UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFET Y 

AN D POLLUTION PREVENTION 

MEMORANDUM 

DATE: March 14, 2016 

SUBJECT: Bromadiolone. Human Health Seeping Document in Support of Registration Review. 

PC Code: 112001 

Decision No.: 

DP Barcode: D429382 

Registration No.: NA 

Petition No.: NA Regulatory Action: Registration Review 

Risk Assessment Type: Seeping Document Case No.: 

TXR No.: NA CAS No.: 28772-56-7 

MRID No.: NA 40 CFR: NA 

FROM: Laura Nollen, Biologist e/~./j/- /---

Risk 

Myron 

Assessment 

S. Ottley, Senior 

Branch 

Bio

III 

l

(RAB3) 

ogist ~ 

Health Effects Division (7509P) 

THROUGH: Margarita Collantes, Biologist -lll ~ Jaime D' Agostino, Ph.D., Toxicologist .// 

Health Effects Division (7509P) 

Chri_stine_ Olinge~, Branch Chief, /)/ / .. // _ 

Registration Action Branch 3 {_Uj;?L-L .--

Health Effects Division (7509P) 

TO: Ricardo Jones, Chemical Review Manager 

Melissa Grable, Team Leader 

Risk Management and Implementation Branch 1 (RMIB 1) 

Pesticide Re-Evaluation Division (PRD) (7508P) 

As part of Registration Review, the Pesticide Reevaluation Division (PRD) has requested that the 

Health Effects Division (HED) provide a human health risk assessment seeping document for the 

rodenticide, bromadiolone. The most recent HED assessment for bromadiolone is the HED 

Chapter of the Reregistration Eligibility Decision (RED) and the RED addendum that were 

completed in 1995 and 1996, respectively (J. Redden, 9/2711995; J. Redden, 4/4/1996). 

Page 1 of 31 
Executive Summary 

Following is the Health Effects Division's (l-I ED's) human health scoping document to support 

Registration Review for the rodenticide bromadiolone, 21-1-1-Benzopyran-2-one, 3-[3-( 4'-

bromo[I, I '-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-. To evaluate the scope of 

work necessary to support Registration Review, HED has considered previous risk assessments 

for bromadiolone; updates to its toxicity, exposure and usage databases; and the latest Agency 

science policy and risk assessment methodologies. 

Bromadiolone is a second generation anticoagulant rodenticide which inhibits coagulation 

synthesis, resulting in bleeding and eventual death in target pests, such as rats and mice. This 

mechanism of action has been established in humans. 

Bromadiolone is registered to control Norway rats (including warfarin-resistant rats), roof rats 

and house mice and is fonnulated into numerous baits in ready-to use (RTU) place packs, blocks, 

chunks, paraffin pellets, traditional meals, cakes, slabs and pastes. All end-use products for 

bromadiolone contain 0.005% active ingredient (ai) by weight and are intended for 

occupational/professional use only. For all second-generation anti-coagulant rodenticides, 

consumer-use products (i.e., products~ 1 lb) containing bromadiolone are prohibited. 

Professional/commercial uses of second-generation anticoagulants require bait stations for all 

outdoor and above-ground placements and for indoor placements where children, wildlife or 

domestic animals may be exposed. Furthermore, labels prohibit broadcast application of pellet 

baits. Bromadiolone is marketed in a minimum of 8 pound (lb) units for use in and around 

agricultw-al buildings and a minimum of 16 lb units for use in and around 

industriaVcommercial/residential buildings (ships, trains, aircraft, homes or temporary 

residences, related port/terminal buildings. trash receptacles, food processing facilities or 

sewers). Bromadiolone restricts application within 50 to 100 feet of man-made structures, 

depending on the end-use product. All labels require that handlers wear shoes plus socks and 

gloves, at a minimum, and wear waterproof gloves when retrieving unused bait or when 

disposing of rodent carcasses. 

The bromadiolone toxicology database is not considered adequate for risk assessment of the 

currently-registered bromadiolone formulations and use patterns. Specifically, subchronic dermal 

and inhalation studies are needed to address the potential toxicity following occupational dermal 

and inhalation exposures. ln addition, the Revised Part 158 Data Requirements call for the 

following studies to be included in the toxicity database: acute and subchronic neurotoxicity, 

reproduction and fertility, and immunotoxicity. However, the requirements for these studies have 

been waived (TXR0057326). 

The primary toxicity resulting fTom bromadiolone exposure is hemorrhage in many internal 

organs such as the spleen, kidney, lungs, gastrointestinal (GI) tract; and external bleeding 

through the nose, vagina and nail beds. Effects included death, and were observed in rats, dogs 

and/or rabbits. 

Page 2 of 31 
The Reregistration Eligibility Decision document (RED) for bromadiolone did not quantify 

dietary (food and drinking water) exposures because of the limited use pattern (strictly non-food 

rodenticide use with no dietary exposure). 

As part of Registration Review, the toxicity endpoints, Points of Departure (PODs), and 

uncertainty factors (UFs) will be re-evaluated for bromadiolone according to cunent HED 

approaches in hazard characterization. 

Residential adult handler exposures and post-application exposures to adults or children are not 

expected, as bromadiolone consumer-based products are prohibited and any uses with the 

potential for residential or child access (e.g., above-ground uses or around residential areas) 

require the use of tamper-resistant bait stations. Therefore, residential handler and postapplication exposures will not be assessed during Registration Review. Residential bystander 

exposures resulting from off-site transport (i.e., spray drift or volatilization) are not anticipated, 

due to the registered formulations of bromadiolone. 

Occupational handlers may be exposed via the dermal and inhalation routes from the registered 

uses of bromadiolone as they fill/refill bait stations or distribute bromadiolone bait products into 

rodent burrows or sewers. Shor1-term dermal and inhalation occupational handler exposure 

assessments are expected during Registration Review based on the potential exposure to handlers 

(loaders, applicators) during the application of pelleted, meal bait or paste formulations of 

bromadiolone. Exposure to other bromadiolone products formulated as RTU baits, cakes, blocks, 

or other wax/paraffin-based formulations are considered to result in negligible exposures. 

Occupational post-application exposure is not expected from bromadiolone registered use 

patterns. At the time of Registration Review and based upon the reevaluation of toxicity 

endpoints, PODs, and uncertainty factors, HED will determine the specific appropriate 

occupational handler exposure risk assessments to conduct for bromadiolone. 

Introduction 

Bromadiolone, a coumarin, is a second-generation anticoagulant rodenticide. It is fonnulated into 

numerous bait formulations such as RTU place packs, blocks, bulk paraffin pellets, cakes, pastes and 

meal baits (e.g., EPA Reg. Nos. 270-372 and 12455-34). Bromadiolone end-use products contain 

0.005% ai by weight, and labeled target pests are Norway rats (including warfarin-resistant), roof 

rats and house mice. Registered bromadiolone use sites include in and within 50 to 100 feet of homes 

and other permanent or temporary residences, food processing facilities, industrial and commercial 

buildings, trash receptacles, agricultural and public buildings, transport vehicles (ships, trains), docks 

and other port oftern1inal buildings and related structures associated with these sites. Some products 

also allow sewer treatments, as well as rodent burrow baiting. 

Bromadiolone application rates are typically highest for rats, with calculated single maximum rates 

per treatment location around 5.0 x 10-5 lb ai. All end-use products prohibit broadcasting 

bromadiolone or applying products directly to food or feed crops. The most recent HED assessments 

for bromadiolone are the HED Chapter of the RED Document and the subsequent addendum 

completed in 1995 and 1996, respectively (J. Redden, 9/27 / 1995)(1. Redden, 4/4/ 1996). 

Page 3 of31 
ln 2008, the Agency issued a risk mitigation decision for ten rodenticides, of which 

bromadiolone was included. The mitigation decision set restrictions in order to minimize 

exposure to children, non-target wildlife and domestic animals. The risk mitigation decision does 

not apply to rodenticide fi eld (non-commensal rodents) uses or tracking powder products; 

however, bromadiolone is not registered to control non-commensal rodents, and there are no 

tracking powder products for the ai. 

The following is a summary of the 2008 mitigation that applies to second-generation 

anticoagulants, including bromadiolone: 

• Consumer-based products (~ 1 lb.): 

o Consumer-based products for second-generation anticoagulants, including 

bromadiolone, are prohibited. 

• Professional-based products 

o Must be sold in quantities of ~ 8 lbs. for second-generation anticoagulant agricultural 

building use and ~ 16 lbs. for second generation anticoagulants; above ground 

outdoor use). 

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

o Must also be placed within I 00 feet of a structure (fence and perimeter baiting 

beyond I 00 feet of a man-made structure are prohibited) when used outdoors and 

above ground, see 50 foot Document Clarification Leffer to Bell (03. 20.12) (signed) 

in docket number EPA-HQ-OPP-2006-0955-0820 found at www.regulations.gov. 

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. Loose baits/pellets/meal as a form for 

above ground outdoor uses are prohibited. 

Registered end-use products containing bromadiolone are intended for occupational use only and 

must comply with the 2008 tisk mitigation measures, as outlined above. Following review of all 

active registrations for bromadiolone, all end-use products appear to adhere to these mitigation 

stipulations. Refer to Table A.l., Use Profile for Bromadiolone (Attachment 1 ), for more 

information on the current registTations, including maximum use rates and methods of 

application for bromadiolone products. 

Refer to Attachment 2 (Table A.2.) for the chemical identity and Attachment 3 (Table A.3) for 

the physiochemical properties of bromadiolone. 

Hazard ldentificationffoxicology 

The toxicity database for bromadiolone consists of an oral 20-day study in rats, a 90-day oral 

study in dogs, prenatal developmental toxicity studies in rats and rabbits and a mutagenicity 

battery. 

Bromadiolone is a potent anticoagulant, causing a disturbance of clotting factors in the blood, 

and targeting multiple organ systems at the microgram (Jlg/kg) level in laboratory mammals. 

Observed effects were death and external bleeding (bloody urine and stools, vaginal, nasal and 

Page 4 of31 
nail bed bleeding) in rats, dogs or rabbits, and bleeding in internal organs (liver, GI tract kidneys 

spleen liver, thyroid, skin) in rats and/or dogs. Jn addition, clinical signs such as hypothermia, 

respiratory difficulties, pale mucosa, drowsiness and atonia were seen in dogs; and hypotonicity 

and pale eyes were observed in rats. Increased prothrombin time was seen in dogs. Increased 

death was observed at the high-dose level in dogs and at multiple dose levels in rats. 

The available toxic ity data do not indicate a concern for neurotoxicity, immunotoxicity or 

mutagenicity. No carcinogenicity studies were conducted, as long-term exposures are not 

anticipated for this non-food use chemical. The prenatal developmental studies in rats and rabbits 

do not indicate a concern for either toxicity or susceptibility in the offspring. 

HED has detennined the dennal absorption using a weight of the evidence approach considering 

the cuiTently available data. The physicochemical properties of bromadiolone (molecular weight 

of 527.41 g/mol and log Kow of 4.3) support a low dermal absorption. Furthermore, using the 

National Institute for Occupational Health and Safety (NIOSH) finite dose skin permeation 

calculator (http://www.cdc.gov/niosh/topics/ski n/finiteSkinPermCalc.html) and the physical 

chemical properties ofbromadiolone (see Appendix 3a for a full list), a predicted dermal 

absorption factor of 0.08% was obtained over an 8 hour period with a dermal load of 0.0872 

)..lg/cm2 (see Appendix 3b for calculations). The dermal load of 0.0872 )..lg/cm2 was derived by 

taking the expected daily exposure (95.9 )..lg) and dividing by the entire surface area of the hands 

(- II 00 cm2). The Finite Dose Skin Permeation Calculator was developed through support of a 

Center of Disease Control/National Institute for Occupational Safety and Health (CDC/NIOSH) 

grant, and provides an estimation of fluxes, skin concentrations, and amounts absorbed from any 

size dose applied to partially or fully hydrated skin, using the physicochemical properties of the 

test compound and defined exposure parameters (Kasting, G.B. 2006; Wang, T.F. 2007; Kasting, 

G.B. 2008; Miller, M.A. 2010). Currently, OPP does not rely on (Q)SAR modeling alone to 

derive a Dermal Absorption Factor (DAF) for risk assessment. However, estimates from the 

Finite Dose Skin Permeation Calculator may be used with read-across data to support a weight of 

the evidence evaluation. In addition, the European Commission's Standing Committee on 

Biocidal Products, as part of their evaluation ofbromadiolone in 2010, determined dermal 

absorption values of 1.6% in an in vitro human study. Based on a weight of the evidence 

approach, the dermal absorption ofbromadiolone is likely less than 10%; however, HED chose a 

dermal absorption value of I 0% as a conservative estimate based on the available data. 

The available pharmacokinetics data show bromadiolone is distributed to the liver where it 

accumulates (liver T 112 = 17 to 318 days in a biphasic exponential pattern). The study did not 

provide further infonnat ion on the absorption, distribution, metabolism or excretion of 

bromadiolone. 

Bromadiolone has high acute toxicity (Toxicity Category T) via the oral, dermal and inhalation 

routes. It causes minimal irritation by the dermal (Toxicity Category IV) and ocular (Toxicity 

Category Ill) routes. No data are available on dermal sensitization 

Please refer to Attachment 4 for the summary of the toxicity endpoints and PODs and 

Attachment 5 for the complete toxicity profile table for bromadiolone. 

Page 5 of31 
The available toxicity databases were evaluated for several second-generation rodenticides, 

including bromadiolone. The Hazard and Science Policy Council (HASPOC) determined that the 

following studies were not required for bromadiolone, as they were not expected to provide a 

lower POD for risk assessment: 

• 870.3800, Reproduction and fertility effects 

• 870.6200a, Acute neurotoxicity 

• 870.6200b, Subchronic neurotoxicity 

• 870.7800, Jmmunotoxicity 

Conclusions: 

The toxicology database is not adequate for risk assessment of the current registered 

formulations and use patterns for bromadiolone. Specifically, subchronic inhalation and dermal 

studies are required to address the potential toxicity following occupational inhalation or dermal 

exposure, respectively. In addition, the required (CFR Part 158) acute and subchronic 

neurotoxicity studies, a reproduction and fertility effects study and an immunotoxicity study 

have not been submitted. However, these studies are not expected to provide a lower POD; 

therefore, they are not required (TXR No. 0057384, 03/01/2015, U. Habiba). 

While a subchronic inhalation study is required for bromadiolone, the addition of a PF-5 

respirator to all active registrations for the chemical may mitigate potential inhalation exposures 

to a point where the margins of exposure (MOEs) based on the HASPOC screening criteria 

would no longer be of concern. Based on the low MOEs calculated for dermal exposure, label 

mitigation will not be a potential option to mitigate for dermal exposures and risks at this 

time. As part of Registration Review, the toxicity endpoints, PODs and uncertainty factors will 

be re-evaluated according to current HED approaches in hazard characterization. 

Residue Chemistry and Dietary Exposure 

All uses of bromadiolone are classified as non-food uses; therefore, no tolerances are established 

or needed. In addition, a dietary exposure assessment to bromadiolone from food is not needed, 

as all end-use products prohibit broadcasting bromadiolone or applying products directly to food or 

feed crops. The registered use patterns for bromadiolone are also not expected to result in dietary 

exposures to adults or children from surface or ground drinking water. 

Conclusions 

A dietary exposure assessment is not anticipated to be needed during Registration Review. 

Residential Exposure 

Residential Handlers 

Bromadiolone-containing products are intended for occupational use only. Consumer-based 

products for second-generation anticoagulants, including bromadiolone, are prohibited. 

Therefore, residential handler exposures are not expected. 

Page 6 of31 
Residential Post-Application 

Tamper resistant bait stations are required for any bait placed above ground or where children, 

pets or non-target wildlife may be present or have access. Post-application exposw·es to 

bromadiolone products placed in tamper-resistant bait stations or below ground are not 

anticipated. Therefore, a residential post-application exposure assessment is not anticipated in 

order to conclude with reasonable certainty that residential exposures to bromadiolone do not 

pose a significant human health risk. 

on-Occupational Sprav Drift or Volatilization 

Since bromadiolone is applied as a solid formulation by hand, largely in tamper-resistant bait 

stations, neither exposure from drift or volatilization is expected. 

Conclusions 

Residential exposures are not expected. Therefore, a residential handler or post-application 

assessment is not required during Registration Review. Given the formulations and registered 

uses, the Agency does not expect exposures from spray drift or volatilization. 

Aggregate 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. 

For bromadiolone, there are no dietary food exposures. Broadcast applications of bromadiolone 

and direct applications to food or feed crops are prohibited. Additionall y, bromadiolone products 

are not intended for consumer use, and any above-ground uses of bromadiolone where children 

may be exposed must be in tamper-resistant bait stations. Based on the registered uses, HED 

does not anticipate dietary (food or drinking water) or residential exposures. Therefore, an 

aggregate risk assessment is not anticipated for children or adults based on the current 

bromadiolone use pattern and formulations. 

Conclusions 

During Registration Review, an aggregate risk assessment is not required for children or adults 

based on the current bromadiolone use pattems and formu lations. 

Occupational and Commercial Exposure 

Occupational/Commercial Handler Exposure 

Handler exposures have not previously been quantitatively assessed for bromadiolone. Handlers 

may potentially be exposed by the dermal or inhalation routes in the short-tenn duration of 

exposure from: (1) placing pelleted, meal or paste bait f01mulations in burrows; (2) loading bait 

stations with meal bait or bait pellets from larger containers; and (3) securing large paraffin 

blocks at bait stations in sewers. 

It is unclear from labels and other available information the extent to which it is necessary, due 

to size or design of packages, for handlers to directly handle or contact bait during bait station 

loading, which may result in dermal exposures; or the extent to which it is possible for inhalation 

exposures to occur following contact with meal baits or pellets during bait station loading. 

Page 7 of31 
Occupational handler dermal and inhalation exposures from loading or applying bait blocks, 

cakes, slabs or other RTU formulations (e.g., placement packs) are considered to be negligible. 

Due to the nature of the registered use patterns, long-term occupational exposure is not expected. 

End-use product labels require handlers to wear gloves plus shoes and socks at a minimum when 

applying bromadiolone, and waterproof gloves when handling used bait or rodent carcasses. 

Most labels also require handlers to wear long-sleeved shirts and long pants. 

The 1995 HED RED chapter did not establish a POD to estimate occupational handler risks. 

Therefore, HED recommends using the maternal no-observed-adverse-effect level (NOAEL) of 

0.004 mg!kg/day from the rabbit prenatal developmental toxicity study maternal based on an 

increased incidence of vaginal bleeding at the maternallowest-observed-advcrse-effect level 

(LOAEL) of0.008 mg/kg/day. During Registration Review, the Agency will conduct a revised 

handler exposure assessments using updated policies and body weight assumptions. 

Occupational/Commercial Post-Application Exposure 

Based on the current use patterns and approved registrations for bromadiolone, there are no 

anticipated occupational or commercial post-application exposures. All post-application 

activities (e.g., removing dead rodent carcasses) for bromadiolone include the requirement of 

waterproof gloves; therefore, exposures are expected to be negligible. 

Conclusions 

Based on the use sites and active registrations for bromadiolone, short-term occupational handler 

dermal and inhalation exposures are expected. During Registration Review, HED will reevaluate 

the points of departure, toxicity endpoints, and uncertainty factors used for risk assessment 

purposes. Based upon that infonnation, and using updated policies and body weight assumptions, 

HED will conduct a handler exposure assessment for bromadiolone. Occupational postapplication exposures are not anticipated for bromadiolone. 

Additional information regarding the maximum number of refillable mouse and rat trap/bait 

stations within the 50 or I 00 foot perimeter of buildings may allow HED to better estimate 

potential occupational handler exposure and risks. 

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' PRD 

requested an analysis of human incidents involving exposure to rodenticides in 2011 (D395567, 

S. Recore, 10/28/2011) and updated in 2015 (D430176, S. Recore, 111 17/2015). For this 

evaluation. the Agency consulted the OPP Incident Data System (IDS), the National Pesticide 

Information Center (NPIC). 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 Agricultural Health Study (AHS) databases for 

pesticide incident data on the active ingredient bromadiolone. 

Page 8 of31 
For the Main IDS, which contains incidents resulting in higher severity outcomes (i.e., death, 

major and moderate incidents) from January 1, 20 10 to May 27,2015, from January 1, 2010 to 

May 27, 2015, there were 12 incidents reported for the single chemical bromadiolone in the 

database. Eleven of these incidents were classified as moderate severity and one of these 

incidents was classified as major severity. An incident description classified as major severity 

involved several children who were hospitalized after coming into contact with bromadiolone. 

Bromadiolone was placed atop a high filing cabinet in a classroom, and children accessed the 

a.i., which they mistook for candy. In Aggregate IDS, from January l, 2010 to May 27, 2015, 

there were 171 incidents reported involving bromadiolone. Fifty two incidents were classified as 

having no or unknown effects, and 119 incidents were classified as minor severity. 

A query of SENSOR-Pesticides from 1998-201 1 identified a total of 15 cases involving 

bromadiolone. Of these, ten cases involved a single active ingredient bromadiolone. One case 

was high severity, two cases were moderate severity and seven cases were low severity. Four 

cases were intentional ingestion for self-harm. These four intentional cases include the high 

severity case and both moderate severity cases as well as one low severity case. 

The Agency will continue to monitor the incident information and provide an updated review of 

incidents, considering pre- and post-mitigation incidents separately, when the information 

becomes available. 

Tolerance Assessment and International Harmonization 

There are no tolerances for bromadiolone, and thus no concerns with regard to international 

harmonization. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, will be considered 

during Registration Review, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.archives.gov/federal-register/executive-orders/pdf/12898.pdQ. As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, l-IED 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-application 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 oftoxicity finding as 

to bromadio1one and any other substances and bromadiolone 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 

Page 9 of31 
such chemicals, see the 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:/h.nvw.epa.gov/pesticidcs/cumulative/. 

Human Studies 

The risk assessments HED anticipates to conduct during Registration Review for bromadiolone 

will rely in part on data from studies in which adult human subjects were intentionally exposed 

to a pesticide to determine their dermal and inhalation exposure. Many of these studies, 

involving exposure to many different pesticides, comprise generic pesticide exposure databases 

such as the Pesticide Handlers Exposure Database (PHED), the Agricultural Handler Exposure 

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 any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA's Rule for the 

Protection of Human Subjects of Research, Title 40 of the Code of Federal Regulations (CFR) 

Part 26, have been satisfied, and there is no regulatory barrier to continued reli ance on these 

studies. 

Data Deficiencies 

The following toxicology data are needed to support the registered uses of bromadioJone: 

• A subchronic dermal toxicity study (§870.3200) 

• A subchronic inhalation toxicity study (§870.3465) 

Page 10 of31 
References 

Habiba, J. Rodenticides: Summary of Hazard and Science Policy Council (HASPOC) Meeting 

on October 1, 2015: Recommendations on Data Requirements for Rodenticides. TXR #0057326. 

12115/2015. 

Kasting, G. B. and M.A. Miller (2006). "Kinetics offinite dose absorption through skin 2. 

Volatile compounds." Journal of Pharmaceutical Sciences 95(2): 268-280. 

Kasting, G. B., M.A. Miller, et al. (2008). "A Spreadsheet-Based Method for Estimating the 

Skin Disposition ofVolatile Compounds: Application to N,N-Diethyl-m-Toluamide (DEET)." 

Journal of Occupational and Environmental Hygiene 5(1 0): 633-644. 

Wang, T.-F., G. B. Kasting, et al. (2007). "A multi-phase microscopic model for stratum 

corneum permeability. II. Estimation of physicochemical parameters and application to a large 

permeability database." Journal of Pharmaceutical Sciences 96(11 ): 3024-3051. 

Miller, M.A. and G. B. Kasting (201 0). "Toward a Better Understanding of Pesticide Dermal 

Absorption: Diffusion Model Analysis ofParathion Absorption in Vitro and in Vivo." Journal of 

Toxicology and Environmental Health 73(4): 284- 300. 

Recore, S. Rodenticide: Tier I (Seeping) Review of Human Incidents and Epidemiology 

Assessment. D426573. 11/24/2015. 

Recore, S. Rodenticides Tier II: Review of Human Incidents. D395567. 10/28/2011. 

Redden, J. The HED Chapter of the Reregistration Eligibility Decision (R Document ED) for 

Bromadiolone. Case No. 2760; Chemical No. I 12001. 09/27/1995 

Redden, J. RED Chapter Addendum to the HED Chapter of the Reregistration Eligibility 

Decision Document (RED) for Bromadiolone. Case No. 2760; Chemical No. 112001. 

04/04/1996 

Attachments 

1. Use Profile 

2. Chemical Identity Table 

3. Physicochemical Prope11ies ofTechnical Grade Bromadiolone Table 

4. Endpoint Selection Table 

5. Toxicity Profile Tables 

6. Toxicology Data Requirements Table 

Page 11 of 31 
Attachment 1 

Table A. I. Use Profile for Bromad iolonc. 

Occupational. Max. 

EPA Product % Active Application 

Exposure Application 

Reg. Name Formulation2 

Ingredient Use Sites Target Pests PPE/Ciothing3 methods

4 Expected? Rate/location.-

No.

1 YIN Rats 

(Rationale) 

Bromadiolone 

270-371 2.5% NA 2.500% NA NA NA NA N (Not lind-use) NA 

Concentmte 

In and around 

Agri cultuml 

llromudiolone RTU place Buildings; Industrial Norway rats Rats- 1.5 oz. and comrncrcinl {incl. warfarin270-372 Bait Pellets/Just packs 0.005% buildings: inside resistant), roof LSS. LP. SS. WG place packs. 3-10 N (RTU Place 0.00005 One llitc II containing ships. trains, aircraft rats. house packs. Mice- I pncks) 

Place Packs pellets ( 1.5 oz.) and rclmcd mice pack 

ponltenninnl 

buildings 

Burrows. nmways. 

hard-to-reach areas: 

Orornadiolone In and around Agri. Norway rats 

Bait Bar: Just Wrapped bait Buildings and (incl. warfarin- Rats- 2 oz. bars. 

270-373 one Bite II bar: bar/chunks (2 0.005% lndustrial/commcrci:tl resistant), roof LSS, LP. SS. WG 2-8 (burrows N (Wrapped 0.00005 

Just one Bite II oz.) buildings including rats. house lower rate). Mice- bait) 

Bait Chunks transport vehicles mice I bar 

(ships, trains. 

aircra11). pon or 

terminal buildings 

Maki 

7173- 173 Rodenticide NA 1.000% NA NA NA NA N (not End-usc) NA 1.0% Dry 

Concentrate 

7173-174 Maki Technical NA 98.500% NA NA NA NA N (Not End-usc) NA 

Indoor/Outdoor: 

Homes. food Norway rats processing faci l itics. Maki Paraffin Pellets commercial buildings. (incl. warfarin- Rats- 4-1 6 oz. 7173-1 87 Paraninized 0.005% resistant), roof LSS. LP. SS. WG Y (loose pellets) 0.00005 

Pellets (bulk) Ag. buildings, rats. house Mice- 1/4-2 oz. 

transport vehicles. mice docks/pon/tcmtinul 

buildings: trash cnns 

Maki Rat and RTU Bait place No burrows: llomcs. Norway rats Rats- 15 oz. 

food processing packs. 3-10 N (RTU Place 7173- 188 Mouse Bait packs (paraffin 0.005% facilities. (incl. warfarin- LSS, LP. SS. WG 

packs. Mice- 1-3 packs or pellets) 0.00047 

Packs (Pellets) pellets) ( 15 oz.) industrial/commercial resistant). roof 

packs - ----·---

Page 12 of 3l 
Table A. I. Use Profile for Bromadiolone. 

Occupational. Max. ' EPA Product % Active Application Exposure Application 

Reg. Name Formulation2 

Ingredient Use Sites Target Pests PPE/Ciothing3 methods4 Expected? Rate/location.-

No. 1 YIN Rats 

(Rationale) 

buildings, trashcans. rats, house 

ag, transpon vehicles. mice 

docks. pons. 

terminals. etc. 

No burrows; homes. 

food processing Norway rats Rats- 2 oz. 

facil itics, (incl. warfarin- pieces. 2-8 pieces 

7173-189 Maki Paramn Hau bars(llb, 0.005% industrial/commercial resistant). roof LSS, LP_. SS. WG (Sewer- I entire N (Bait blocks) 0.00005 I 

Blocks 2 0'-) buildings, trashcans. rats. house block on wire on 

ag, mmspon vehicles. mice manhole). Micedocks, pons, I piece 

tenninals. etc. 

No burrows: homes. Rats- 28 g blocks. 

food processing 

3-16 blocks 

facilities. Norway rats (Sewer- I block 

Maki Mini Bait Blocks induslrial/commercial (incl. warfarin- on wire on 

7173-202 Blocks (28g) 0.005% buildings, trashcans, resistant). roof I.SS, LP, SS, WG manhole above N (Bait blocks) 0.00005 

nus, house high water line or ng, transpon vehicles, mice on board: 16 docks, pons, blocks/manhole). tenninals. etc. Mice- 1-2 blocks 

No burro\\ s: homes. 

food processing Norway rats Maki facil itics, Cannot calcuhue: 

Rodcruicidc RTU 13uit Pucks industrial/commercial (incl. warfarin- Rats- 4-16 packs. N (RTU Place negligible 7173-208 0.005% resistant), roof LSS. LP, SS, WG Bail Packs (pellets) (NS} buildings, lrashcans. rats. house M icc- 1-4 packs packs) exposure 

(Pellets) ag. trnnspon vehicles. mice expected 

docks. pons. 

tenn inals. etc. 

llorncs, food 

processing faci lities, Norway nns 

Maki Paramn Pellets industriallcommcrci al (incl. warfarin- Rats· 4-16 oz. Y (loose parnllin 7173-212 Rodenticide 0.005% buildings, trashcans. rcsistalll). roof LSS. LP, SS. WG pellets. Mice- 0.00005 

Pellets: (bulk} ag. transpon vehicles, rats. house lf.t-2 oz. pellets) 

docks. pons . mice 

lcnninals. ete. 

No burrows: homes. Norway rats Rats- 28 g blocks. 

Maki food processing (incl. warfarin- 3-16 blocks 

7173-215 Rodenticide Mini Olocks (28 0.005% facilities, resistant). roof I.SS, LP, SS, WG (Sewer- I block N (parallin 0.00005 

Mini Blocks g) industrial/commercial raL~. house on wire on blocks) 

buildings. trashcans, mice manhole 

ag. transpon vehicles. hin~t. or 

Page 13 of 31 
Table A. I. Use Profile for Bromadiolone. 

Occupational. Max. 

EPA Product % Active Application Exposure Application 

Reg. Name Formulation2 

Ingredient Use Sites Target Pests PPE/Ciothing3 methods4 Expected? Rate/location.-

No. 1 YIN Rats 

(Rationale) 

docks. pons. above high wmer 

tem1inals. elc. line or on beard, 

16 

blocks/manhole.). 

Mice· 1·2 blocks 

No burrows: homes. Rats- 0.42 oz. food processing Norway mts packs, 7-36 Y (place packs. facilities, 

Bromndiolone RTU Paste Oait i nd ust ria 1/commerc ia I (incl. warfarin- packs/pouches. bu1 paste may be 

7 173-297 Paste 0901 Packs (0.42 0.005% buildings. lrashcons, resistant), roof I.SS. LP, SS. WG Mice- 1-4 0.42 removed and 0.00005 

07../12 g) ag, transpon vehicles. rats, house 07.. placed in bait 

docks, pons. mice packs/pouches, 8- slUt ion) 

tenninals, etc. 12', 15 days: 

homes and other 

pcnnancnt or 

temporruy residences. 

food processing 

facilities. 

industrial Wld 

commercial buildings. Norway mts 

Paraffin Block trash receptacles. (incl. warfarin12455-34 ContmcAII- (lib slab with 4 0.005% agriculn.tral :md resistant). roof LSS. I.P.SS.G Rats- 4 oz. slabs. N (paraffin cake) 0.00005 

weather Cake oz. pieces) public buildings, rats, house 1-4 4 slabs 

transpon mice vehicles (ships. trains, 

aircrnfi), docks and 

pon oftcnninal 

buildings and related 

structures around and 

associated with these 

sites 

burr011 s: homes :nd 

other pem1ancm or 

temporary res idcnccs. 

food processing Norway rats 

Contmc Rat and facilities. (incl. warfarin- Rat- 3-16 oz. bait. Y (Meal bait, 12455-36 Mouse Boil Bulk Bait. Meal 0.005% industrial ru1d rcsistont), roof LSS. LP, SS. WG Mice- 1/4 to 2 oz. grains) 0.00005 

commercial buildings. rats, house bait 

trash receptacles, mice 

agricultuml ru1d 

public buildings, 

transpon 

Page 14 of31 
Table A.l. Usc Profile for Bromadiolonc. 

Occupational. Max. 

EPA Product % Active Application Exposure Application 

Reg. Name F onnu lation2 

Lngredient Use Sites Target Pests PPE/Ciothing3 

methods4 Expected? Rate/location.- No. 1 YIN Rats 

(Rationale) vehicles (ships. trains. 

aircraft), docks and 

port oftcn11 inal 

buildings and rclmed 

structures around and 

associated with these 

sites. 

burrows: homes nnd 

other pcn11ancm or 

temporary residences, 

food processing 

facilities, 

industrial and 

commercial buildings. Norway nus trash receptacles. (incl. warfarin- Rats- 4-16 oz. 12455-69 CorHrac Parallin Pellet 0.005% agricullural and resistant), roof SS.G bait. Mice- 1/4 to Y (Granular Rodenticide Bait publi 0.00005 c buildings. rats, house 2 oz. bait pellet) 

transport rni ce vehicles (ships, trains. 

aircraft), docks ru1d 

port oftem1inal 

buildings and related 

structures around and 

associated "ith these 

sites. 

12-155-70 Technical 

Orornadiolonc NA 96.500% NA NA NA NA N (Not end-usc) NA 

homes and other 

pem1anent or 

temporary residences. 

food processing 

facilities, 

industrial and Norway rats Rats- 1.5 oz. Contrnc Rat and RTU Place commercial buildings, (incl. warfarin· 12455 place packs, 2-1 0 N (RTU place ·75 Mouse 13a 0.005% trash receptacles. resistant). roof l.SS. LP. SS. WG 0.00005 it Packs (I. 5 oz.) agricullural and rats, house packs. Mice- I packs) 

public buildings, mice pack 

transport 

vehicles (ships, trains. 

aircraft). docks and 

port oftcnninal 

buildings and related 

Page 15 of31 
Table A. I. Use Profile for Bromadiolone. 

Occupational. Max. 

EPA Product %Active Application Exposure Application 

Reg. Name Formulation2 

Ingredient Use Sites Target Pests PPE/Cioth ing3 

methods4 Expected? Rate/location.-

No. 1 YIN Rats 

(Rationale) 

structures around and 

nssociated with these 

sites. 

homes and other 

pcm1anent or 

temporary residences. 

food processing 

facilities, industrial 

and commercial 

bui I dings. trash Norway rats receptacles, Rats· 1.5 oz. 

Contrac RTU Place agricultural and (incl. warfarin- place packs. 2-10 N (RTU Place 12455-76 0.005% resistant), roof SS.G 0.00005 Rodenticide Packs ( 1.5 oz.) public buildings, rats. house place packs. Pack) 

transport vehicles mice Mice- I pack 

(ships, trains. 

aircrafi), docks and 

pon oftenninal 

buildings and related 

structures around and 

associated with these 

sites. 

Industrial and 

commercial buildings. 

trnsh rcccptncles, 

agricultural ;md 

public buildings, Norway rats, Rats- I o:t. bait 

12455-79 Contrac AII- Bait Blocks (I 0.005% transport (ships. roof rats and SS.G blocks. 3-16 N (Parall]n 0.00005 Weather Blox oz.) trains. aircrafi), docks house mice blocks. Mice- 1-2 block) 

and pon of tcnninal blocks 

buildings and related 

structures around and 

associated with these 

sites. 

homes and other 

penn anent or 

temporary residences. 

Contrac Super Oait Blocks (8 food processing Norway rats. Rats- 8 oz. bait N (Paranin 12455-82 0.005% facilities, LSS. LP. SS, WG blocks, 1-2 0.00005 Size Blox oz.) industrial and roof rats blocks. block) 

commercial buildings, 

trash receptacles. 

agricultural and ---

Page 16 of 31 
Table A.J. Use Profile fo r Bromadiolone. 

Occupational. Max. 

EPA Product %Active Application Exposure Application 

Reg. Form u lation2 Use Sites Target Pests PPE/Ciothing3 Expected? Rate/location.-

No.

1 Name Ingredient methods4 

YIN Rats 

public buildings, 

(Rationale) 

transport 

vehicles (ships, trains. 

aircraft). docks and 

port of terminal 

buildings and related 

structures around and 

associated witl1 these 

sites. 

homes and other 

pennanent or 

temporary residences, 

food processing 

facilities, 

industrial and 

commercial buildings, Rat- 0.88 oz. Contrac trash receptacles, Norway nlts, place packs, 4-1 6 

12455-86 Rodemicidc RTU 13ait Place 0.005% agricultural and roof rats and SS.G place packs. N (RTU Place 0.00004 

Place Pacs packs (0.88 oz.) pub I ic buildings, house mice Mice- I place Pack) 

transport pack vehicles (ships, trains. 

aircrall), docks and 

port of tenninal 

buildings and related 

structures around and 

associated witl1 these 

sites. 

Industrial- homes and 

other pemmnent or 

temporary residences, 

food processing 

facilities, 

industrial and Norway rats commercial buildings, (incl. warfarin- Rats- I 07 .. bait 

12455-133 Contrac witl1 Bait Blocks (I 0.005% trash receptacles, resistant), roof LSS, LP. SS, WG blocks, 3-16 N (Paraffin Lurnitrack oz.) 0.00005 agricultural and rats, house blocks. Mice- 1-2 Block) pub I ic buildings, mice blocks 

transport 

vehicles (ships, trains, 

aircraft), docks and 

port of tem1inal 

buildings and related 

structures around and 

Page 17 of31 
Table A. I. Use Profile for Bromadiolonc. 

Occupational. Max. 

EPA Product % Active Application Exposure Application 

Reg. Name Formulation2 

Ingredient 

Use Sites Target Pests PPE/Clothing3 

methods

4 Expected? Rate/location.-

No. 1 YIN Rats 

(Rationale) 

associated with these 

sites. Ag- agricultural 

buildings and manmade agricu It ural 

stmctures constmctcd 

in a 

manner so as 10 be 

vulnerable to 

commensal rodent 

invasions ancVor to 

harboring or 

attracti ng rodcm 

infestations. 

Industrial- homes. 

other pcm1ancnt or 

temporary residences. 

food processing 

facilities. industrial 

and commercial 

buildings. trash 

Rat-a-rest receptacles, Norway rats, Rats· 4-16 oz. Y (Granular bulk 67517-34 Bulk Pellets 0.005% agriculturalmtd roof rats. house I.SS. LP. SS. WG bait. Mice- 1/4 to 0.00005 pellets public buildings. mice 2 oz. pellet) 

transport vehicles 

(ships. trains. 

aircraft). 

docks and pon of 

tcm1inal buildings 

Ag· I 00' of ag. 

Buildings 

Industrial- homes. 

other pcmmncrc or 

temporary residences. 

food processing 

faci lities, industrial 

Mouse-a-rest and commercial Mice- 1/4 • 2 oz. 67517-35 

pellets 13ulk Pellets 0.005% buildings, trash House mice LSS. 1.1', SS, WG bait Y (Loose pellet) 0.0000 1 

receptacles, 

agricultural ru1d 

public buildings. 

transpon vehicles 

(ships, trains. 

aircraft). 

Page 18 of 31 
Table A. I. Use Profile for Bromadiolone. 

Occupational. Max. EPA Product % Active Application Exposure Application 

Reg. Formulation2 Use Sites Target Pests PPE/Ciothing3 Expected? Rate/location.-

No.1 Name Ingredient methods4 

YIN Rats 

(Rationale) 

docks ru1d port of 

tenninal buildings. 

Industrial and 

commercial buildings. 

trash receptacles. Norway rats. Rats- I. 5 oz. 

675 17-37 Rat-mouse-a- RTU Place 0.005% agricultural and roof rats. house LSS. I.P, SS, WG packs, I 0 packs. N (RTU Place 0.00005 rest Place Pack Packs ( 1.5 0 1.) pub I ic buildings. mice Mice- I place Pack) 

transport, docks. pon pack 

oftenninal buildings, 

etc. 

In and around Norway Rats. residential buildings, Roof Rats and Rats- I oz. bait 

72500-19 Smacker Aait Wax Oait 0.005% Industrial and I louse Mice, SS.G blocks, 4-16 N (Wa.~ bait 

B 0.00005 locks (I oz.) agricultural buildings and their blocks. Mice- I block) 

ru1d similar man-made Infested neas block structures. etc. 

In and around homes 

and other pcnnaru..,ll 

or temporary 

residences. food 

processing facil itics, 

industrial m1d 

commercial buildings. 

trash Rats I oz. bait receptacles, Norway rats. blocks. 6-7 

82744-1 Rmimor Wax Wax Blocks (I 0.005% agricultural :md 

Block roof rats, house SS, CRG blocks. Mice- 1-2 N (Wax block) 0.00002 07.) public buildings. mice blocks, every 6'- transport vehicles 16' per location (ships, trains, 

aircraft). 

docks tuld pon of 

tenninal buildings 

and related Slructun.:s 

around and associated 

with these 

sites. 

homes and other 

RTU Wrapped permanent or Norway rats, Rats-0.38 oz. 

82744-2 Ratimor Soft Soft Bait Bags 0.005% temporary roof rats, house SS, CRG bait bags, I 0-42 N (RTU bait 

Bait 0.00005 residences, food bags. Mice- 1-2 bag) (0.38 oz.) processing fac ilities, mice bags 

industrial and 

Page 19 of 31 
Table A.l. Use Profile for Bromadiolooe. 

Occupational. Max. 

EPA Product %Active Application Exposure Application 

Reg. Name 

Forrnulation2 

Ingredient Use Sites Target Pests PPE/Cioth ing3 methods

4 Expected? Rate/location.-

No. 1 YIN Rats 

(Rationale) 

commercial buildings. 

trash 

rcccptnclcs, 

agricultural rutd 

public buildings, 

transport vehicles 

(ships. trains. 

aircraft), 

docks and port of 

tcnninal buildings 

and rc at~ll structures 

around and associmcd 

with these 

sites. 

Brigrutd SB Soft Wrapped Wax Industrial and Norway rats, Rats: 0.35 oz. bait N (RTU bait 87235-1 Bait Son Bait Bags 0.005% agricullurnl use sites, roof rats. house LSS. LP. SS. WG bags. I 0-42 bags. 0.00005 

Rodenticide (0.35 oz.) as others mice M icc- 1-2 bags. bag) 

Brigru1d Wl3 Industrial rutd Norway rats, 

Rats: 4-16 blocks. 

87235-2 Wa.x Block Wa.x Blocks (I 0.005% agricullural usc sites, roof rats. house I.SS. LP. SS. WG 15'-30'. I 0 days: N (13ait block) 0.00005 oz.) Mice: 1-2 block. Rodenticide as others mice 8'-12', IS days 

Bromadiolonc 

270-371 2.5% NA 2.500% NA NA NA NA N (Not EUP) NA 

Concentrate 

In and nrowtd 

Agricullural 

Bromadiolonc RTU Place Buildings: Industrial Norway rats Rats- 1.5 oz. 

Bait Pellets/Just packs and commercial (incl. warfarin- place packs. 3-10 N (RTU Place 270-372 One Bite II containing 

0.005% buildings: inside resistant). roof LSS. LP. SS. WG packs. Mice- I packs) 0.00005 

ships, trains, aircraft rnts, house Place Packs pellets ( 1.5 oz.) and related mice pack 

port/tcnninal 

buildings 

13urrO\\S, runways, 

Bromadiolonc hard-to-reach areas: Norway rats In and around Agri. Rats· 2 oz. burs, Bait Bar: Just Wrapped bait 13uildings a11d (incl. warfarin- 2-8 (burrows N (Wrapped 270-373 one ll itc II bar: bar/chunks (2 0.005% resistant), roof LSS, LP, SS, WG 0.00005 

Just one Bite II oz.) Industrial/commercial rats, house lower rate). Mice- bait) 

Bait Chunks buildings including mice I bar 

transport \'Chicles 

(shios. trains. 

Page 20 of31 
Table A. I. Use Profile for Bromadiolone. 

EPA Product %Active Application Reg. Forrnu lation2 Use Sites Target Pests PPE/Cioth ing3 

No.

1 Name Ingredient methods4 

aircraft). port or 

tcm1inal buildings 

Maid 

7173-173 Rodenticide NA 1.000% NA NA NA NA I 0% Dry 

Concentrate -

1 All end-usc products include the following restrictions: Do not apply directly to food or feed crops. Do not broadcast bromadiolonc. 2 RTU = ready-to-usc fonnulation 

Occupational. Max. 

Exposure Application 

Expected? Rate/location.-

YIN Rats 

(Rationale) 

N (not EUP) NA 

---·-··-···------ -·-- -

3 PPE = Personal protective equipment. LSS = long sleeved shirt. S = shirt. LP = long pants, SS =shoes & socks. WG = waterproof gloves. CRG = chemical-resistant gloves. G = 

gloves. All labels include a minimum of shoes and socks plus gloves. and walerproof gloves when disposing of used bait or rodent carcasses. 

~U nless otherwise stated, treatment locations for rats are to be placed every 15"-30' and treatment locations for mice arc to be placed every 8'-12 '. Treatments are to be continued 

for I 0 or 15 days (or until rodent activity ceases) for rats and mice. respectively. 

Page 21 of 31 
Attachment 2 

TABLE A.2. Bromadiolone Nomenclature. 

Chemical structure W' OH 

CHCH2CH-o-o-Br 

OH6 - -

Common name Bromadiolone 

IUPAC name 3-[3-(4'-bromobiphcnyl-4-yl)-3-hydroxy-1-phenylpropyl)-4-hydroxycoumarin 

CAS name 3-[3(( 4'-bromo-[ 1.1'-biphnyl)-4-yl)-3-hydroxy- 1-phenylpropyl]-4-hydroxy-2H-Ibenzopyran-2 one (9CI) 

3-[-[ p-( p-bromophenyl)-hydroxyphenethyl} benzyl-4-hydroxycoumarin](8CI 

CAS registry number 28772-56-7 

Page 22 of31 
Attachment 3a 

Table A.3.a. Physicochemical Properties of Bromadiolone. 

Parameter Value Reference 

Melling point 205-2 10 (0 C) 

Physical State White Powder 

Density 0.33g/cc 

olvcnt solubility (giL at 25°C) Water: 6.1 ppm: hexane: <0.0 1 g/IOOml: ethanol: 

MR!Ds 0.5 g/IOOml: dietl1)l ether: 0.0 14 g/IOOml: 

acetone: 1.15 g/IOOml 41 7 17001.41717002. 

41 7 17003,46359001. 

Vapor pressure 2 x 10-6 Pa (at 20°C) 42667801 

Dissociation constant. pK. 5. 73 in water 

Octanol/water partition coenicicnt 4.3 

Log( Pow) 

Stability 97.55% to !03.3% 

Page 23 of 31 
Attachment 3b 

Dermal Penetra tion Calcula tions 

(http://www.cdc.gov/niosh/topics/ski n/finiteSkinPermCalc.html) 

Skin Description/ Environment 

Species : HUMAN 

H ydration: Partially Hydrated 

Setting : in vivo 

T emper ature : 32.0 °C 

Wind velocity : 0.165 m/s 

Skin Properties 

Stratum 

Corneum 

Thickness (hxx)' ~tm ] 13.365 

oH 5.00 

Diffusivity (Oxx)' I [cm2

/s] 1.05£-12 

Wa ter Pa rtition 180.77 

Coefficient (Kxx!W)I 

Clearance (k,xxJw)1 [s-•] 

Unbound Fr action (fu) 

Non-ionic F r action (fnon) 

F ra ctional Deposition 0.025 

Depth (fdep) 

Time Constant (h ~/ c) [hours] 472.70 

Saturation Concentration [g/cm3

] 3.75 1E-04 

(Csat)2 

Sa tura tion dose (M~,. 3 I rug/cm2

l 0.013 

Viable 

Epidermis 

100.00 

7.40 

6.69£-08 

20.47 

0.0 

2.37E-02 

1.00 

1 XX-> SC (Stratwn Corneum), VE (Viable Epidermis), DE (Dermis). 

1 The concentration of the permeant in the stratum corneum at saturation. 

•

1 The amount ofpermeant in the deposition zone when it is saturated with the 

per meant. 

Permeant Properties 

Page 24 of 31 

Dermis 

2000.00 

7.40 

6.69E-08 

20.47 

7.53E-06 

2.37E-02 

1.00 
f •••••••••••••••••••••••••••••••••••• 

Chemical Name 

Chemical formula 

CAS# 

logKow 

Molecular weight 

Melting point 

Boiling point 

[g/mol] 

[OC] 

[OC] 

bromadialone 

C30H23Br04 

28772-56-7 

4.30 

703.120 

205.00 

723.00 

Vapour pressure I [Pa] 2.000E-06 (1.500 12334764226E-8 at 

Initial Amount 

Number of double 

bonds 

Number of triple bonds 

Number of ring systems 

Pharmacophore 

Grain class 

Effective Density (perr) 

8.72E-02 

2 

0 

5 

Absent 

Other 

1.935 

Evaporative properties 

Evaporation Rate 

Constant {kevnp) 

Evaporation/ Absorption 

R~ nrP ~tio fXcA 

Vehicle Properties 

[ern/h) 

Immobile Vehicle Not Present j ••• •• •••••••••••••••• • • ••••••••• • ••• • •••• , 

· · · · v~i~;"~· v~i;; i~.iV~·; -p;~~~;,~· · · ·1· 

1 

Dosage Scenarios 

Permeant 

fug/cm2l 

0.0872 

Immobile 

Vehicle 

fmg/cm2l 

0.0 

4.994E-11 

0.091 

Removal Timeline Scenario 

fhoursl 

0.0 0 

Page 25 of 31 

[torr]) 32°C 
Total Applied 8.72£-02 )lg/cm2 

Description ofDosa2e Scenarios 

1 

1 At time zero 0.0872 )lg/Cm2 of permeant was applied to the skin . 

Maximum Fluxes and Concentrations 

Maximum Absorptive Flux (max(Jabs)) 

Time to Max Abs Flux 

Maximum Evaporative Flux 

Time to Max Trap Flux 

Max Mid-Epidermal 

Concentration (Cmax) 

2.693£-11 

I 8.000 

1 9.662£-05 

2.778£-10 

2. 11 2£-07 

)lg cm-2 h-1 

hours 

)lg cm-2 h- 1 

hours 

)lg/cm3 

Max Mid-Epidermal 

Free Concentration (Crrcc) 

4.210£-09 )lg/cm3 

Time to Max Mid-Epidermal 

Concentration tTmn~) 

Diffusive Resistance 

8.000 hours 

Skin Layer Diffusive Resistance [em/b) Control 

Stratum Corneum 1956.541 98.93 % 

Viable Epidermis 2.028 0.10 % 

Dermis 19.113 0.97% 

........................... Total 1977.682 100.00% 

Effective kp {ctn/11/ 5.056£-0-1 

General Simulation Parameters 

Time Above Set Concentration 1 8.oo hours 

Max Simulation Duration 8.00 hours 

Simulation Time 8.00 hours 

Page 26 of 31 

3.004£-07 !lM 

5.987£-09 !lM 
Results 

Calculated Permeant Distribution 

Removed 

Evaporated 

l .. ~?.~~~~ ...................... .. Stratum Corneum ..................................... 1 Viable Epidermis 

Dermis 

Total 

T imeStamp : 

Time: 20 16/02/23 15:39:39 

Actual imulation Time : 7.136E-03 seconds 

0.0 % 0.0 g/ 2 

0.89 % 7.730£-04 g/cm2 

20.92 % 

78.96 % 

0.0 18 ~g/c 2 

0.069 flg/cm2 

2.49E-06 % 2.173£-09 2 

2.57E-06% 2.244£-09 flg/cm2 

100.76 % 0.087 g/cm2 

Tahle. Plot. and Output Preparation Time: 0.013 seconds Total Simulation 

Time : 0.020 seconds 

ystem Memory Used :34M B JVM version 

: 1.8.0_5 1 

Program Version : f_4c31java_vi.O 

Method Version : 4C3L version 2.4._09.09.2010 rev 3.0 

Page 27 of 31 
Attachment 4 

Table A.4.1. Summary of Toxicological Doses and Endpoints for Bromodiolone for Use in Occupational 

Human Health Risk Assessment" 

Uncertainty/ RID, PAD, 

Level of Exposure/ Point of FQPA Concern for Study and Toxicological Effects Scenario Departure Safety Risk Factors Assessment 

Dennal Prenatal Developmental Toxicity Study in Rabbit Short-Tenn 

(1-30 days) UFA= IOX Residential LOAEL = 8 ).lg/kg/day, based on vaginal bleeding in 

NOAEL = dams. and 4).1glkglday UFH = lOX LOC for 

Intermediate MOE = 100 

Term (I - 6 A dermal absorption factor of I 0% is assumed for 

months risk assessment purposes 

Inhalation Prenatal Developmental Toxicity Study in Rabbit Short-Tenn 

(1 -30 days) UFA= lOX Residential LOAEL = 8 ).lg/kg/day, based on vaginal bleeding in 

NOAEL = UFH = lOX dams. and 4).1g/kg/day UFos=fX LOC for 

Intermediate MOE = 100 

Tenn(I-6 Toxicity via the dennal route assumed equivalent to 

months 

oral in the absence of inhalation toxicity data. 

Cancer (oral, 

dennal, Classification: None. Carcinogenicity studies not required for non-food use. 

inhalation) 

a Pomt of Departure (POD) = A data pomt or an estimated pomt that IS dcnvcd from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. 

OAEL = no observed adverse eRect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspccics UFon = database uncertainty factor: usc of a short-term study for intcm1cdiatc-tcrm risk assessment.. 

LOC = level or concern. 

Page 28 of31 
Attachment 5 

Acute Toxicity 

Table A.S.l. Acute Toxicity Profile for Bromadiolone 

Guideline Study Results Category 

870.1100 Oral Acute LDso Rat Between 0.56 and 0.84 mg!kg I 

870.1200 Dermal Acute LDso Rabbit 1.7lmglkg I 

870.1300 Inhalation Acute LDso Rat 0.43 mg!kg I 

870.2400 Acute Eye Irritation Rabbit Irritation. cleared by 4 days Ill 

870.2500 Acute Dermal Irritation Rabbit Minimally irritating IV 

870.2600 Dermal Sensitization No data available 

Non-Acute Toxicity 

Table A.S.2. Repeated Dose Toxicity Profile of Bromadiolone 

Guideline Study, Species MRID (Year), Dose Results 

Levels, Classification 

870.3050 20-day oral gavage, rat 00 I 07035 ( 1992) NOAEL < 6.4 ~glkg bw/day, not established 

0, 6.4, 12.4, 24.8 LOAEL = 6.4 ~tg/kg/day based on 

~g/kg bw/day hemorrhage in orbital sinus, nasal cavity and 

nail bed; anorexia and polydypsia; internal 

Core Supplementary bleeding and hemorrhagic spots on liver, Gl 

(non-guideline) and kidneys. 

870.3150 90-day oral capsule, dog 92 1960 13 ( 1992) NOAEL = I 0 ~glkg bw/day 

0,5, 10, 15,25.50. 100 LOAEL = 15 ~g!kglday based on increased 

J.lg/kg bw/day prothrombin time and hematuria. 

Core Supplementary At higher doses. internal hemorrhage, 

(non-guideline) congestion and/or edema of spleen, kidneys, 

lungs, urinary bladder, small intestine, liver, 

thyroid, skin were observed 

870.3700a Developmental Toxicity, 92 1960 14 ( 1992) Maternal 

rat 0, 17 .5, 35, 70 1-lg/kg/day NOAEL = 35 J.lg/kg bw/day 

LOAEL = 70 11glkg/day based on vaginal 

Acceptable/Guide I inc bleeding, hypotonicity, pale eyes 

Developmental 

OAEL = 70 11glkg bw/day 

LOAEL = not established 

870.3700b Developmental Toxicity, 92196015 ( 1992) Maternal 

rabbit 0, 2, 4, 8 !lglkg!day NOAEL = 4 ~g!kg bw/day 

LOAEL = 8 J.lg/kg/day based on vaginal 

Acceptable/Guideline bleeding 

Developmental 

NOAEL = 8 11glkg bw/day 

LOAEL = not established 

Page 29 of 31 
Table A.S.2. Repeated Dose Toxicity Profile of Bromadiolone 

Guideline Study, Species MRID (Year), Dose Results 

Levels, Classification 

870.5 100 In vitro Bacterial Gene 42632 10 I ( 1992) Negative. 

Mutation 0, 3.33- 1000 J.lg/plate, There was no evidence of induced mutant 

without S9-mix colonies over background. 

Acceptable/Guideline 

870.5375 In vitro Mammalian 42943503 ( 1992) Negative. 

Cytogenetics 0, 4.49, 9.99, 25.0. 50.0, There was no evidence of chromosome 

Chromosome Aberration 74.9, 99.9 jlg/mL aberrations induced over background, even 

Assay without S9; in the presence of cytotoxicity at 74.9 ug/ml 

0, 37.5, 50.0, 74.9. 99.9 or above. 

J.!g/mL in the presence of 

S9 activation 

Acceptable/Guideline 

870.5395 In vivo Mammalian 42943504 ( 1992) Negative. 

Cytogenetics- No evidence of toxicity in harvested bone 

Erythrocyte 400 jlg/kg marrow cells, even though death occurred in 

Micronucleus assay in some treated males and females. 

the mouse 

Acceptable/.e,uideline 

870.7485 Absorption Distribution 4259680 I ( 1992) Liver concentrations were measured on day 

Metabolism Excretion one and day 200 post dosing. 

0.2 11glkg bw as a single 

dose. T 112 in I iver = 17 days in phase I of a biexponential pattern, and 3 18 days for phase 

Acceptable/Guideline 2, indicating a substantial retention of 

bromadiolone in the liver for a long time. 

Page 30 of 31 
Attachment 6 

The requirements ( 40 CFR § 158.340) for the non-food uses for bromadiolone are in Table A.6. 

Use of the new guideline numbers does not imply that the new ( 1998) guideline protocols were 

used. 

Table A.6. Toxicology Da ta Req uirements 

G uideline Study Type Required Submitted Satisfi ed 

870.1 100 Acute Oral Toxicity y y y 

870.1200 Acute Dermal Toxicity y y y 

870.1300 Acute Inhalation Toxicity y y y 

870.2400 Acute Eye Irritation y y y 

870.2500 Acute Dermal Irritation y y y 

870.2600 Skin Sensitization y N N 

870.3 100 90-Day Oral Toxicity in Rodents y y y 

870.3150 90-Day Oral Toxicity in Non-Rodents y y y 

870.3200 2 1/28-Day Dem1al Toxicity y N N 

870.3250 90-Day Dermal Tox icity N N -- 870.3465 90-Day Inhalation Toxicity y N N 

870.3700 

Prenatal Developmental Toxicity Study (Rat) y y y 

Prenatal Developmental Toxicity Study (Rabbit) y y y 

870.3800 Reproduction and Fenility Effects y N Waived3 

870.4100 Chronic Toxicity (Rodent} N N --

870.4200 Carcinogenicity (Rat) N N -- Carcino~cnicity (Mouse) N N -- 870.5 100 Bacterial Reverse Mutation Test y y y 

870.5300 in vitro Mammalian Cell Gene Mutation Tcstl y y y 

870.5375 in 1·itro Mammalian Chromosome Aberration Test 

870.5385 Mammalian Bone Marrow Chromosomal Aberration Tcst2 y y y 

870.5395 Mammalian Ervthrocvte Micronucleus Test 

870.6100 Delayed Ncurotoxicitv of Organophosphorus Substances (Acute. lien) CR N -- Delayed Neurotoxicity o f Organophosphorus Substances (28-Day. lien} N N -- 870.6200 Neurotoxic ity Screening Banery (Acute. Rat) y N Waived3 

Neurotoxicity ScreeningBattery (90-Day. Rat) y N Waived3 

870.6300 Developmental Neurotoxicity Study CR N -- 870.7200 Companion Animal Safety N N -- 870.7485 Mctabol ism and Pharmacokinetics y y y 

870.7600 Dermal Penetration N N -- 870.7800 lrnmunotoxicity y N Waived3 

.. CR = Condr11onally eq t~~red 

2 Either guideline study type may be used to satisfy the data requirement (e.g .. 870.5300 or 870.5375) 

3 Study not expected to provide a lower point of depanure (POD) for risk assessment 

Page 31 of 31