mg/L based on mortality 00070685

48

- hr EC 50 = 2 mg ai/L (1.8

- 2.6 ) 1

NOAEC = 1.2 mg ai/L LOAEC = 1.8 mg ai/L based on mortality 42093302

1 Range is 95% confidence interval. Nom = nominal concentration



### Table 4

. Summary of Terrestrial Taxa Toxicity Endpoints for Bromadiolone Type of Study Species Toxicity Value MRID

Acute

– Avian Oral Dose Bobwhite quail ( Colinus virginianus ) LD 50 = 170 mg ai /kg

- bw (115

- 261) 1

NOAEL = 5 0 mg ai/kg

- bw LOAEL = 100 mg ai/kg

- bw based on mortality

The observation period was 30 days. 00143279 2

Acute

– Avian Dietary Bobwhite quail ( Colinus virginianus ) LC 50 = 37.6 mg ai /kg

- diet ( 8.9

- 84.5 ) 1 Slope = 0.83 (0.42

- 1.23) 1

NOAEC < 10 mg ai /kg

- diet LOAEC ≤ 10 mg ai /kg

- diet based on mortality

The o bservation period was 25 days after the exposure period

. 00143280 3

Mallard duck ( Anas platyrhynchos ) LC 50 = 158 mg ai /kg

- diet (7

- 762) 1 Slope = 0.46 (0.11

- 0.81) 1
NOAEC < 19 mg ai/kg

- diet LOAEC ≤ 19 mg ai/kg

- diet based on mortality, clinical signs of toxicity (reduced water consumption, lethargy, and mild anorexia) with recovery by day 15, and reduced food consumption with recovery by day 10.

Other s ublethal effects: bloody droppings, loss of coordination, and blood filled cysts on bill).

The o bservation period was 25 days after the exposure period. 00143278 3

Acute

– Mammalian Oral Dose Laboratory R at ( Wistar albino ) LD 50 = 0.6 mg ai/kg

- bw

Sublethal effects were not reported.

The observation period was 14 days. 00241703 4

Developmental

– Mammalian 10

- day Oral Dose Laboratory rat ( Sprague

- Dawley ) NOAE L = 0.035 mg ai/kg

- bw LOAE L = 0.070 mg ai/kg

- bw based on vaginal bleeding, hy potonicity, pale eyes, and mortality 92196014 5

1 Range is 95% confidence interval.

### 11 2 A TEP (Rat

- A

- Rest) study with bobwhite quail resulted in inconclusive toxicity (LD 50 > 1% product of body weight or approximately 0.08675 mg ai/kg

- bw) (MRID 00145323) . Dose levels were presented in terms of Rat

- A

Rest as a percentage of body weight; thus, the dose level in terms of mg ai/kg bw is based on the average weight of all birds at the highest test concentration.

3 Additional TGAI studies with bobwhite quail and mallard duck with a shorter recovery period (14 days) resulted in less sensitive endpoints (Accession # 249995). Another TGAI study (MRID 44000202, un

- reviewed) is available for mallard duck; however, a cursory review of the data indicates that the o bserved pattern of mortality is not suitable for calculation of a LC 50 value. TEP (Rat

- A

- Rest) studies with bobwhite quail (MRID 00145321) and mallard duck (MRID 00145322) resulted in inconclusive toxicity (LC 50 > 10 mg ai/kg

- diet and LC 50 > 20 mg ai/kg

b w; respectively).

4 Test material was 1% bromadiolone and 99% corn starch instead of TGAI. Studies with bromadiolone concentrate (MRID 41900001) and TGAI (MRID 46993003) did not provide definitive endpoints: LD 50 = 0.56

- 0.84 mg ai/kg

bw and LD 50 < 5 mg/kg

- bw, respectively.

5 A chronic (2

- generation reproduction) study is unavailable.



### 4.2. Secondary Toxicity to Birds and Mammals

Available data for secondary toxicity (consumption of prey that have ingested bromadiolone) to birds and mammals are presented in Table 5

.

Table 5

. Summary of Secondary Exposure Hazards of Bromadiolone to Birds and Mammals (Laboratory Studies)

Predator/ Scavenger

Species Prey Offered Number of Prey Offered Daily per Predator/ Scavenger Number of Predators
per Exposure

Duration Number of Dead Predators/ Scavengers Signs of Toxicity in Survivors MRID

Barn owl ( Tyto alba ) Rats fed choice of 0.005% bait or untreated bait for 5 days. 1

- 2 1 for 1 day 2 for 3 days 1 for 6 days 2 for 10 days
All observed for 20 days. 0 0 0 1 None

46750931 40072202

Barn owl ( Tyto alba ) Mice were fed commercial bait (% ai
was not reported) and allowed to die. 2

- 3 6 for 1 day 6 for 3 days 6 for 6 days 0 0 0 Increased blood coagulation time, returning to normal after 10 days. 48590804

Stone marten ( Martes foina ) Yellow

necked field mice fed 0.005% bait in excess to feed for 4 days

. 4

- 8 2 for 1 day 2 for 4 days
All observed for 3 weeks. 0 0 Increased frag ility of small blood vessels of the muscles on top of the skull for individuals exposed for 4 days

. 48590802

### 12 Predator/ Scavenger

Species Prey Offered Number of Prey Offered Daily per Predator/ Scavenger Number of Predators
per Exposure

Duration Number of Dead Predators/ Scavengers Signs of Toxicity in Survivors MRID

Mongoose ( Herpestes auropunctatus ) Black or Norway rats fed 0.005% bait for 5 days

. 1 2 for 1 day 2 for 3 days 2 for 5 days 2 for 6 days
All observed until death or 10 days. 0 1 2 2 Not reported

00 157732

Coyote ( Canis latrans ) Ground squirrels fed 15 g of 0.01% bait for 3 days

. 1 4 adults for 5 days 3 sub

- adults for 5 days
All followed until death or 30 days post

treatment. 0 2 2 coyotes stopped feeding for 8 and 16 days, but resumed feeding and survived until the end of the study

. 001 62324



### 4.3. Incident Databases Review Reviews were conducted of the Ecological Incident Information System (EIIS, version 2.1.1) 11



### , the Agency’s Aggregated Incidents Reports database, and the Avian Incident Monitoring System (AIMS) 12 

### on 12/21 /2015

. I ncidents associated with bromadiolone were reported in all three databases; however, all of the 27 incidents reported in AIMS were also reported in EIIS

.

There were 187 incidents reported in EIIS in association with bromadiolone , all involved either birds or mamma ls. It appears likely that some mortalities were caused by primary exposure to bromadiolone bait and others by secondary exposure routes. Among those incidents, 124 were classified as possible (50), probable (35), or highly probable (39) in terms of the certainty of the association with bromadiolone exposure and the remaining 63 were classified as either unlikely or unrelated to bromadiolone exposure . The group of 124 (i.e., higher certaint y incidents ) occurred between 1983 and 2014 ( note : dates are not available for all incidents) and among the individual incidents, the legality of bromadiolone use was unknown for the majority (100), a registered use for 21, and a misuse for only three. The EIIS database also includes reports of residues in animals . A lthough some of these residue data were associated with the 187 incidents, residue data were also reported for animals that were not dead or moribund at the time of sampling (e.g., some samples were collected as part of a long term genetics and population study)

.
Three minor wildlife incidents were reported in the Aggregated Incidents Reports database; two occurred in 1998 and the other in 2005.

11 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/technical

- overview

- ecological

- risk

assessment

- risk

12 http: //www.abcbirds.org

### 13 The total number of actual incidents associated with the use of bromadiolone may be higher than what is reporte d to the Agency. Incidents may go unreported for a variety of reasons such as affected organisms were not found and effects were not immediately apparent or readily attributed to the use of a chemical

. As such, the absence of incident reports cannot be c onstrued as the absence of incidents and likewise the number of incident reports cannot be assumed to fully account for the actual number of incidents

.

5. Exposure Pathways of Concern There is potential for exposure to non

- target animals primarily through two different pathways: (1) animals may directly consume bait (i.e., primary exposure) or (2) animals may consume prey that have ingested bait (i.e., secondary exposure) . It is assumed that exposure may occur from both pathways for all outdoor uses ( above ground bait stations, burrow, and sewer ). Furthermore, it is assumed that indoor uses of bromadiolone may result in outdoor exposure through secondary poisoning (i.e., prey mammals obtain exposure indoors and then travel outdoors). Aquatic exposure ( i.e., uptake of dissolved bromadiolone from water) is assumed to be negligible

. 13



### Screening Imbibition Program

The Screening Imbibition Program (SIP v.1.0) 14 

### is typically used in the Problem Formulation stage of Registration Review to calculate an upper

- bound estimate of bird and mammal exposure
to a pesticide in drinking water

. Aquatic exposure to bromadiolone is assumed to be negligible; therefore, the screen was not performed.

Screening Tool for Inhalation Risk

The Screening Tool for Inhalation Ris k (STIR v.1.0) 1 4 

### was used to provide an upper

- bound estimate of exposure of birds and mammals to bromadiolone through inhalation of vapor (droplet inhalation is not applicable to bait uses) . The screening suggests that bromadiolone exposure is not likely significant enough for an inhalation risk concern. Appendix B provides model results.

6. Analysis Plan In order to address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of bromadiolone will be characterized and integrated to assess risk. This will be accomplished using a risk quotient ( RQ; ratio of exposure concentration to effects concentration) approach. Although risk is often defined as the likelihood and magnitude of adverse ecological effects, the risk quotient

- based approach does not provide a quantitative estimate of likelihood or magnitude of an adverse effect. However, as outlined in the Overview Document (USEPA, 2004), the likelihood of effects to individual organisms from particular uses of bromadiolone will be estimated using the

13 The product is not intended to be placed into or come into contact with the sewer water. T he concern for sewer

use is both in the sewer (i.e., non

- target organisms may visit sewers) and below the sewer discharge (e.g., chunks of bait blocks c ould be knocked or broken off as bait is eaten, discharged with stormwater or sewage overflow, and then consumed by non

- target organisms ) since the product is not required to be confined in a secured bait station.

14 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/models

- p esticide

- risk

- assessment

### 14 probit dose

- response slope and either the level of concern or actual calculated risk quotient value.

This analysis plan will be revisited and may be revised depending upon a full review of the data available in the open literature and the information submitted by the public i n response to the opening of the Registration Review docket.

6.1. Stressors of Concern Ecological Risk Assessment

Bromadiolone will be considered the stressor of concern in the ERA.

T wo major degradates (forming > 10% of applied bromadiolone) were identified in the aerobic soil metabolism study (metabolite 1; 1,3

- diphenyl

- 5(4 ’

- bromo

- bi phenyl pentane

- 1

- ol and metabolite 3; 1,3

- diphenyl

- 5(4 ’

- bromo

- bi phenyl pentane

- 1,5

- diol). Risk from exposure to these degradates is not considered a concern because the main risk concern is expected to be attributed
to primary exposure from direct consumption of bait products and secondary exposure from consumption of prey that ingested bait. Furthermore, contamin ation of soil and water from use of bait products is expected to be minimal. Therefore, the degradation products are not considered stressors of concern for the risk assessment.

Drinking Water Assessment

Drinking water degradates of concern have not bee n identified

. EFED does not anticipate conducting a drinking water assessment b ecause exposure is expected to be minima l

. 6.2. Measures of Exposure

Outdoor uses of b romadiolone will be modeled using the maximum concentrations of bromadiolone in bait and maximum residues in animals that ingested bromadiolone.

The most current models and methodologies will be used at the time of the risk assessment.

Aquatic Exposure

Potential for aquatic exposure is assumed negligible based on the use patterns ; there fore, EFED does not anticipate conducting an aquatic risk assessment.

Terrestrial Exposure

There is potential for exposure to non

- target animals primarily through two different pathways: (1) animals may directly consume bait (i.e., primary exposure) or (2) animals may consume prey that have ingested bait (i.e., secondary exposure)

. EFED does not currently have specific models for these exposure pathways ; nonetheless, exposure can be estimated from product information, empirical residue data, and assumpt ions about the non

- target animals.

### 15 Exposure from primary consumption will be estimated on both a dose and dietary basis using the concentration of bromadiolone in the formulated bait (dietary and dose concentration s ) and information about the body weigh t and food consumption rates of the non

- target animal (dose concentration)

.

S econdary exposure will be estimated in a similar way (dose and dietary

- based concentrations ); however, residues in the prey will be used instead of bait concentrations . One ap proach is to use empirical bromadiolone residue data

. Three studies are available that measured residues in tissues of animals that ingested bromadiolone (MRID 48590803, 48590 801, and 00162324/ 00162325) ; the highest whole

- body average residue was 1.83 ± 0.96 mg ai/kg

- carcass

. Those studies as well as any in the open literature will be considered when estimating potential secondary exposure.

Primary and secondary exposure will be estimated for single feedings and for multiple feedings over a period of consecutive days. This is because b romadiolone may provide a lethal dose after a single feeding; however, death is usually delayed for a period of days . Therefore, animals may continue to consume bait for several days before dying and may potentially receive a total dose that exceed s the lethal dose. Furthermore, repeated sublethal exposure may result in the accumulation of a lethal dose given that bromadiolone is expected to accumulate and be retained for a period of time in the liver. Single feeding and multiple feeding e xposure estimates will be estimated in a similar way except that multiple feeding exposure estimates will incorporate broma diolone elimination using the longest available half

- life value in liver (MRID 42596801 15 

### ). The risk assessment may further characterize risk using any additional half

- life data that are available.

Exposure to terrestrial plants is possible but unlikely and considered negligible given the use pattern (above

- ground outdoor use contained in a bait box, below

- ground outdoor use in burrows , and sewers)

.

6.3. Measures of Effect Toxicity effects data will be used as measures of direct and indirect effects to biological receptors (USEPA, 2004). As discussed previously, data will be obtained from registrant

submitted studies and from literature studies identified in ECOTOX.

Quantitative assessment of risks will be based on study endpoints that can be directly linked to the Agency’s assessment endpoints of impaired survival, growth, and reproduction. Sub

- lethal effects ( e.g. , lethargy and changes in coloration) will be evaluated qualitatively. Available incident data will be used to further characterize risk.

6.4. Integration of Exposure and Effects The exposure and effects data will be integrated in order to evaluate potential adverse ecological effects on non

- target species. The risk quotient method will be used to compare exposure and measured toxicity val ues. EECs will be divided by acute and chronic toxicity values. The

15 The available study showed a bi

- exponenti al decline of bromadiolone residues in the liver. The t 1/2 = 17 days for the first 28 days after dosing and the t 1/2 = 318 days including the period following the first 28 days after dosing.

### 16 resulting RQs will be compared to the Agency’s Levels of Concern (LOC) (USEPA, 2004). Additional metrics may be used to characterize the likelihood of mortality to non

- target organisms.

6.5. Endangered Species Assessments Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report 16 

### outlines recommendations on sp ecific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services (U.S. Fish and Wildlife Service and Nationa l Marine Fisheries ) must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to bromadiolone in connection with the development of its final registration review decision for bromadiolone

.
In November 2013, EPA, the Servi ces , and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper

, Interim Approach es for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report. 17



### Given that the agencies are continuing to develop and work toward implementation of the Interim Appro aches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for bromadiolone does not describe the specific ESA analysis, including effe cts determinations for specific listed species or designated critical habitat, to be conducted during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of bromadiolone will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods w ill be applied to subsequent analyses of bromadiolone as part of completing this registration review.

16 http://www.nap.edu/catalog/18344/assessing

- risks

- to

- endangered

- and

- threatened

- species

- from

- pesticides

17 http://www2.epa.gov/endangered

- species/interim

- approaches

- pesticide

- endangered

- species

- act

- assessments

based

- nas

- report

### 17 6.6. Endocrine Disruptor Screening As required by Federal Food, Drug and Cosmetic Act (FFDCA) section 408(p), bromadiolone is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP)

. 18


### Bromadiolone was not in the first group of pesticide active ingredients screened under the EDSP.

6.7. Drinking Water Assessment A drinking water assessment will not be performed for the Registration Review of bromadiolone b ecause exposure through drinking water is expected to be minimal

. There has never been a drinking water assessment performed for bromadiolone.

6.8. Preliminary Identification of Data Gaps

Available studies submitted t o fulfill environmental fate and ecological effects guideline requirements, as well as outstanding data gaps for bromadiolone are defined in Sections 6.8.1 and 6.8.2 , respectively. Studies are i dentified that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support the risk assessment.

6.8.1. Environmental Fate Data Environmental fate data gaps for bromadiolone are indicated in the table below ( Table 6 )

. There are many data gaps identified, but the exposure modeling envisioned for the ecological risk assessment would not benefit from requesting additional data at this time.

T able 6 . Environmental Fate Data and Data Gaps for Bromadiolone

Guideline Descrip tion MRID Classification Data Gap? Comments 835.2120 Hydrolysis 42237501 Acceptable No 1 Studies are not recommended at this time because aquatic
exposure is assumed negligible

.

2 Studies are not recommended at this time because terrestrial exposure estimates are assume d to be either non

- degraded bait, measured residues in tissues of animals that ingested bromadiolone, or estimated residues in tissues of animals that ingested bromadiolone

. In the case of estimated residues, half

lives in liver will be used to account for degradation. 835.2240 Aqueous photolysis - - Yes 1

835.2410 Soil photolysis

- - Yes 2
835.4100 Aerobic soil metabolism 43594301 Acceptable for the one soil assessed. A total of four

soils are needed to satisfy the data

requirement Yes 1 ,2

835.4200 Anaerobic soil metabolism - - Yes 2

835.4300 Aerobic aquatic metabolism - - Yes 1

835.4400 Anaerobic aquatic metabolism - - Yes 1

18 http://www2.epa.gov/endocrine

- disruption

### 18 Guideline Descrip tion MRID Classification Data Gap? Comments 835.1230 835.1240 Adsorption/ desorption and leaching - - Yes 1

835.6100 Terrestrial field dissipation - - Yes 2

835.6 2 00 Aquatic field dissipation - - Yes 1

850.6100 Analytical method in soil - - Yes 2

Analytical method in water - - Yes 1

850.1730 Fish bioconcentration 00161965 Supplemental No

BOLD = Recommended Studies



### 6.8.2. Ecological Effects Data

D ata gaps for bromadiolone remain ( Tables 7 , 8 , and 9 ) ; however, some of these studies are anticipated to have little impact on the risk assessment and are not recommended for a DCI

. EFED recommends requesting the following studies to reduce uncertainty in the risk assessment:

• 850.2100: Avian oral toxicity (passerine species) (bromadiolone; TGAI) 19



### • 850.2300: Avian reproduction (upland game species) (bromadiolone; TGAI)

• 850.2300: Avian reproduction (waterfowl species) (bromadiolone; TGAI)

In addition, non

- guideline data on toxicity to terrestrial invertebrates other than the honeybee may be useful for reducing uncertainty in the risk assessment.

T oxicity data from other sources ( e.g. , other anti coagulants) may be used in the absence of data for bromadiolone. Use of surrogate data may over or underestimate risk of bromadiolone use.

Table 7 . Ecological Effects Data Requirements (TGAI) for Aquatic Organisms Exposed to Bromadiolone and Data Gaps A

Guideline Description MRID Classification Data Gap? Comments

850.1075 Acute freshwater fish toxicity (cold water species) 00070140 Acceptable 1 No 1 In some cases an older classification scheme was reported in the DER. Studies classified as “core” are equivalent to “acceptable”.

2 Studies are not recommended at this time Acute freshwater fish toxicity (warm water species) 00070141 Acceptable 1 No

Acute estuarine/ marine fish toxicity - - Yes 2

19 The observation period should be extended beyond that of a standard 850.2100 study (14 days) given that effects from bromadiolone poisoning are not immediate (i.e., it should be long enough to capture effects of bromadiolone poisoning and continue until evidence of toxicity has subsided).

### 19 Guideline Description MRID Classification Data Gap? Comments

850.1010 Acute toxicity to freshwater invertebrates 00070685 42093302 Acceptable 1 Acceptable 1 No because potential exposure is assumed negligible based on the use pattern.

850.1025 Acute estuarine/ marine mollusk toxicity - - Yes 2

850.1035 Acute estuarine/ marine invertebrate toxicity - - Yes 2

850.1300 Freshwater invertebrate life cycle - - Yes 2

850.1350 Saltwater invertebrate life cycle - - Yes 2

850.1400 Freshwater fish early life stage - - Yes 2

Saltwater fish early life stage - - Yes 2

850.1500 Freshwater fish life cycle - - No

Saltwater fish life cycle

- - No

850.1735 Whole sediment acute toxicity, freshwater invertebrates - - No

850.1740 Whole sediment chronic toxicity, marine invertebrates - - Yes 2

- Whole sediment chronic toxicity, freshwater invertebrates - - Yes 2

- Whole sediment chronic toxicity, marine

- estuarine

invertebrates - - Yes 2

850.5400 A Aquatic plant growth (freshwater green alga) - - Yes 2

Aquatic plant growth (freshwater diatom) - - Yes 2

Aquatic plant growth

(saltwater diatom) - - Yes 2

850.5400 A Aquatic plant growth (Cyanobacteria) - - Yes 2

### 20 Guideline Description MRID Classification Data Gap? Comments

850.4400 A Aquatic plant growth (vascular plants) - - Yes 2

A As of July 2012 the new guideline numbers are 850.4500 (Algal toxicity) and 850.4550 (Cyanobacteria toxicity) BOLD = Recommended Studies



### Table 8 . Ecological Effects Data Requirements (TGAI) for Terrestrial Animals Exposed to Bromadiolone and Data Gaps A

Guideline Description MRID Classification Data Gap? Comments

850.2100 Avian acute oral toxicity (upland game or waterfowl species) 00143279 44000201 Acceptable 1 In Review No 1 In some cases an older classification scheme was reported in the DER. Studies classified as “core” are equivalent to “acceptable”.

2 Additional studies are available with less sensitive endpoints (Accession #249995; supplemental for bobwhite quail and acceptable for mallard duck). Another study (MRID 44000202, un

reviewed) is available for mallard duck; however, a cursory review of th e data indicates that the observed pattern of mortality is not suitable for calculation of a LC 50 value.

3 Studies are not recommended at this time because potential exposure is considered negligible for insect pollinators given the use pattern (sewers,

a bove ground outdoors contained in bait boxes, and below ground outdoors). Avian acute oral toxicity (passerine species) - - Yes

850.2200 Avian dietary toxicity (upland game species) 00143280 2 Acceptable 1 No

Avian dietary toxicity (waterfowl

species) 00143278 2 Acceptable 1 No

850.2300 Avian reproduction (upland game species) - - Yes

850.2300 Avian reproduction

(waterfowl

species) - - Yes

850.3020 Adult honeybee

acute contact toxicity (Tier 1) - - Yes 3

Non

- guideline Adult honeybee acute oral toxicity (Tier 1) - - Yes 3 ,4

Non

- guideline Adult honeybee chronic oral toxicity (Tier 1) - - Yes 3 ,4

Non

- guideline Larval honeybee acute and chronic oral toxicity

(Tier 1) - - Yes 3

### 21 Guideline Description MRID Classification Data Gap? Comments

Non

- guideline Residue in pollen and nectar (recommendation

pending risks identified in Tier I

studies) (Tier II) - - Yes 3 4 Non

- guideline data on toxicity to terrestrial invertebrates other than the honeybee may be useful for reducing uncertainty in the risk
assessment. T here is evidence to suggest that toxicity may occur and that the exposure pathway for exposure is complete for certain types of invertebrates

. Evidence has been documented of terrestrial invertebrates

co nsuming bait containing an anti coagulant rodenticide and excreting it (Fisher et al., 2007; H ernandez

Moreno et al., 2013). Furthermore a recent study demonstrated bromadiolone toxicity to earthworms (Liu et al., 2015)

. Non

- guideline Semi

- field testing for pollinators

(tunnel and feeding studies) (recommendation

pending risks identified in Tier I

studies) (Tier II) - - Yes 3

850.3040 Full

- field testing for pollinators (recommendation pending risk identified in Tier II studies) (Tier III)

- - Yes 3

A In some cases invalid studies were submitted [ avian oral toxicity (Accession # 232566 and MRID 00150982/40101801); avian dietary toxicity with an upland game species (MRID 00088019 and 40101801 ) and a waterfowl species (MRID 00088020 )] but valid studies are also available

. BOLD = Reco mmended Studies



### Table 9 . Ecological Effects Data Requirements (TEP) for Plants Exposed to Bromadiolone and Data Gaps

Guideline Description MRID Classification Data Gap? Comments

850.4100 A Terrestrial plant toxicity (Tier I or Tier II seedling emergence) - - Yes 1 1 Studies are not recommended at this time because potential exposure is assumed negligible based on the use pattern.

850.4150 B Terrestrial plant toxicity (Tier I or Tier

II vegetative vigor) - - Yes 1

A As of July 2012 the Final Guideline 850.4100 contains both Tier I and Tier II test guidance.

B As of July 2012 the Final Guideline 850.4150 contains both Tier I and Tier II test guidance. BOLD = Recommended Studies

### 22 7. References
Cox, P. and R.H. Smith. 1992. Rodenticide E cotoxicology: P re

- lethal E ffects of A nticoagulants

on R at B ehavior. Proceedings of the Vertebrate Pest Conference 15:165

- 170.

Fisher, P., Spurr, E., Ogilvie, S., and Eason, C. 2007. Bait C onsumption and R esidual C oncentrations of D iphacinone in the Wellington T ree W eta ( Hemideina crassidens ) (Orthoptera: Anostostomatidae). New Zealand Journal of Ecology 31(1): 104

- 110.

Hernandez

- Moreno, D., de la Casa

- Resino, I., Lopez

- Beceiro, A., Fidalgo, L., Soler, F., Perez

L opez, M. 2013. Secondary P oisoning of N on

- target A nimals in an Ornithological Zoo in Galicia (NW Spain) with A nticoagulant R odenticides: A C ase R eport . Veterinarni Medicina, 58 (10): 553

– 559.

Liu

, J., Xiong, K., Ye, X., Zhang, J., Yang, Y., Ji, L. 2015. To xicity and B ioaccumulation of B romadiolone to E arthworm ( Eisenia fetida ) . Chemosphere. 135: 250

– 256.

Pelfrene, A.F. 1991. Synthetic O rganic R odenticides. Handbook of Pesticide Toxicology, vol. 3: Classes of Pesticides, pages 1271

- 1316. Academic Press, In c.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

USEPA. 2008. Risk Mitigation Decision for Ten Rodenticides. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. May 28, 2008.

USEPA. 2011. Risks of Bromadiolone Use to the Federally Threatened Alameda Whipsnake ( Masticophis lateralis euryxanthus ), the Federally Endangered Salt Marsh Harvest Mouse ( Reithrodontomys raviventris ), and the Federally Endangered San Joaquin Kit Fox ( Vulpes macrotis mutica ). Office of Pesticide Programs, U. S. Environmental Protectio n Agency.

USEPA. 2015. Bromadiolone (112001) Label Data Report

. Office of Pesticide Programs, Biological and Economic Analy sis Division. April 14

, 2015.

### 23 

## APPENDIX A

. Names and Structure s of Bromadiolone and its Major and Minor Degradates

Table A

- 1

Code Name (Synonym) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)

PARENT

Broma diolone CAS Name: 3

- [3

- (4'

- bromo[1,1'

- biphenyl]

- 4

- yl)

- 3

- hydroxy

- 1

- phenylpropyl]

- 4

- hydroxy

- 2H

- 1

- benzopyran

- 2

- one

CAS Number: 28772

- 56

- 7 Formula: C 30 H 2 3 Br O 4 MW: 527.42 SMILES: c1cc(Br) ccc1c(cc2)ccc2C(O) CC(c3ccccc3)C4=C (O)c5ccccc5OC4 (=O) Hydrolysis pH 5

42237501

NA 91.5 (30)
Hydrolysis pH 7 100 (30)
Hydrolysis pH 9 100 (30)
Aqueous
p hotolysis 00161970 Invalid

Soil
p hotolysis 00161971 Invalid

Aerobic

s oil

m etabolism 00161969 Invalid

43594301 64 (365)

A na erobic

s oil

m etabolism 00161969 Invalid

MAJOR (>10%) TRANSFORMATION PRODUCTS

Broma diolone Ketone Formula: C 30 H 21 Br O 4 MW: 525.40 SMILES: C1(O)c2c(cccc2) OC(=O)C=1C (c1ccccc1)CC(=O) c1ccc(

- c2ccc(Br) cc2)cc1 Aerobic

s oil metabolism 43594301 30.7 (7) 4.9 (365)

Metabolite 1 Formula: C 29 H 2 5 Br O MW: 469.43 SMILES: c1(

- c2ccc(CCC (c3ccccc3)C=C(O) c3ccccc3)cc2)ccc (Br)cc1 Aerobic

s oil metabolism 43594301 19.3 (120) 14.9 (365)

Metabolite 3 Formula: C 29 H 2 5 Br O 2 MW: 485.42 SMILES: c1(

- c2ccc(C(O)CC (c3ccccc3)C=C(O) c3ccccc3)cc2)ccc (Br)cc1 Aerobic

s oil metabolism 43594301 25.7 (270) 24.4 (365) O O OH OH

Br

O O OH O

Br

OH

Br

Br O O H

H

### 24 Code Name (Synonym) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length) MINOR (<10%) TRANSFORMATION PRODUCTS

Metabolite 2 Unknown Unknown Aerobic

s oil metabolism 43594301 3.0 (60) <DL (365)

Metabolite 4 Unknown Unknown Aerobic

s oil metabolism 43594301 6.4 (120) 4.4 (365)

DL = detection limit

### 25 

## APPENDIX B . STIR v.1.0 Inputs and Outputs

Table B

- 1 . Input
Application and Chemical Information

Enter Chemical Name Bromadiolone
Enter Chemical Use bait Is the Application a Spray? (enter y or n) n If Spray What Type (enter ground or air) not applicable Enter Chemical Molecular Weight (g/mole) 527.4 Enter Chemical Vapor Pressure (mmHg) 1.00E

- 08 Enter Application Rate (lb ai/acre) N/A 1
Toxicity Properties

Bird
Enter Lowest Bird Oral LD 50 (mg/kg

- bw) 170 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178
Mammal
Enter Lowest Rat Oral LD 50 (mg/kg

- bw) 0.6
Enter Lowest Rat Inhalation LC 50 (mg/L) 0.00043 2 Duration of Rat Inhalation Study (hr) 4 Enter Rat Weight (kg) 0.35

1 N/A = not applicable. Only vapor dose is applicable to bait applications and application rate does not impact estimates of vapor dose.

2 MRID 41976901



### Table B

- 2 . Output

Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 2.84E

- 04
Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 3.57E

- 05 Adjusted Inhalation LD 50 4.90E

- 01 Ratio of Vapor Dose to Adjusted Inhalation LD 50 7.29E

- 05 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 not applicable Not applicable

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 2.84E

- 04
Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 4.48E

- 05 Adjusted Inhalation LD 50 2.56E

- 02 Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.75E

- 03 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 not applicable Not applicable