### UNITED STATES ENVIRONMENTAL PROTECT I ON AGENCY
W ASHIN G T O N

. D

. C

. 20 4 60

March 9, 2016



### M EM ORAND U M OFFICE OF CH EM ICAL SAFETY AND PO L LUTIO N PREVE N TION



### P C C ode 128967 DP Barcode 429400

SU B JEC T : Prob l em Formulation for R egistration Rev i ew of Difethialone



### F RO M :

REV I EWE D 

### B Y : Justin Housenger
, Biologist Gabriel Rothman , E nvironmental Scientist Environmental Risk Branch V Environmental Fate and Effects Division (7507P) 

# .3// 0 / / 

# 0

THR OUG H: Mah 

### T. Shamim, Ph.D

.. Branch Chief

# ;/~-"v - Environmental Risk Branch V Env i ro n me n ta l Fate and Effects Division (7507P)



### TO : Ricardo Jones
, Chemical Review Manager Melissa Grable, Team Leader Neil Anderson, Branch Chief Ri sk Management and Implementation Branch 

### I
Pe st icide Re-Evaluation Di v ision (7508 P )

Pl ease. find attached the Preliminar y Problem Formulation for the Ecological Risk Assessment and Drinking Water Exposure Assessment for Re gist r at ion Review to be conducted for Difethialone.

### 2 

# Problem Formulation for the Environmental Fate, Ecological Risk , Endangered Species, and Drinking Water Exposure Assessment s in Suppor t of the Registration Review for Difethialone

Difethialone CAS No. 104653

- 34

- 1 PC Code 128967

Prepared by: Brian Montague

, Fishery Biologist José Meléndez , Chemist U. S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch V 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 Reviewed by: Justin Housenger, Biologist Gabriel Rothman, Environmental Scientist Mah Shamim, Ph.D. , Chief ERB5

### 3 

# Contents
1.0 Executive Summary

................................ ................................ ................................ ............. 4 2.0 Introduction

................................ ................................ ................................ .......................... 5 3.0 Use Char acterization

................................ ................................ ................................ ............ 6 4.0 Conclusions from Previous Risk Assessments

................................ ................................ .... 7 4.1 Ecological Risk Assessment

................................ ................................ ............................. 7 4.2 Drinking Water Exposure Assessments

................................ ................................ ........... 8 4.3 Clean Water Act Programs

................................ ................................ ............................... 8 5.0 Environmental Fate and Transport

................................ ................................ ....................... 9 5.1 Transformation Products

................................ ................................ ................................ 12 6.0 Receptors

................................ ................................ ................................ ............................ 13 6.1 Toxicity S ummary

................................ ................................ ................................ .......... 13 6.1.1 Effects to Aquatic Organisms

................................ ................................ ................. 13 6.1.2 Effects to Terrestrial Organisms

................................ ................................ ............. 14 6.2 Ecological Incidents

................................ ................................ ................................ ....... 15 7.0 Exposure Pathways of Concern

................................ ................................ ......................... 16 7.1 Aquatic Exposure

................................ ................................ ................................ ........... 16 7.2 Terrestrial Exposure

................................ ................................ ................................ ....... 17 8.0 Analysis Plan

................................ ................................ ................................ .......................... 17 8.1 Stressors of Concern

................................ ................................ ................................ ....... 17 8.1. 1 Ecological Risk Assessment

................................ ................................ ................... 17 8.1.2 Drinking Water

................................ ................................ ................................ ......... 17 8.2 Measures of Exposure

................................ ................................ ................................ .... 18 8.2.1 Estimating Primary Terrestrial Exposure

................................ ................................ 18 8.2.2 Accumulation Through Multiple Feedings on Bait

................................ ................ 19 8.2.3 Estimating Secondary Terrestrial Exposure

................................ ............................ 19 8.2.4 Estimating Aquatic Exposure

................................ ................................ ................. 20 8.2.5 Available Water Monitoring Data

................................ ................................ .......... 20 8.3 Measures of Effect

................................ ................................ ................................ ......... 20 9.0 Endangered Species Assessments

................................ ................................ ........................... 21 10.0 Endocrine Disruptor Screening Program

................................ ................................ .............. 21 11.0 Preliminary Identification of Data Gaps

................................ ................................ ............... 22 11.1 Environmental Fate

................................ ................................ ................................ ..... 22 11.2 Effects

................................ ................................ ................................ ......................... 23 12.0 References

................................ ................................ ................................ ............................. 26 Appendix A. Bibliography of Studies Submitted to EPA

................................ ............................. 28 Appendix B. EPI Suite v.4.11 Output File for Difethialone

................................ ........................ 31 Appendix C. SIPS Model Input/Output Summary

................................ ................................ ....... 45

### 4 

# 1.0 Executive Summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of difet hialone, a coumarin second generation anticoagulant rodenticide (SGAR), for control of Norway rats, roof rats and house mice , among a few other rodents

. It appears that the primary route of transport for difethialone to terrestrial organisms is consumptio n of bait product and movement of the in gested chemical within the bodies of the vertebrates or invertebrates that feed on the bait and move to offsite locations. Difethialone may require a period of days before it kills birds, mammals, or other organisms which feed on the bait. These poisoned animals may in turn become sources of exposure to difethialone if consumed by other predators, scavengers, or insectivores or if the predators feed poisoned animals to their own young . Relevant exposure pathways wi ll be the primary focus of the Difethialone Preliminary Risk Assessment (PRA).

The problem formulation describes the methods planned for use during the completion of drinking water and ecological risk assessments in support of registration review and prov ides an overview of the environmental fate, ecological effects, and potential risks associated with the use of difethialone as well as uncertainties unique to risk assessment of difethialone . This document also identifies additional studies that would be beneficial to the conduct of an ecological risk
assessment. Key uncertainties and related data requirements are listed below:

Environmental Fate Uncertainties and Data Requirements Certain environmental fate studies were submitted and considered suitable for a deterministic risk assessment. Quantitative structure activity relationships (QSARs) ( e.g. , EPI Suite v.4.1 ) were used to determine some of the environmental fate properties of difethialone

. Data have not bee n submitted to fulfill some conventional environmental fate studies; however, these data are not necessary fo r risk assessment at this time.

It appears that there is a low potential for residues of difethialone to leach (or be extracted) from the bait sta tions , if exposed to normal rainwater or runoff , and to reach surface water

. There is o ne possible exception : the use of the chemical in sewers systems. The concern s for sewer use are that

non

- target organisms may visit sewers and /or chunks of bait block s could be knocked or broken off as bait is eaten, discharged with stormwater or sewage overflow, and then c onsumed by non

target organisms . For the uses on sewer systems, instructions indicate to thread wire through blocks and securely attach to a statio nary structure such as the bottom step of a manhole ladder or a sewer grate, allowing just enough wire for the block to rest on manhole benching. If benching is not present, blocks should be suspended a few inches above the high water mark, thus preventin g removal by rats or water. EFED recommends confirmation that suitable instructions are included in the labels, to limit exposure of difethialone to sewer water, or to non

- target organisms in sewer systems.

### 5 Ecological Effects Uncertainties and Data Req uirements For ecological effects there have been no studies submitted to characterize chronic toxicity to avian species ( i.e. , avian reproduction studies). An acute contact toxicity study with the honey bee is not available for this assessment. There are no studies to characterize chronic effects to aquatic organisms or acute effects to aquatic plants. For current uses only avian studies are being requested. Significant exposure to aquatic organisms and honeybees is not expected from current labeled us es.

850.2100 Acute Oral Toxicity

– Passerine Species Smaller p asserine species may be more sensitive than species previously tested with difethialone. Currently no data is available to clarify this uncertainty.

850.2300 : Avian Reproduction Study : Litt le is known about the effects of low level sub

lethal dietary levels on reproductive success for non

- target avian species. Difethialone is shown to accumulate in adult tissues and blood of birds who have presumably ingested contaminated prey, but not succ umbed to these exposure levels. Due to the extreme acute toxicity of this chemical to birds a design protocol should be submitted before conduct of the studies for determination of test concentrations and methods. This guideline testing is requested for o ne upland game species and one waterfowl species.



# 2.0 Introduction

Difethialone is a coumarin second generation anticoagulant rodenticide (SGAR), for control of Norway rats ( Rattus norvegicus) , roof rats ( Rattus rattus ) and house mice ( Mus musculus ) 1



### . According to the 2004 Comparative Assessment (USEPA 2004b), the anticoagulant rodenticides’ mode of action is as follows: “The anticoagulant rodenticides are vitamin

- K antagonists that disrupt normal blood

- clotting mechanisms and induce capillary damage ( Pelfrene 1991). Death results from hemorrhage, and exposed animals may exhibit increasing weakness prior to death. Behavior also may be affected (Cox and Smith 1992)

.

S 

### econd

- generation anticoagulants tend to be more acutely toxic than are the first

generation anticoagulants, and they are retained longer in body tissues of primary consumers. The greater potency and duration of action of long

- acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)

- 2,3

- epoxi de reductase; (ii) ability to disrupt the vitamin K(1)

- epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half

- lives due to high lipid solubility and enterohepatic circulation (Watt et al. 2005).

In genera l, rodents require only one feeding of bait to receive a lethal dose. Because it takes several days for the rodent to die, animals may return to feed on the bait, thus acquiring multiple doses and allowing for higher, more lethal concentrations of the rode nticide to accumulate. Second generation anticoagulant rodenticides become concentrated in the animal’s liver, with liver half

- lives of up to a year. If an animal that consumes a second generation anticoagulant rodenticide is eaten by a predator or scave nger , the animal can then become secondarily exposed and affected by the

1 Further, difethialone may also be used to control deer mice, and white footed mice in and within 100 feet of

agricultural or man

- made structures.

### 6 rodenticide. Because of their long half

- lives, these rodenticides have been shown to bioaccumulate in

non

- target wildlife

. 

### EFED evaluated the most recent ecological risk assessments for difethialone to update the toxicity, exposure, and usage information and determine if sufficient data are available or whether further updates are needed to support registration review. Previous risk assessment s include the Reregistration Eligibility Decision (RED): Rodenticide Cluster that was published in July 1998 (USEPA, 1998b), the 2004 document Potential Risks of Nine Rodenticides to Birds and Nontarget Mammals: a Comparative Approach (USEPA 2004b), and a 201 1 endangered species asses sment for th e Alameda whipsnake, salt marsh harvest mouse, and San Joaquin kit fox (USEPA 201 1b ). In 2011 there was a Scientific Advisory Panel (SAP) and Notice of Intent to Cancel (NOIC) Non

Compliant Rodenticides

. In June of 2013 the California Department of Pestic ide Regulation issued an extensive analysis of second generation rodenticide use in California entitled Second Generation Anticoagulant Rodenticide Assessment which also provides valuable information on effects of actual use of difethialone and other similar rodenticide products in that state

. In addition, EFED considered the latest Agency science policies and risk assessment methodologies. The structure of d ifethialone, as well as the chemical names and other identifiers can be found in the Figure 1 and the chemical identity table ( Table 2 ).



# 3.0 Use Characterization

Current uses of difethialone have been established consistent with a Risk Mitigation Decision (RMD) in 2008 encompassing ten rodenticides. The RMD includes two important provisions that relate to difethialone. First, for all second generation anticoagula nts (the subclass of rodenticides to which difethialone belongs), application is restricted to tamper resistant bait boxes for all above ground uses. Second, package size restrictions on these second generation anticoagulants prevent the average consumer ( e.g. homeowners) from purchasing any package size less than 16 lbs . Prior to the RMD, consumers (particularly homeowners looking for readily accessible rodent control options) were able to purchase difethialone

- containing products in small packaging in g rocery stores, warehouses and many other commercial establishments. It was anticipated that the movement of second generation rodenticides such as difethialone to tamper resistant bait boxes would reduce primary exposure to non

- target organisms, but that the potential for secondary exposure would still exist since difethialone is very acutely toxic to birds and mammals and has a long persistence in body tissues, making it available to secondary consumers ( e.g

. predatory birds).

Current Office of Pesticide Programs (OPP) use information lists 14 registered active end

use products

. One registrant produces the technical grade active, Liphotech, Inc (98% ai). See Appendix D for a complete listing of registered products

. Formulation types registered include pellets, blocks, mini blocks, meal, and paste (all formulations are bait/solid). Rodent control baits containing difethialone are registered for use in and around agricultural and commercial buildings, households/domestic dwellings (indoor and outdoor pre mises), commercial transport facilities and vehicles, refuse solid waste containers (garbage cans), ships and boats , and in sewers. For outdoor application s , rodent control bait containing difethialone must be placed within 100 feet of
structures. Produc t l abels for difethialone do not limit the amount of product or active ingredient

### 7 that may be applied per unit area, the number of applications that can be made per unit time, or the minim um i nterval between applications. Instead, l abels state the amount of bait that may be placed in one location, and the linear distance between placements. The linear distance is 15 to 30 feet

. The concentration of difethialone in the bait is 0.0025% for all of its products ( i.e. 25 mg a.i./kg bait ) . The amount of activ e ingredient per placement, or the amount of active ingredient per linear f

ee t, can be calculated for the products (usually ~1 lb bait per placement or 0.000025 lb a.i. per placement or per manhole)

. Burrow baiting is prohibited for difethialone products.

The chemical profile produced by the Biological and Economic Analysis Division (BEAD) , located in the docket, lists the use patterns of maximum exposures for the current uses of difethialone. EFED will use application scenarios that result in maximum exposure for a given use for the risk assessment. Any absence of information on the labels that specifies the maximum application scenario, the application interval, the annual maximum number of applications allowed, or application method may result in co nservative assumptions.



# 4.0 Conclusions from Previous Risk Assessments

**4.1 Ecological Risk Assessment** 

The Agency has conducted multiple ecological risk assessments on difethialone that serve

as a b asis for this scoping document. A n assessment of the risks of difethialone to terrestrial wildlife was included in the 2004 document Potential Risks of Nine Rodenticides to Birds and Nontarget Mammals: a Comparative Approach (USEPA 2004b). In 201 1 an endangered species
assessment was con ducted regarding the use of difethialone and the federally threatened Alameda whipsnake (AW, Masticophis lateralis euryxanthus ), the federally endangered salt marsh harvest mouse (SMHM, Reithrodontomys raviventris ), and the federally endangered San Joaquin kit fox (SJKF, Vulpes macrotis mutica ) (USEPA 201 1b) and examined the potential for exposure of these species and taxa to difethialone use in California.

In 2008, EPA released the Risk Mitigation Decision for Ten Rodenticides (RMD) (EPA 2008, Docket ID EPA

- HQ

- OPP

- 2006

- 0955 ). Difethialone products were included in the list of ten rodenticides addressed in this document. The focus of this decision was:

1) T o minimize children’s exposure to rodenticide products used in homes by requiring that all rodenticide bait products marketed to general and residential consumers be sold only with bait stations, with loose bait ( e.g. , pellets and meal) as a prohibited bait form. 2) To reduce wildlife exposures and ecological risks, by requiring sale and distribution limits i ntended to prevent general consumers from purchasing residential use bait products containing four of the ten rodenticides that pose the greatest risk to wildlife (the second generation anticoagulants

– brodifacoum, bromadiolone, difenacoum, and difethialo ne). Moreover, bait stations will be required for all outdoor, above

- ground uses of these second generation anticoagulants.

For brodifacoum and difethialone, certain labels were not brought into compliance with these provisions of the RMD. Consequently, these second generation anticoagulant rodenticides

### 8 were, along with warfarin and bromethalin, the subject of a Notice of Intent to Cancel (NOIC) hearing. In the case of bromethalin, there were both RMD

- compliant and non

- compliant labels. Additionally, tw o first generation anticoagulant rodenticides that would serve as the likely alternatives with the removal of the chemicals concerned in the NOIC (chlorophacinone and diphacinone) were assessed. To support the NOIC, EPA conducted an extensive assessment of the potential for primary and secondary effects of the rodenticides under evaluation which updated previous risk assessment findings conducted in support of the May 2008 RMD through the application of additional effects and exposure data, use of additional exposure modeling, and quantitative risk assessment techniques

. This work was brought before the Science Advisory Panel (SAP) in 2011 for review; meeting materials are available under docket number EPA

- HQ

- OPP

2011

- 0718.

T he primary risk issues have been identified for c ertain terrestrial non

- target animals

, consistent with a rodenticide use . In the 2004 EPA Paper by Urban and Erickson the assessment stated: “ Brodifacoum and difethialone stand out as the two rodenticides posing the greatest
po tential overall risk to birds and non

- target mammals, followed by bromadiolone and diphacinone.” Also the paper states “Brodifacoum and difethialone pose the greatest potential risks to avian predators and scavengers that feed on target or non

- target anim als poisoned with bait.”

In t he most recent, comprehensive assessment conducted for difethialone

, the endangered species assessment (ESA, USEPA 2011b), th e major ecological conclusions for risk were as follows:

Table 1 . Summary of Risk Concerns Identifie d for Difethialone in Previous ESA

Birds Mammals Terr. Plants Terr. Inverts Fish BCF Aquatic Inverts Aquatic Plants Groundwater Contamination Persistence Degrades of Concern Yes Yes No 1 NA NA Yes 2 NA No 1 No Yes 2 None Yes = at least one LOC has been exceeded in previous assessments; “No” = LOCs have not been exceeded in previous assessments; NA = RQs have not been calculated previously.

1 E ffects on terrestrial and aquatic plant communities were judged to be discountable.

2 Al though there is no Fish BCF study for difethialone, open literature studies suggest that difethialone persists in liver tissue of terrestrial animals.



## 4.2 **Drinking Water Exposure Assessments**

A drinking water assessment has not been previously conducted o n difethialone. The exclusive use of difethialone bait outdoors in bait stations, the extremely low concentrations in bait, and the hydrophobicity of the compound

, reduces po tential for extraction (leaching) of difethialone residues f rom the bait station, or leaching to subsurfaces or runoff , if exposed to rainwater or runoff. Surface or groundwater exposure is expected to be negligible. Refer to Section 8. 1.2 for further details.



## 4.3 **Clean Water Act Programs**

Difethialone is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act , based on information provided at

### 9 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885



### . No Total Maximum Daily Load (TMDL) criteria have been developed for difethialone , based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES . Aqu atic benchmarks have been established for difethialone ( available at http://www.epa.gov/pesticide

- science

- and

- assessing

- pestic ide

risks/aquatic

- life

- benchmarks

- pesticide

- registration ) . Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks if applicable.



# 5.0 Environmental Fate and Transport

Table 2 lists the physic o chemical properties of difethialone

. Table 3 lists the other environmental fate properties of difethialone

, from the submitted environmental fate and transport studies

. The structure of difethialone is provided in Figure 1

.

Figure 1. Structure of Difethialone 2

2 The structure was obtained from the difethialone data sheet available a t the following site accessed 08/26/ 2015:

http://www.alanwood.net/pesticides/difethialone.html

.

### 10 Table 2. Physicochemical Properties of Difethialone Property Value and units MRID or Source Molecular Weight 539.495 g/mole N/A Chemical Formula C 31 H 23 BrO 2 S N/A

CAS Name 3

- [3

- (4′

- bromo[1,1′

- biphenyl]

- 4

- yl)

- 1,2,3,4

- tetrahydro

- 1

- naphthalenyl]

- 4

- hydroxy

- 2 H

- 1

- benzothiopyran

- 2

- one Difethialone data sheet

IUPAC Name 3

- [(1 RS ,3 RS ;1 RS ,3 SR )

- 3

- (4′

- bromobiphenyl

- 4

- yl)

- 1,2,3,4

- tetrahydro

- 1

- naphthyl]

- 4

- hydroxy

- 1

- benzothiin

- 2

- one where the ratios of the racemates (1 RS ,3 RS ) to (1 RS ,3 SR ) lie within the ranges 0

– 15 to 85

– 100 respectively Difethialone data sheet

Bulk Density 1.3614 g/cm 3 at 25 0 C MRID 42065002
Vapor Pressure 0.074 mPa = 5.55x10

- 7 mm Hg @ 25 o C ‘Non

- volatile from a field condition’ EPI Suite v.4.11 USEPA, 2008a

Henry’s Law Constant 1.00 x 10

- 6 atm

- m 3 /mole @ 25 o C EPI Suite v.4.11 calculated from WS and VP

Water Solubility 0.4 mg/L 0.39 mg/L @ 25 o C MRID 42065002 EPI Suite v.4.11 reported value Octanol

– water partition

coefficient ( log K OW ) 9.82 6.29 at pH 7.3 and RT EPI Suite v.4.11 Assessment Report 1 Dissociation Constant (pK a and/or pK b ) Not available Not available

Air

- water partition coefficient (K AW ) K AW = C air /C water = HLC/RT K AW = 4.09 x 10

- 5 ‘Slightly volatile from a water surface’ Calculated Value, USEPA, 2008 a

Octanol

- air partition

coefficient (K OA ) Constant Law s Henry' RT K
K K K OW

AW OW OA = =

K OA = 1.7 x 10 14 Calculated value, using K OW value from EPI Suite v.4.11
UV/visible light absorption Three maxima at 209, 239 and 261 nm ; Approximately 234

, 260 and 330 nm Reported in DER for MRID 40268902 ; Assessment Report 1

C water+soil /C air C water+soil /C air = (1/K AW ) (1/r + K d ) = 2.0 x 10 10 ‘Non

- volatile from moist soil’ Assuming K d ≈ K F Calculated value USEPA, 2008 a 1. Assessment Report published by the EU dated 06/21/2007 (r apporteur state Norway)

. 2. The structure of the chemical was obtained from the difethialone data sheet available a t http://www.a lanwood.net/pesticides/difethialone.html (accessed 0 8/26/2015 ).



### Table 3. Summary of Difethialone Environmental Fate Properties

Study Value and unit Degradates MRID or Source Study Classification

or Comment s

Abiotic Hydrolysis Half

- life = relatively stable; Reported to be 154

- 450 days, extrapolated at pH 5 , 7 and 9 None identified 40268902 Acceptable

Atmospheric Degradation Half

- life 1 = 0.183 days, hydroxyl radical reaction 0.084 days, for ozone reaction Not available EPI Suite v.4.11 Estimate N/A

### 11 Study Value and unit Degradates MRID or Source Study Classification

or Comment s

Direct Aqueous Photolysis Natural sunlight at RT Half

- life = 57.4 min, pH 5.0 61.5 min, pH 7.0 61.3 min, pH 9.0 It appeared that there was some degradation in the dark controls. At least two metabolites

were not identified, did not decrease in a 90 min

period 42785801 Cursorily reviewed

Aerobic Soil Metabolism Half

- life = 204 days, Sandy Loam; Unextracted residues appeared to increase with time, with up to ~35% at 9 months; No degradation in sterile samples after 181 days; Volatiles <1%. One was not identified and increased throughout the study 42785802 Cursorily reviewed

Freundlich solid

water distribution coefficient (K F ) K F , 1/n, soil texture (series) 7.7 x 10 5 , 1.89, MS c lay (Sharkey) 5.6 x 10 5 , 1.98, MD s and (Sassafras) 1.8 x 10 6 , 2.30, MD s andy c lay l oam (Sequatchie) 1.6 x 10 5 , 1.80, CA s andy l oam (Hesperia) Mean value = 8.2 x 10 5 N/A 42628109 Cursorily reviewed ; values presented in the table are shown

as reported in the study, very high 1/n values (>1.1) were observed Freundlich solid

water organic carbon normalized distribution coefficient (K F OC ) K FOC , 1/n, soil texture (series) 6.2 x 10 8 , 1.89, MS clay (Sharkey) 1.0 x 10 8 , 1.98, MD sand (Sassafras) 5.3 x 10 9 , 2.30, MD sandy clay loam (Sequatchie) 2.7 x 10 8 , 1.80, CA sandy loam (Hesperia) Mean value = 1.57 x 10 9

Bioconcentration Factor (BCF) Steady State BCF= log BCF = 2.74 (BCF = 555 L/Kg wet

- wt) Biotransformation t 1/2 = 4.66 x 10 3 d ays (normalized to 10 g fish) N/A EPI Suite v.4.11 Estimate N/A

Abbreviations: wt=weight; RT = room temperature

. 

### It appears that the primary route of dissipation/transport for difethialone, relative to the exposure pathways for terrestrial organisms, is through consumption of bait product and movement of the intact chemical with in the bodies of the vertebrates or invertebrates that feed on the bait and move to offsite locations. Difethialone may require a period of days before it kills birds, mammals, or other organisms which feed on the bait. These poisoned animals may in turn become sources of exposure to difethialone if consumed by predators, scavengers, or insectivores or fed by them to their own young. Difethialone (CAS Chemical Name 3

- [3

- (4′

- bromo[1,1′

- biphenyl]

- 4

- yl)

- 1,2,3,4

- tetrahydro

- 1

- naphthalenyl]

- 4

- hydroxy

- 2 H

- 1

- benzothiopyran

- 2

- one ) is a slightly soluble compound (solubility of 0.39 mg/L at 25 0 C) and non

- volatile (vapor pressure of 5.55 x 10

- 7 

### mmHg at 25 0 C; calculated Henry’s Law Constant of 1.00 x 10

- 6 

### atm

- m 3 

### /mole). The compound is relatively stable to hydro lysis (half

- lives of 154

- 211 days at pHs 5, 7 and 9); however, the UV/Vis spectrum of the compound has a peak within the visible region, which suggests photolysis by sunlight can be important. This is confirmed by an available aqueous photolysis study i n which

### 12 the half

- lives were nearly 1 hour at all three pHs tested (5, 7 and 9). In a sandy loam soil, difethialone degraded slowly (half

- life 204 days, with no further identification data about the major degradate, which appeared to increase throughout th e study). The compound was immobile in four soils tested. Based on its low vapor pressure and Henry’s Law Constant, and the very low levels of volatilization observed in the aerobic soil metabolism study, this compound should not volatilize readily. Fur thermore, the very short atmospheric half

- lives predicted by EPIWEB v.4.11 (both, for ozone and hydroxyl radical reactions <<1 day), would indicate that atmospheric transport is not likely. Based on an estimated log K OW 

### value of 9.82 (EPIWEB v.4.11 estima te), bioconcentration in fish is anticipated should water exposure occur. The low application rates of difethialone per placement and its very high tendency to be adsorbed to soils (mean K F 

### ≈ 8.2 x 10 5 

### ; mean K F OC 

### ≈ 1.6 x 10 9 ) 

### indicate a low likelihood of runoff towards adjacent surface waters except when carried by eroded sediment. The applications of difethialone as bait products will not cause the chemical to drift. No monitoring data has been found for this chemical. Rodenticide test substances are n ot typically considered in surface or groundwater monitoring studies.



## 5.1 **Transformation Products**

No information about possible degradates of difethialone could be derived from the available environmental fate s tudies. The only exception is that one deg radate was observed in the aerobic soil metabolism study but it was not identified. Difethialone is relatively persistent in studies performed to assess its half

- life in livers of animals. Thus, it remains intact for several months if taken at sublethal levels and it appears unlikely that major (≥10% AR) metabolites would be formed in animal tissues.

### 13 

# 6.0 Receptors

**6.1 Toxicity Summary** 

Difethialone is considered very highly toxic to the freshwater fish and invertebrate species

as tested in the available acute toxicity studies. There are no chronic data available for freshwater fish and invertebrates. Additionally, no acute or chronic t oxicity data are available for estuarine/marine organisms . Finally, there is no data available to characterize the toxicity of difethialone to aquatic plants.

Difethialone is classified as highly toxic to birds and non

- target mammals. In these studies sublethal effects included lethargy, subcutaneous hemorrhaging, weakness, bloody diarrhea or urine and reduced food consumption and body weight loss. In addition, secondary toxicity to carnivorous birds or non

- target mammals feeding on contaminated carcass es has been observed in both laboratory and semi

- field studies as well as in field use of this chemical. No acute data on toxicity to terrestrial insects or plants are available.

**6.1.1 Effects to Aquatic Organisms** 

Table 4. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for Difethialone

Taxonomic

Group Study Type (percent a.i) Species Toxicity Value Acute Toxicity Classificati

on Source (Classification)

Freshwater fish 1 Acute (99.5%) Rainbow Trout
, Oncorhynchus mykiss 96 Hr LC 50 = 51 (36

- 100) ug ai/L Very highly toxic 40268914 Acceptable

Chronic No data available

Freshwater invertebrates Acute (98.9%) Water Flea

, Daphnia magna 48 Hr EC 50 = 4.4 (3.0

- 5.0) ug ai/L Very highly toxic 40268914 Acceptable

Chronic Water Flea No data available

Estuarine/marin e fish Acute Sheepshead Minnow

, C yprinodon variegat u s No data available

Estuarine/marin

e invertebrates Acute Eastern Oyster

, Crassostrea virginica No data available

Acute Mysid shrimp Americamysis bahi a No data available

Aquatic plants and algae Vascular Duckweed ( Lemna gibba ) No data available

Non

- vascular Aquatic Algae (Multiple species) No data available

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

### 14 **6.1.2 Effects to Terrestrial Organisms** 

Table 5. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Difethialone

Taxonomic

Group Study Type (percent a.i) Species Toxicity Value (all units in

terms of measured

active ingredient) Acute Toxicity Classification Source (Classification)

B irds 1 Acute (96 % ai) Bobwhite quail

, Colinus virginianus 30 D LD 50 = 0.26 (0.17

- 4.0) mg ai/kg

- bw Very highly toxic 40696901 Acceptable

Sub

- acute dietary (96% ai) Bobwhite quail

, Colinus virginianus 30

- day LC 50 = 0.56 (0.16

- 1.9) mg a.i/kg

- diet Very highly toxic 40696902 Acceptable

Chronic Bobwhite quail or Mallard duck No data available

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50 = 0.55 mg/kg of bw 40268903/ 42687704

Acute Oral

Difethialone/ Fipronil TEP Laboratory rat ( Rattus norvegicus ) LD 50 = >5050 mg/kg

- bw 47303013

Chronic Laboratory rat ( Rattus norvegicus ) No data available

Insects Acute contact (Adult) Honey bee ( Apis mellifera ) No data available

Terrestrial plants Seedling Emergence /Vegetative Dicot (Multiple species) No data available

Monocot (Multiple species) No data available

1 Birds represent surrogates for terrestrial

- phase amphibians and reptiles.

### 15 **6.1.3 Secondary Poisoning Potential**

Several laboratory and field studies regarding acute effects from secondary poisoning through ingestion of contaminated carcasses or live prey have evaluated for wild mammal and birds. This secondary poisoning could occur to adult birds feeding on poisone d carcasses or live animals as well as to young nesting birds when fed poisoned animal carcasses. These indirect adverse effects will be discussed in more detail in the risk characterization of the subsequent Preliminary Risk Assessment. Citations for th ese studies as well as other studies related to exposure to and toxicity of difethialone are included in the Ecological Effects Bibliography at the end of this document.

Table 6. Summary of Secondary Toxicity Studies
Taxonomic

Group Study Type Surrogat e Species Toxicological Observations Source (Classification)

Birds 1 Non

- guideline with technical grade ai Black

- Billed Magpies, Pica pica Dietary

- fed on rodent carcasses 33 day LC 50 = 4.48 ppm 46656501 Supplemental

Barn Owl, Tyto alba Evaluation of Secondary Poisoning of Difethialone Saravanan, K. Kanakasabai, R. (2004)

- open lit

Mammals Non

- guideline with technical grade ai European Ferrets
, Mustela putoris furo Dietary

- fed rodent carcasses LC 50 = 97 ppm 46656501 Supplemental



### These laboratory studies demonstrate that ingestion of contaminated carcasses may lead to adverse effects to birds and mammals which may feed on them. In the field these poisoned animals may be captured as live prey and consumed by adults or fed by them to their young aft er capture.



## 6.2 **Ecological Incidents**

The E cological I ncident I nformation S ystem (EIIS) is an OPP database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and ma gnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure. The Avian Information Monitoring System (AIMS) is a database maintained by the American Bird Conservancy that contains publicly available data on reported avian incidents invo lving pesticides. Many of the incidents listed in this database are also in the EIIS. Numerous incident investigations have detected difethialone residues in liver tissues of necropsied birds and mammals which had no direct contact with the baits.

In a recent 2015 query of the EIIS system, over 80 wildlife incident reports were obtained for difethialone, primarily from California and New York where robust incident reporting systems are maintained. There are also incidents reported from Massachusetts, Nebraska, and in open literature summaries. The lack of nationwide reporting of incidents is more indicative of the lack of reporting systems and not necessarily a lack of incidents within those use locations as second generation rodenticides are used in all states for rodent control. In eighteen of the incidents (23%)

### 16 difethialone was considered as highly probable as the cause of death, usually indicated by chemical residue analysis of body tissues, and/or gross pathological obs ervations such as hemorrha ging. Seven incidents (9%) were categorized as probable 23 (29%) were classified as possible in difethialone being the cause of the wildlife loss reported in the incident. Other incidents indicate exposure to difethialone as well as other second generati on anticoagulants when analyses of liver tissues were conducted. In preparation for the SAP to support the NOIC, incidents reported up to 2012 were analyzed and summarized regarding the species involved and the certainty of the chemical exposure causing th e effects that were observed.

A total of 25 new incidents have been reported involving difethialone subsequent to the implementation of restricted use and bait box requirements imposed by the Agency. The incidents include mortality to Red

- tailed hawks, a Cooper’s hawk, Red fox and bla ck bear, all of which showed difethialone concentrations in the liver ranging from 10 to 861 ppb. Further review and analysis of these incidents as well as any additional reports will be compiled in the subsequent Preliminary Risk Assessment.



# 7.0 Exposure Pathways of Concern

For most conventional pesticides, p otential transport mechanisms typically include for example surface water runoff and/or spray drift. However, because the only use of difethialone is in bait for rodent control, no potential for spray drift exists, and exposure from volatilization is expected to be minimal considering its low vapor pressure and Henry’s Law Constant.



## 7.1 **Aquatic Exposure**

Because difethialone bait is applied in bait stations outdoors, little potential exists for residues of difethialone to leach from the station, if exposed to rainwater or runoff. Furthermore, due to the extremely low concentration of active ingredient in the bait (0.0025%), small amount applied per placement (0.000026 lb ai)

, and the hydrophobic nature of the compound (log K OW 

### = 6.29

- 9.82 ), leaching of dissolved difethialone from the bait station would be so small that the potential for contaminating surface water is expected to be limited . Similarl y, exposure of surface water via erosion of soils that sorb difethialone is also expected to be negligible.

One possible exception would be the use of the chemical in sewers systems. The concern for sewer use is, both in the sewer ( i.e. , non

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

- target organisms). However, for the uses on sewer s ystems, instructions indicate to thread wire through blocks and securely attach to a stationary structure such as the bottom step of a manhole ladder or a sewer grate, allowing just enough wire for the block to rest on manhole benching. If benching is not present, blocks should be suspended a few inches above the high water mark, thus preventing removal by rats or water.

### 17 

## 7.2 **Terrestrial Exposure**

The most likely route of transport from the bait boxes is within the bodies of animals which feed directly on the difethialone bait. Because these poisoned animals are not killed immediately, they may travel a significant distance before dying, thereby potentially exposing other animals away from the application site. This transport within targeted animals is the major route of exposure for terrestrial non

- target animals whose diets may include small mammals, birds, and reptiles, thus making them vulnerable to secondary exposure from consuming poisoned prey. This hypothesis is supported by numerous incidents i n which animals too large to enter the bait boxes are found to contain the residues in liver or other tissues upon post mortem examinations.

In addition, insects such as ants or cockroaches are sometimes attracted to the bait and may feed on it or transport it outside of the bait boxes where they , as well as the bait particles, may be consumed by insectivorous wildlife.

Use of difethialone in bait products to control rodent pests is not expected to result in significant exposure to terrestrial plants. Bait is generally placed by hand in specific bait stations around buildings. The products containing difethialone may not be broadcasted. Any exposure to terrestrial plants would be minor and limited to the area immediately around the bait placement.



# 8.0 Analysis Plan

**8.1 Stressors of Concern** 

**8.1.1 Ecological Risk Assessment** 

For this assessment difethialone is considered the stressor of ecological concern for terrestrial and aquatic organisms , though exposure to aquatic habitats may be limited. No information about possible degradates of difethialone could be derived from the available environmental fate s tudies. The only exception is that one degradate was observed in the aerobic soil metabolism study but it was not identified. Difethialone is relatively persistent in studies performed to assess its half

- life in livers of animals. Thus, it remains intact for several months if taken a t sublethal levels and it appears unlikely that major (≥10% AR) metabolites would be formed in animal tissues.

**8.1.2 Drinking Water** 

A s noted in Section 4 .2 , a drinking water assessment has not been previously conducted on difethialone

. Because difethialone bait may be used outdoors only in bait stations

, little po tential exists for residues of difethialone to leach from the bait station , if exposed to rainwater or runoff. However, due to the extremely low concentration of active ingredient in t he bait (0.0025%), small amount applied per placement (~0.000026 lb a.i./placement) , and the hydrophobic nature of the compound (log K OW 

### = 6.29 ), leaching of dissolved difethialone from the bait would be so small that the potential for contaminating surfac e or ground water is expected to be insignificant.

### 18 Similarly, exposure of surface water via erosion of soils that sorbed difethialone is also expected to be negligible. Therefore, a drinking water assessment for difethialone will not be required.



## 8.2 **Measures of Exposure**

E xposure assessment methods employed by the Agency for the rodenticides differs from that for most other pesticides . For a rodenticide, the bait itself is the potential food item of concern. Thus , the amount of active ingredient in the formulated bait is used as an estimated environmental concentration ( EEC )

. This information is used to estimate the amount of grain bait that birds and mammals of various sizes need to consume to obtain a dose expe cted to be lethal to 50% of the individuals in the population ( i.e. , LD 50 

### dose).

**8.2.1 Estimating Primary Terrestrial Exposure** 

For birds and mammals, the assessment is based on the maximum concentration of difethialone in bait products used for rodent control. The maximum concentration is 0.0025% for all its products ( i.e. 25 mg a.i./kg bait) for products used to control rats and mice. The maximum known amount of active ingredient per placement for any product is 0.000025 lb a.i. or 11.3 mg a.i. when it is used to control Norway rats or roof rats. For dietary

- based risk, the concentration of difethialone in the bait is compared directly to the toxicity endpoint from dietary toxicity studies ( i.e.
, 40

- day LC 50 

### studies for birds and 14

- day LC 50 

### studies for mammals due to delayed toxicity of difethialone). For dosed

- based risk, the difethialone concentration in bait has to first be converted to a daily ingestion rate. This is done using the allometric equations of as provided in USEPA’s Wildlife Exposure Factor Handbook ( USEPA, 1993 )

- see table below. Ingested doses of difethialone (mg a.i./kg

- BW) will be calculated for birds and m ammals of various assumed body weights. The doses calculated for birds could also be used for reptiles and terrestrial

- phase amphibians. This approach is consistent with other rodenticide risk assessments conducted by the Agency.

Table 7

. Direct Exposu re Formulas for Calculation of Daily Intake Based on Consumption of Bait from Bait Boxes Passeriform bird food intake (g, dry weight ): FI (g dry

- wt/day) = 0.398 * Wt(g) 0.850



### Rodent mammal food intake (g, dry weight ): FI (g dry

- wt/day) = 0.621 * Wt(g) 0.564



### Food intake (g, wet weight ): FI (g wet

- wt/day) = FI (g dry

- wt/day) / 0.90

Difethialone intake (mg a.i./kg

- bwt/day) = FI (g wet

- wt/day) * mg a.i./kg

- bait / Wt(g)

Where: Wt(g) = weight (in grams) of the bird or mammal consumer

mg a.i./kg

- bait = 25 mg ai/Kg is maximum labeled difethialone concentration in bait

### 19 **8.2.2 Accumulation Through Multiple Feedings on Bait** 

Available data on the retention times of difethialone in animal tissues was assessed by the Agency in the 2010 White Paper for the Science Advisory Panel (SAP) review. Due to the attractiveness of bait formulations within the bait boxes and the longer tim e to death from exposure to second generation rodenticides, smaller animals can be expected to revisit the bait stations more than once and thus could obtain higher residue levels than single feed calculations might predict. Given the long retention time within tissues these levels are expected to increase incrementally if target or non

- target animals return to feed multiple times before death occurs. This can have implications for secondary toxicity assuming continually increasing accumulation levels wit hin the potential prey of scavenging or predatory animals which feed on them. Accumulation of difethialone within the prey animal over time would be calculated using an elimination rate constant based on t he liver half

- lives t o approximate elimination.

**8.2.3 Estimating Secondary Terrestrial Exposure** 

Secondary exposure analysis (from consumption of contaminated individuals or carcasses) requires consideration of potential concentrations of residues in tissues of target and non

- target organisms that are c ommonly consumed by predators and scavengers, how long the residues might persist in body tissues, and the amount of prey that would normally be consumed in a given time period by the species of concern. Studies determining residue concentrations for non

- target animals fed rodenticides have been both submitted by registrants and are available in open literature. In addition, several wildlife incident reports include difethialone post mortem analysis of residues found in liver and other tissues. Given the long residence times of second generation rodenticides these incident related analyses may prove invaluable in validating such estimates if time from ingestions and sources for exposure can be confirmed.

From the suite of studies tabulated below, difethi alone exhibits a half

- life in the liver ranging from approximately 29

– 108 days in the liver and 2

– 39 days in the blood. Table 8 below displays study results for retention times in blood or liver tissue reviewed for difethialone. Further review of any additional data may be included in the registration review process.

### 20 Table 8. Retention of Difethialone in Blood and Liver (table extracted from 2010 White Paper)

Species Dose (mg a.i./kg) # doses Blood t 1/2 a (days) Liver retention a,b (days) Reference (MRID , if available )

Mouse 20 μg/mouse 1 38.9 28.5 (t 1/2 ) Vandenbroucke et al. 2008

Rat 0.5 0 1 2.3 108 (t 1/2 ) Belleville 1986 (42065010) Lechevin and Poche 1988

Rat 0.06 4 (at weekly intervals) NA 74 (t 1/2 ) Belleville 1991 (42065009)

a t 1/2 for plasma and liver is the elimination half

- life

b liver retention is expressed as either the time period for which residues persist or as the elimination half

- life

c cited in Eason et al. 2001



### 8.2. **4 Estimating Aquatic Exposure** 

Difethialone is restricted to use within tamper proof bait boxes. Additionally, as described in Section 7

, due to the extremely low concentration of active ingredient in the bait (0.0025%), small amount applied per placement, and the hydrophobic nature of the compound (log K OW 

### = 6.29

- 9.82 ), leaching of dissolved difethialone from the bait station would be so small that the potential for contaminating surface water is expected to be insignificant. Similarly, exposure of surface water via erosion of soils that sorb difethialone is also expected to be negligible. I t is noted that the formulations for the uses in sewers include only blocks and mini

- blocks and the instructions appear to minimize potential exposure to water. Because of this, the aquatic exposure route will not be further assessed.

**8.2.5 Available**  **Water Monitoring Data**

The Agency is not aware of monitoring conducted by federal and state agencies and this route of exposure will be considered in the assessment to the extent that data on difethialone are available. Water monitoring programs general ly monitor for conventional agricultural pesticides and typically do not include analysis for vertebrate control agents such as difethialone



## 8.3 **Measures of Effect**

Toxicity data presented in Section 3 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will also be consider ed. The open literature studies are identified using EPA’s ECOTOXicology database ( www. epa .gov/ ecotox / )

, which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and funct ional characteristics of the affected communities.

### 21 

# 9.0 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 outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to difethialone in connection with the development of its final registration review decision for difethialone

.

In No vember 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim App roaches 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 j oint Interim Approaches are contained in the November 1, 2013 white paper

, Interim Approaches for National

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

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches 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 difethialone does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted during registrati on review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of difethialone will describe the level of ESA analysis completed for this particular registration review case. Thi s 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 imple mented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of difethialone as part of completing this registration review.



# 10.0 Endocrine Disruptor Screening Program

Difethialone was not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing or the second list of 109 chemicals proposed for future testing . For additional information the EDSP pro gram, visit http://www2.epa.gov/endocrine

- disruption

.

### 22 

# 11.0 Preliminary Identification of Data Gaps

**11.1 Environmental**  **Fate**

Table 6 id entifies environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment.

Table 6 . Submitted Environmental Fate Data for Difethialone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Are data needed to conduct risk assessment? Justification and Assumptions EPA will Make in Absence of Data

835.2120 Hydrolysis 40268902 Acceptable No

-- 1
835.2240 Aqueous photolysis 42785801 In review No

-- 1

835.2410 Soil photolysis None Not applicable No

-- 1
835.4100 Aerobic soil metabolism 42785802 In review No

-- 1

835.4200 Anaerobic soil metabolism None Not applicable No

-- 1

835.4300 Aerobic aquatic metabolism None Not applicable No

-- 1

835.4400 Anaerobic aquatic metabolism None Not applicable No

-- 1

835.1230 835.1240 Adsorption/ desorption and leaching 42628109 In review No

-- 1

835.1410 Volatility

– laboratory None Not applicable No

-- 1

835.6100 Terrestrial field dissipation None Not applicable No

-- 1

835.6200 Aquatic field dissipation None Not applicable No

-- 1

850.1730 Fish bioconcentration None Not applicable No

-- 1

850.6100 Analytical method in water None Not applicable No

-- 2

Analytical method in soil None Not applicable No

1. Data have not been submitted to fulfill some guidelines. Data gaps were not identified as these data are not necessary for risk assessment at this time. 2. Studies are not recommended at this time because terrestrial exposure estimates are assumed to be either non

degraded bai t, measured residues in tissues of animals that ingested difethialone, or estimated residues in tissues of animals that ingested difethialone. In the case of estimated residues, half

- lives in liver will be used to account for degradation.

### 23 

## 11.2 **Effects**

Table 7 and Table 8 identify ecological effec ts studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. Rationale for the additional data requested is presented below.

850.2100 A cute Oral Toxicity

– Passerine Species Smaller p asserine species may be more sensitive than species previously tested with difethialone. Currently no data is available to clarify this uncertainty.

850.2300 : Avian Reproduction Study : Little is known about the effects of low level sub

lethal dietary levels on reproductive success for non

- target avian species. Difethialone is shown to accumulate in adult tissues and blood of birds who have presumably ingested contaminated prey, but not succumbed to the se exposure levels. Due to the extreme acute toxicity of this chemical to birds a design protocol should be submitted before conduct of the studies for determination of test concentrations and methods. This guideline testing is requested for one upland ga me species and one waterfowl species.

850.1300 Chronic Lifecycle testing with Freshwater Invertebrate 850.1400 Early Lifestage Toxicity with Fish Difethialone displays very high acute toxicity to freshwater invertebrate and fish species. Chronic studies with fish and invertebrate species are usually required for all non

- residential outdoor uses. Use in stormwater pipes or sewer system drains could potentially lead to exposure to aquatic habitats. However, for the se uses , instructions indicate w ire should be inserted through blocks and securely attach ed to a stationary structure above high water levels

, thus reducing exposure potential

. In addition, the hydrophobicity of the compound, precludes potential for residues of difethialone to be leach ed fr om the bait station if exposed to rainwater or runoff. Surface or groundwater exposure is expected to be negligible. Though lack of chronic data is an uncertainty for future assessments these studies are not requested at this time , as exposure potential is low for current labeled uses.

850.3020 : Acute Contact Toxicity to Honeybees 850.3030: Honeybee residues on Foliage Special Study : Honeybee oral toxicity study Special Study: Honeybee adult and Larval Chronic toxicity These studies are g enerally requir ed of most outdoor use pesticides to which honeybees may be exposed or to which hives may be exposed through transport back to the colony. Due to uses restricted to bait boxes, exposure to honeybees is generally not expected for second generation rodentic ides such as difethialone. In addition, the current uses of difethialone are restricted to use near agricultural or industrial buildings, structures within commercial shipping areas such as docks or warehouses, or in transport vehicles such as rail cars o r ships. Based on limited exposure potential , no honeybee studies will be required at this time.

### 24 Table 7 . Submitted Aquatic Ecological Effects Data for Difethialone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed to conduct

risk assessment ? Jus tification and Assumptions EPA W ill Make in Absence of Data

850.1010 Freshwater invertebrate acute toxicity 40268914 with Daphnia magna Acceptable No Current data adequate to characterize toxicity for risk assessment purposes for
current uses
850.1025 850.1035 850.1045 850.1055 Saltwater invertebrate acute toxicity No data available No Data is not needed for current uses as aquatic exposure potential is limited and will not be assessed

850.1075 Freshwater fish acute toxicity 40268914 Rainbow trout Acceptable No Current data adequate to characterize toxicity for risk assessment purposes for
current uses 40268914 Bluegill sunfish Acceptable

850.1075 Saltwater fish acute toxicity No data available No Data is not needed for current uses as aquatic exposure potential is limited and will not be assessed 850.1300 Freshwater invertebrate life cycle No data available No

850.1350 Saltwater invertebrates life cycle No data available No

850.1400 Freshwater fish early

- life stage No data available No

850.1400 Saltwater fish early

- life stage No data available No

850.1500 Fish life cycle No data available No

850.4400 Aquatic plant Toxicity Test using Lemna spp. No data available No

850.4500 Algal toxicity No data available No

850.4550 Cyanobacteria No data available No



### Table 8 . Submitted Terrestrial Ecological Effects Data for Difethialone

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed for risk assessment ? Jus tification and Assumptions EPA will Make in Absence of Data

850.2100 Avian oral toxicity 40696901/42065004 Bobwhite quail Acceptable

### 25 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed for risk assessment ? Jus tification and Assumptions EPA will Make in Absence of Data

40268913/42687702 Japanese quail Supplemental Yes

- for passerine species only These data are partially adequate for risk assessment of currently registered uses

Risk to smaller passerine species cannot be estimated and sensitivity of this group may be higher than previously tested species

850.2200 Avian dietary toxicity 40268912/42687703 Mallard duck Acceptable No

--

40696902/42065005 Bobwhite quail Acceptable

850.2300 Avian reproduction

Gamebird and Waterfowl species No data available Yes Adverse effects of possible sublethal exposure at low doses are unknown, and avian reproduction studies are needed to establish a no

observable

- adverse

- effects concentration

. Non

guideline Avian dietary toxicity

– secondary 46656501 Supplemental No

--

Non

guideline Wild mammal acute dietary toxicity

– secondary 46656501 Supplemental No

--

850.3020 Honey bee
acute adult
contact toxicity No data available No These data are not needed at this time for risk assessment of currently registered uses

Bait box use not expected to result in exposure to honey bees Special Study Honey bee adult acute oral toxicity No data available No

850.3030 Honey bee residue on foliage No data available No

Special Study Honey bee adult chronic oral toxicity No data available No

Special Study Honey bee larval chronic oral toxicity No data available No

850.3040 Field testing for pollinators No data available No

### 26 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classification Are data needed for risk assessment ? Jus tification and Assumptions EPA will Make in Absence of Data

850.4100 S eedling E mergence and Seedling Growth No data available No Data not needed as this exposure pathway is not determined to be relevant based on the nature of application of bait placement 850.4150 V egetative V igor No data available No



# 12.0 References

Cox, P. and R.H. Smith. 1992. Rodenticide ecotoxicology: pre

- lethal effects of anticoagulants on rat behavior. Proc. Vertebr. Pest Conf. 15:165

- 170. Pelfrene, A.F. 1991. Synthetic organic rodenticides. Handbook of Pesticide Toxicology, vol. 3: Classes of P esticides, pages 1271

- 1316. Academic Press, Inc. USEPA. 1998a. Guidelines for Ecological Risk Assessment . United States Environmental Protection Agency (USEPA). Risk Assessment Forum. Office of Research and Development. USEPA. 1998b. Reregistration Eligibility Decision (RED): Rodenticide Cluster. EPA738

- R

- 98

- 007. 319 pp. http://www.epa.gov/pesticides/reregistration/status_page_r.htm#rod enticides (accessed 08/25/2015), and see docket EPA

- HQ

- OPP

- 2006

- 0955, available at www.regulations.gov

. USEPA. 2004a. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs

. Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://archive.epa.gov/pesticides/reregistration/web/pdf/ecorisk

- overview.pdf (accessed 10/23/2015). USEPA. 2004b. Potential Risks of Nine Rodenticides to Birds and Nontarget Mammals: A Comparative Approach. Environmental Fate and Effects Division. Office of Pesticide Programs. USEPA. 2008a. OPPTS 835.6100 Terrestrial Field Dissi pation . EPA 712

- C

- 08

- 020. October 2008. Office of Chemical Safety and Pollution Prevention (formerly Office of Prevention, Pesticides, and Toxic Substances). United States Environmental Protection Agency. Available at http://www2.epa.gov/test

- guidelines

- pesticides

- and

- toxic

- substances/series

835

- fate

- transport

- and

- transformation

- test (accessed 10/23 /2015). USEPA . 2008b. Risk Mitigation Decision for Ten Rodenticides (EPA

- HQ

- OPP

- 2006

- 0955

- 0764). Office of Chemical Safety and Pollution Prevention (formerly Office of Prevention, Pesticides, and Toxic Substances). Office of Pesticides Program. Available at www.regulations.gov

. USEPA. 2011. Risks of Difethialone Use to the Federally Threatened Alameda Whipsnake ( Masticophis lateralis euryxanthus ), and the Federally Endangered Salt Marsh Harvest Mouse ( Reithrodontomys raviventris ) and San Joaquin Kit Fox ( Vulpes macrotis mutica ). Pesticide Effects Determination. Environmental Fate and Effects Division. Office of Pesticide Programs. September 30, 2011. Available at

### 27 http://iaspub.epa.gov/apex/pesticides/f?p=CHEMICALSEARCH:7:0::NO:1,3,31,7,12,25: P3_XCHEMICAL_ID:2138 (accessed 10/23 /2015). USEPA. 2015. Estimation Programs Interface SuiteTM for Microsoft ® 

### Windows, v 4.11. Unite d States Environmental Protection Agency, Washington, DC, USA. Available at http://www2.epa.gov/tsca

- screening

- tools/epi

- suitetm

- estimation

- program

- interface (site accessed 10/23 /2015). Saravanan, K. and Kanakasabai, R. (2004). Evaluation of Secondary Poisoning of Difethialone, a New Second

- Generation Anticoagulant Rodenticide to Barn Owl, Tyto alba Hartert Under Captivity. Indian J. Exp. Biol. 42: 1013

- 1016. Ecotox 151510 Vandenbroucke, V., Desmet, N., De Backer, P., and Croubels, S. (2008). Multi

- Residue Analysis of Eight Anticoagulant Rodenticides in Animal Plasma and Liver Using Liquid Chromatography Combined with Heated Electrospray Ionization Tandem Mass Spectrometry. J. Chromatogr. B 869: 101

- 110. ECOTOX 151507 Albert, C. A., Wilson, L. K., Mineau, P., Trudeau, S., and Elliott, J. E. ( Anticoagulant Rodenticides in Three Owl Species From Western Canada, 1988

- 2003. Arch environ contam toxicol. 2010, feb; 58(2):451

- 9. [Archives of environmental contamination and toxicology]: Arch Environ mental Contam ination Toxicol ogy

.

### 28 

# Appendix A. Bibliography of Studies Submitted to EPA

Fate and Chemistry Studies

161

- 1 Hydrolysis

MRID Citation Reference

40268902 Spare, W. (1986) Determination of the Hydrolysis Rate Constants of LM

- 2219: [Final Report]: Lab Project ID: 1403. Unpublished study prepared by Agrisearch Inc. 37 p.



## 161

- 2 Photodegradation

- water

MRID Citation Reference

42785801 Spare, W. (1987) Determination of the Solution Photolysis Rate of LM

- 2219 (Difethialone): Lab Project Number: 1404. Unpublished study prepared by Agrisearch Inc. 53 p.



## 162

- 1 Aerobic soil metabolism

MRID Citation Reference

42785802 Spare, W. (1987) Aerobic Soil Metabolism of LM

- 2219 (Difethialone): Lab Project Number: 1401. Unpublished study prepared by Agrisearch Inc. 72 p.



## 163

- 1 Leach/adsorption/desorption

MRID Citation Reference

42628109 Spare, W. (1992) Adsorption/Desorption of Difethialone: Amended Final Report: Lab Project Number: 1421. Unpublished study prepared by Agrisearch Inc. 98 p.

### 29 

## 128967 Difethialone Ecological Effects Studies

71

- 1 Avian Single Dose Oral Toxicity

MRID Citation Reference

40696901 42065004 Fletcher, D. (1988) 30

- Day Acute Oral Toxicity Study with LM

- 2219 Technical in Bobwhite Quail: Project ID: 87 QD 93. Unpublished study prepared by Bio

Life Associates, Ltd. 39 p.

40268913 42687702 supplement Lorgue, G. (1987) Determination of LD

- 50 of LM

- 2219 Given Orally to the Japanese Quail (Coturnix coturnix): Lab Project ID: 86/3. Unpublished study prepared by Ecotoxicology Lab. 37 p.



## 71

- 2 Avian Dietary Toxicity

MRID Citation Reference

40268912 42687703

- supplement Fletcher, D. (1986) 30

- day Dietary LC50 Study with LM

- 2219 Tech

- nical in Mallard Ducklings: [Final Report]: Lab Project ID: BLAL No. 85 DC 64. Unpublished study prepared by Bio

- Life Associates, Ltd. 111 p.

40268913 Lorgue, G. (1987) Determination of LD

- 50 of LM

- 2219 Given Orally to the Japanese Quail (Coturnix coturnix): Lab Project ID: 86/3. Unpublished study prepared by Ecotoxicology Lab. 37 p.

40696902 42065005 Fletcher, D. (1988) 30

- Day Dietary LC50 Study with LM

- 2219 T echnical in Bobwhite Quail: Project ID: 87 QC 89. Unpublished study prepared by Bio

Life Associates, Ltd. 38 p.

42065005 Fletcher, D. (1988) 30

- Day Dietary LC50 Study with LM

- 2219 Technical in Bobwhite Quail: Lab Project Number: 87

- QC 89. Unpublished stu dy prepared by Bio

- Life Associates, Ltd. 41 p.



## 72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

40268914 Nicholson, R.; Surprenant, D. (1986) Acute Toxicity of LM

- 2219 to Rainbow Trout, Bluegill, and Daphnids: Lab Project IDs: BW

- 86

- 7

- 2081, BW

- 86

- 7

- 2079, BQ

- 86

- 7

- 2080. Unpublished study prepared by Springborn Bionomics, Inc. 59 p.

### 30 

## 72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

40268914 Nicholson, R.; Surprenant, D. (1986) Acute Toxicity of LM

- 2219 to Rainbow Trout, Bluegill, and Daphnids : Lab Project IDs: BW

- 86

- 7

- 2081, BW

- 86

- 7

- 2079, BQ

- 86

- 7

- 2080. Unpublished study prepared by Springborn Bionomics, Inc. 59 p.



## NON Guideline Selections

40268916 Lorgue , G. (1985) Activity and Attractiveness Studies of LM

- 2219 Rodenticide Compound Against Field Rodents: (Translation from Original French Report): Lab Project ID: 22

- 6

- 85. Unpublished study prepared by National Veterinarian School of Lyon. 33 p.

42065009 Belleville, M. (1991) Compared Hepatic Kinetics of Brodifacoum and Difethialone in the Rat After Oral Administration of 0.06 mg/kg Once Weekly for 4 Consecutive Weeks: Lab Project Number: L

- AV/ VN. Unpublished study prepared by Lipha Research Center. 39 p.

42065010 Belleville, M. (1986) Toxi

- Kinetics and Metabolism: Study Performed with the Molecule Marked Carbon 14: Study Performed with the Cold Molecule: Lab Project Number: T

- RAD/LM

- 2219

- 5

- 85

- 3. Unpub

- lished study prepared by Lyonnaise Industrielle Phar maceutique. 133 p.

46656501 Savarie, P. (2005) Secondary Toxicity Hazard Assessment of Difethialone in Black

- Billed Magpies (Pica pica) and European Ferrets (Mustela putoris furo). Project Number: QA/385. Unpublished study prepared by U.S. Dept. of Agricu lture, APHIS, ADC. 194 p.

48396203 Byers, R.; Carbaugh, D. (1991) Rodenticides for the Control of Pine and Meadow Voles in Orchards (Diphacinone, Chlorophacinone, Bromadiolone, Difethialone, Zinc Phosphide, Cholecalciferol, and Oxytetracycline). Journal of Environmental Horticulture 9 (3): 167

- 172.

### 31 

# Appendix B. EPI Suite v.4. 11 Output File for Difethialone

CAS Number: 104653

- 34

- 1 SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

------------------------------ EPI SUMMARY (v4.11)

--------------------------

Physical Property Inputs: Log Kow (octanol

- water):

------ Boiling Point (deg C) :

------ Melting Point (deg C) : 234.50 Vapor Pressure (mm Hg ) : 5.55E

- 007 Water Solubility (mg/L): 0.39 Henry LC (atm

- m3/mole) :

------

KOWWIN Program (v1.68) Results:

===============================

Log Kow(version 1.68 estimate): 9.82

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

------- +

----- +

-------------------------------------------- +

--------- +

--------

TYPE | NUM | LOGKOW FRAGMENT DESCRIPTION | COEFF | VALUE

------- +

----- +

-------------------------------------------- +

--------- +

--------

Frag | 2 |

- CH2

- [aliphatic carbon] | 0.4911 | 0.9822 Frag | 2 |

- CH [aliphatic carbon] | 0.3614 | 0.72 28 Frag | 2 | =CH

- or =C< [olefinc carbon] | 0.3836 | 0.7672 Frag | 24 | Aromatic Carbon | 0.2940 | 7.0560 Frag | 1 |

- Br [bromine, aromatic attach] | 0.8900 | 0.8900 Frag | 1 |

- S

- [aliphatic sulfur,one aromatic attach]| 0.0535 | 0.0535 Frag | 1 |

- OH [alcohol, olefinic attach] |

- 0.8855 |

- 0.8855 Frag | 1 |

- C(=O)

- S [thioester, olefinic attach] |

- 0.7000 |

- 0.7000 Factor| 1 |

- C(=O)

- S

- aromatic correc tion | 0.7000 | 0.7000 Const | | Equation Constant | | 0.2290

------- +

----- +

-------------------------------------------- +

--------- +

-------- Log Ko w = 9.8152

MPBPVP (v1.43) Program Results:

=============================== Experimental Database Structure Match: Name : Difethialone CAS Num : 104653

- 34

- 1 Exp MP (deg C): 234.5 Exp BP (deg C):

--- Exp VP (mm Hg): 5.55E

- 07 (Pa ): 7.40E

- 005 Exp VP (deg C): 25 Exp VP ref : TOMLIN,C (1997)

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

------------------------ SUMMARY MPBVP v1.43

--------------------

### 32 Boiling Point: 687.27 deg C (Adapted Stein and Brown Method)

Melting Point: 349.84 deg C (Adapted Joback Method) Melting Point: 287.64 deg C (Gold and Ogle Method) Mean Melt Pt : 318.74 deg C (Joback; Gold,Ogle M ethods) Selected MP: 300.08 deg C (Weighted Value)

Vapor Pressure Estimations (25 deg C): (Using BP: 687.27 deg C (estimated)) (Using MP: 234.50 deg C (user entered))

VP: 1.27E

- 026 mm Hg (Antoine Method) : 1.69E

- 024 Pa (Antoine Method) VP: 1.34E

- 018 mm Hg (Modified Grain Method) : 1.78E

- 016 Pa (Modified Grain Method) VP: 6.38E

- 015 mm Hg (Mackay Method) : 8.51E

- 013 Pa (Mackay Method) Selected VP: 1.34E

- 018 mm Hg (Modifie d Grain Method) : 1.78E

- 016 Pa (Modified Grain Method) Subcooled liquid VP: 6.55E

- 005 mm Hg (25 deg C, user

- entered VP ) : 0.00873 Pa (25 deg C, user

- entered VP )

------- +

----- +

-------------------- +

---------- +

----- ----

TYPE | NUM | BOIL DESCRIPTION | COEFF | VALUE

------- +

----- +

-------------------- +

---------- +

---------

Group | 2 |

- CH2

- (ring) | 26.44 | 52.88 Group | 2 | >CH

- (ring) | 21.66 | 43.32 Group | 2 | =C< (ring) | 28.19 | 56.38 Group | 1 |

- OH (alcohol) | 106.27 | 106.27 Group | 1 | >C=O (ring) | 94.76 | 94.76 Group | 1 |

- S

- (ring) | 69.00 | 69.00 Group | 16 | CH (aromatic) | 28.53 | 456.48 Group | 6 |

- C (aromatic) | 30.76 | 184.56 Group | 2 | C (3a aromatic) | 45.46 | 90.92 Group | 1 |

- Br (to aromat) | 61.85 | 61.85 * | | Equation Constant | | 198.18

=============+====================+==========+ ========= RESULT

- uncorr| BOILING POINT in deg Kelvin | 1414.60
RESULT

- corr | BOILING POINT in deg Kelvin | 960.43 | BOILING POINT in deg C | 687.27

-------------------------------------------------------

------- +

----- +

-------------------- +

---------- +

---------

TYPE | NUM | MELT DESCRIPTION | COEFF | VALUE

------- +

----- +

-------------------- +

---------- +

---------

Group | 2 |

- CH2

- (ring) | 7.75 | 15.50 Group | 2 | >CH

- (ring) | 19.88 | 39.76 Group | 2 | =C< (ring) | 37.02 | 74.04 Group | 1 |

- OH (alcohol) | 44.45 | 44.45 Group | 1 | >C=O (ring) | 75.97 | 75.97 Group | 1 |

- S

- (ring) | 73.93 | 73.93 Group | 16 | CH (aromatic) | 8.13 | 130.08 Group | 6 |

- C (aromatic) | 37.02 | 222.12 Group | 2 | C (3a aromatic) | 37.02 | 74.04 Group | 1 |

- Br (to aromat) | 43.43 | 43.43 * | | Equation Constant | | 12 2.50

=============+====================+==========+========= RESULT | MELTING POINT in deg Kelvin | 915.82
RESULT

- limit| MELTING POINT in deg Kelvin | 623.00 | MELTING POINT in deg C | 349.84

------------------------------ -------------------------

### 33 Water Sol from Kow (WSKOW v1.42) Results:

========================================

Water Sol: 2.404e

- 007 mg/L

Experimental Water Solubility Database Match: Name : Difethialone CAS Num : 104653

- 34

- 1 Exp WSol : 0.39 mg/L (25 deg C) Exp Ref : TOMLIN,C (1994)

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

---------------------------------- WSKOW v1.42 Results

------------------------ Log Kow (estimated) : 9.82 Log Kow (experimental): not available from database Log Kow used by Water solubility estimates: 9.82

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.693

- 0.96 log Kow

- 0.0092(Tm

- 25)

- 0.00314 MW + Correction

Melting Pt (Tm) = 234.50 deg C (Use Tm = 25 for all liquids)

Correction(s): Value

-------------------- -----

No Applicable Correction Factors

Log Water Solubility (in moles/L) :

- 12.351 Water Solubility at 25 deg C (mg/L): 2.404e

- 007

WATERNT Program (v1.01) Results:

===============================

Water Sol (v1.01 est): 5.3949e

- 007 mg/L

Experimental Water Solubility Database Match: Name : Difethialone CAS Num : 104653

- 34

- 1 Exp WSol : 0.39 mg/L (25 deg C) Exp Ref : TOMLIN,C (1994)

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

- ------ +

----- +

-------------------------------------------- +

---------- +

---------

TYPE | NUM | WATER SOLUBILITY FRAGMENT DESCRIPTION | COEFF | VALUE

------- +

----- +

-------------------------------------------- +

---------- +

---------

Frag | 2 |

- CH [aliphatic carbon] |

- 0.5285 |

- 1.0570 Frag | 2 | =CH

- or =C< [olefinc carbon] |

- 0.3646 |

- 0.7292 Frag | 16 | Aromatic Carbon (C

- H type) |

- 0.3359 |

- 5.3738 Frag | 1 |

- Br [bromine, ar omatic attach] |

- 0.5661 |

- 0.5661 Frag | 1 |

- S

- [aliphatic sulfur,one aromatic attach]|

- 0.4239 |

- 0.4239 Frag | 8 | Aromatic Carbon (C

- substituent type) |

- 0.5400 |

- 4.3196 Frag | 2 |

- CH2

- [aliphatic carbon, cyclic] |

- 0.3308 |

- 0.6617 Frag | 1 |

- OH [alcohol, olefinic attach] | 0.0000 | 0.0000 Frag | 1 |

- C(=O)

- S [thioester, aliphatic attach] | 0.5890 | 0.5890 Const | | Equation Constant | | 0. 2492

------- +

----- +

-------------------------------------------- +

---------- +

---------

### 34 NOTE | | Minimum Solubility (log S =

- 12.00) Applied! |

------- +

----- +

-------------------------------------------- +

---------- +

--------- Log Water Sol (moles/L) at 25 dec C =

- 12.0000 Water Solubility (mg/L) at 25 dec C =5.3949e

- 007

ECOSAR Program (v1.11) Results:

=============================== ECOSAR Version 1.11 Results Page

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone
CAS Num: ChemID1: MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49 Log Kow: 9.815 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Ko w: (PhysProp DB exp value

- for comparison only) Melt Pt: 234.50 (deg C, User Entered for Wat Sol estimate) Melt Pt: 234.50 (deg C, PhysProp DB exp value for Wat Sol est) Wat Sol: 2.404E

- 007 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat S ol: 0.39 (mg/L, User Entered) Wat Sol: 0.39 (mg/L, PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 9.815 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 0.39 (mg/L, User Entered)

-------------------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Esters Vinyl/Allyl Alcohols Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Esters : Fish 96

- hr LC50 0.00197 Esters : Daphnid 48

- hr LC50 0.00177 Esters : Green Algae 96

- hr EC50 0.000219 Esters : Fish ChV 2.87e

- 005
Esters : Daphnid ChV 0.000128 Esters : Green Algae ChV 0.000709 Esters : Fish (SW) 96

- hr LC50 0.00185 Esters : Mysid 96

- hr LC50 3.88e

- 005 Esters : Fish (SW) ChV 0.00109 Esters : Mysid (SW) ChV 3.45e

- 010 Esters : Earthworm 14

- day LC50 21.260 *

Vinyl/Allyl Alcohols : Fish 96

- hr LC50 0.708 * Vinyl/Allyl Alcohols : Daphnid 48

- hr LC50 0.188 Vinyl/Allyl Alcohols : Green Algae 96

- hr EC50 0.002 Vinyl/ Allyl Alcohols : Fish ChV 4.71e

- 005 ! Vinyl/Allyl Alcohols : Daphnid ChV 0.000219 ! Vinyl/Allyl Alcohols : Green Algae ChV 0.004

=========================== ================== ======== ====== ==========

### 35 Neutral Organic SAR : Fish 96

- hr LC50 4.24e

- 005 (Baseline Toxicity) : Daphnid 48

- hr LC50 4.96e

- 005 : Green Algae 96

- hr EC50 0.00073 : Fish ChV 9.72e

- 006 : Daphnid ChV 3.6e

- 005 : Green Algae ChV 0.000953

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES)

a re reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- chronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------- ----------------------- Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effects at saturation are expected for those endpoints.

Esters:

- ----- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50, Mysid LC50) Maximum LogKow: 6.0 (Earthworm LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

Vinyl/Allyl Alcohols:

-------------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

HENRYWIN (v3. 20) Program Results:

=============================

Bond Est : 1.04E

- 013 atm

- m3/mole (1.05E

- 008 Pa

- m3/mole) Group Est: Incomplete

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------- HENRYWIN v3.20 Results

--------------------------

Experimental Database Structure Match: Name : Difethialone CAS Num : 104653

- 34

- 1 Exp HLC : 1.00E

- 06 atm

- m3/mole (0.1 01 Pa

- m3/mole)

### 36 Temper : 25 deg C Exp Ref : VP/WSOL

---------- +

--------------------------------------------- +

--------- +

---------- CLASS | BOND CONTRIBUTION DESCRIPTION | COMMENT | VALUE

---------- +

---------------------------- ----------------- +

--------- +

----------

HYDROGEN | 6 Hydrogen to Carbon (aliphatic) Bonds | |

- 0.7181 HYDROGEN | 16 Hydrogen to Carbon (aromatic) Bonds | |

- 2.4687 HYDROGEN | 1 Hydrogen to Oxygen Bonds | | 3.2318 FRAGMENT | 3 C

- C | | 0.3489 FRAGMENT | 3 C

- Car | | 0.4858 FRAGMENT | 1 C

- Cd | | 0.0635 FRAGMENT | 24 Car

- Car | | 6.3314 FRAGMENT | 1 Car

- Br | | 0.2454 FRAGMENT | 1 Car

- S | | 0.6345 FRAGMENT | 1 Cd

- CO | | 1.9260 FRAGMENT | 1 Car

- Car Ring

- to

- Ring (biphenyl

- type) | | 0.1490 FRAGMENT | 1 CO

- S | ESTIMATE| 0.5000 FRAGMENT | 1 Cd

- O | | 0.2 051 FRAGMENT | 1 Car

- Cd | | 0.4371 FRAGMENT | 1 Cd=Cd | | 0.0000

---------- +

--------------------------------------------- +

--------- +

----------

RESULT | BOND ESTIMATION METHOD for LWAPC VALUE | TOTAL | 11.372

---------- +

--------------------------------------------- +

--------- +

---------- HENRYs LAW CONSTANT at 25 deg C = 1.04E

- 013 atm

- m3/mole = 4.25E

- 012 un itless = 1.05E

- 008 Pa

- m3/mole

-------- +

----------------------------------------------- +

------------ +

-------- | GROUP CONTRIBUTION DESCRIPTION | COMMENT | VALUE

-------- +

------------------------- ---------------------- +

------------ +

-------- | 1 Cd (C)(CO) | ESTIMATE | 0.10 | 1 CH2 (C)(C) | |

- 0.15 | 1 CH2 (C)(Car) | |

- 0.19 | 1 CH (C)(C)(Car) | | 0.29 | 16 Car

- H (Car)(Car) | | 1.76 | 3 Car (C)(Car)(Car) | | 2.10 | 2 Car (Car)(Car)(Car) external | ESTIMATE | 0.66 | 1 Car (Car)(Car)(Br) | | 0.49 | 1 Car (Car)(Car)(S) | |

- 0.25 | 1 Car (Ca r)(Car)(Cd) | ESTIMATE | 0.75 | MISSING Value for: CO (Cd)(S) | MISSING Value for: S (Car)(CO) | MISSING Value for: Cd (O)(Car) | MISSING Value for: O

- H (Cd) | MISSING Value for: CH (C)(Car)(Cd)

-------- +

----------------------------------------------- +

------------ +

--------

RESULT | GROUP ESTIMATION METHOD for LOG GAMMA VALUE | INCOMPLETE | 5.56

-------- +

------------------------- ---------------------- +

------------ +

--------

For Henry LC Comparison Purposes: Exper Database: 1.00E

- 06 atm

- m3/mole (1.01E

- 001 Pa

- m3/mole)
User

- Entered Henry LC: not entered Henrys LC [via VP/WSol estimate using User

- Entered or Estimated values]: HLC: 1.010E

- 006 atm

- m3/mole (1.024E

- 001 Pa

- m3/mole) VP: 5.55E

- 007 mm Hg (source: User

- Entered) WS: 0.39 mg/L (source: User

- Entered)

Log Octanol

- Air (KOAWIN v1.10) Results:

====== ================================

### 37 Log Koa: 14.208

SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------- KOAWIN v1.10 Results

---------- ----------------

Log Koa (octanol/air) estimate: 14.208 Koa (octanol/air) estimate: 1.616e+014 Using: Log Kow: 9.82 (KowWin est) HenryLC: 1e

- 006 atm

- m3/mole (exp database) Log Kaw:

- 4.388 (air/water part.coef.)

LogKow :

---- (exp database) LogKow : 9.82 (KowWin estimate) Henry LC: 1e

- 006 atm

- m3/mole (exp database) Henry LC: 1.04e

- 013 atm

- m3/mole (HenryWin bond estimate)

Log Koa (octanol/air) estimate: 21.191 (from KowWin/HenryWin)

BIOWIN (v4.10) Program Results:

============================== SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------- BIOWIN v4.10 Results

----------------------------

Biowin1 (Linear Model Prediction) : Biodegrades Fast Biowin2 (Non

- Linear Model Prediction): Does Not Biodegrade Fast Biowin3 (Ultimate Biodegradation Timeframe): Months Biowin4 (Primary Biodegradation Timeframe): Weeks Biowin5 (MITI L inear Model Prediction) : Does Not Biodegrade Fast Biowin6 (MITI Non

- Linear Model Prediction): Does Not Biodegrade Fast Biowin7 (Anaerobic Model Prediction): Does Not Biodegrade Fast Ready Biodegradability Prediction: NO

------ +

----- +

---- ---------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin1 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphatic alcohol [

- OH] | 0.1587 | 0.1587 Frag | 1 | Aromatic bromide [

- Br] |

- 0.1103 |

- 0.1103 Frag | 3 | Alkyl substituent on aromatic ring | 0.0547 | 0.1640 MolWt| * | Molecular Weight Parameter | |

- 0.2568 Const| * | Equation Constant | | 0.7475

============+============================================+=========+========= RESULT | Biowin1 (Linear Biodeg Probabili ty) | | 0.7031

============+============================================+=========+=========

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin2 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphatic alcohol [

- OH] | 1.1178 | 1.1178 Frag | 1 | Aromatic bromide [

- Br] |

- 1.6779 |

- 1.6779 Frag | 3 | A lkyl substituent on aromatic ring | 0.5771 | 1.7313 MolWt| * | Molecular Weight Parameter | |

- 7.6608

============+============================================+=========+========= RESULT | Biowin2 (Non

- Linear Biode g Probability) | | 0.0299

### 38 ============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates

-- > Biodegrades Fast A Probability Less Than 0.5 indicates

-- > Does NOT Biodegrade F ast

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin3 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | A liphatic alcohol [

- OH] | 0.1600 | 0.1600 Frag | 1 | Aromatic bromide [

- Br] |

- 0.1360 |

- 0.1360 Frag | 3 | Alkyl substituent on aromatic ring |

- 0.0749 |

- 0.2246 MolWt| * | Molecular Weight Parameter | |

- 1.1922 Const| * | Equation Constant | | 3.1992

============+============================================+=========+========= RESULT | Biowin3 (Survey Model

- Ultimate Biodeg) | | 1.8064

============+============================================+=========+=========

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin4 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

- ---- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphatic alcohol [

- OH] | 0.1294 | 0.1294 Frag | 1 | Aromatic bromide [

- Br] |

- 0.1535 |

- 0.1535 Frag | 3 | Alkyl substituent on aromatic ring |

- 0.0685 |

- 0.2056 MolWt| * | Molecular Weight Parameter | |

- 0.7784 Const| * | Equation Constant | | 3.8477

============+============================================ +=========+========= RESULT | Biowin4 (Survey Model

- Primary Biodeg) | | 2.8397

============+============================================+=========+=========

Result Classification: 5.00

- > hours 4.00

- > days 3.00

- > weeks

(P rimary & Ultimate) 2.00

- > months 1.00

- > longer

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin5 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

------------------------------ -------------- +

--------- +

---------

Frag | 1 | Aliphatic alcohol [

- OH] | 0.1611 | 0.1611 Frag | 1 | Aromatic bromide [

- Br] | 0.1668 | 0.1668 Frag | 1 | Aromatic

- CH2 |

- 0.0557 |

- 0.0557 Frag | 2 | Aromatic

- CH |

- 0.0098 |

- 0.0195 Frag | 16 | Aromatic

- H | 0.0082 | 0.1315 Frag | 1 |

- CH2

- [cyclic] | 0.0197 | 0.0197 MolWt| * | Molecular Weight Parameter | |

- 1.6050 Const| * | Equation Constant | | 0.7121

============+============================================+=========+========= RESULT | Biowin5 (MITI Linear Bio deg Probability) | |

- 0.4889

============+============================================+=========+=========

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin6 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphatic alcohol [

- OH] | 1.0041 | 1.0041 Frag | 1 | Aromatic bromide [

- Br] | 1.5021 | 1.5021 Frag | 1 | Aromatic

- CH2 |

- 0.1246 |

- 0.1246 Frag | 2 | Aromatic

- CH | 0.2624 | 0.5248 Frag | 16 | Aromatic

- H | 0.1201 | 1.9223 Frag | 1 |

- CH2

- [cyclic] | 0.2365 | 0.2365 MolWt| * | Molecular Weight Parameter | |

- 15.5744

============+============================================+=========+========= RESULT |Biowin6 (MITI Non

- Linear Biodeg Probabilit y)| | 0.0003

============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates

-- > Readily Degradable A Probability Less Than 0.5 indicates

-- > NOT Readily Degradable

### 39 ------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | Biowin7 FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphatic alco hol [

- OH] | 0.1328 | 0.1328 Frag | 1 | Aromatic bromide [

- Br] | 0.0000 | 0.0000 Frag | 3 | Alkyl substituent on aromatic ring |

- 0.1145 |

- 0.3434 Frag | 1 | Aromatic

- CH2 |

- 0.0073 |

- 0.0073 Frag | 2 | Aromatic

- CH | 0.0331 | 0.0662 Frag | 16 | Aromatic

- H |

- 0.0954 |

- 1.5269 Frag | 1 |

- CH2

- [cy clic] |

- 0.1200 |

- 0.1200 Const| * | Equation Constant | | 0.8361

============+============================================+=========+========= RESULT | Biowin7 (Anaerobic Linear Biodeg Prob) | |

- 0.9626

============+============================================+=========+=========

A Probability Greater Than or Equal to 0.5 indicates

-- > Biodegrades Fast A Probability Less Than 0.5 indicates

-- > Does NOT Biodegrade Fast

Rea dy Biodegradability Prediction: (YES or NO)

----------------------------------------------

Criteria for the YES or NO prediction: If the Biowin3 (ultimate survey model) result is "weeks" or faster (i.e. "days", "days to weeks", or "weeks" AND the Biowi n5 (MITI linear model) probability is >= 0.5, then the prediction is YES (readily biodegradable). If this condition is not satisfied, the prediction is NO (not readily biodegradable). This method is based on application of Bayesian analysis to ready b iodegradation data (see Help). Biowin5 and 6 also predict ready biodegradability, but for degradation in the OECD301C test only; using data from the Chemicals Evaluation and Research Institute Japan (CERIJ) database.

BioHCwin (v1.01) Program Results:

============================== SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

-------------------------- BioHCwin v1.01 Results

--------------- ------------

NO Estimate Possible ... Structure NOT a Hydrocarbon (Contains atoms other than C, H or S (

- S

- ))

AEROWIN Program (v1.00) Results:

===============================

Sorption to aerosols (25 Dec C)[AEROWIN v1.00]:

Vapor pressure ( liquid/subcooled): 0.00873 Pa (6.55E

- 005 mm Hg) Log Koa (Koawin est ): 14.208

Kp (particle/gas partition coef. (m3/ug)): Mackay model : 0.000344 Octanol/air (Koa) model: 39.6 Fraction sorbed to airborne particulates (p hi): Junge

- Pankow model : 0.0123 Mackay model : 0.0267 Octanol/air (Koa) model: 1

AOP Program (v1.92) Results:

### 40 =========================== SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

------------------- SUMMARY (AOP v1.92): HYDROXYL RADICALS (25 deg C)

-------- Hydrogen Abstraction = 7.8831 E

- 12 cm3/molecule

- sec **Reaction with N, S and

- OH = 1.1400 E

- 12 cm3/molecu le

- sec Addition to Triple Bonds = 0.0000 E

- 12 cm3/molecule

- sec **Addition to Olefinic Bonds = 38.5000 E

- 12 cm3/molecule

- sec **Addition to Aromatic Rings = 10.9586 E

- 12 cm3/molecule

- sec Addition to Fused Rings = 0.0000 E

- 12 cm3/molecule

- sec

OVERALL OH Rate Constant = 58.4817 E

- 12 cm3/molecule

- sec HALF

- LIFE = 0.183 Days (12

- hr day; 1.5E6 OH/cm3)
HALF

- LIFE = 2.195 Hrs ........................ ** Designates Estimation(s) Using ASSUMED Value(s)

------------------- SUMMARY (AOP v1. 91): OZONE REACTION (25 deg C)

----------- OVERALL OZONE Rate Constant = 13.650000 E

- 17 cm3/molecule

- sec HALF

- LIFE = 0.084 Days (at 7E11 mol/cm3)
HALF

- LIFE = 2.015 Hrs

Experimental Database: NO Structure Matches Fraction sorbed to airborne particulates (phi): 0.0195 (Junge

- Pankow, Mackay avg) 1 (Koa method) Note: the sorbed fraction may be resistant to atmospheric oxidation

KOCWIN Program (v2.00) Results:

============================== SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------- KOCWIN v2.00 Results

---------------------------

Koc Estimate from MCI:

--------------------- First Order Molecular Connectivity Index ........... : 17.081
Non

- Corrected Log Koc (0.5213 MCI + 0.60) .......... : 9.5039 Fragment Correction(s): 1 Aliphatic Alcohol (

- C

- OH) ........... :

- 1.3179 1 Misc (C=O) Group (aliphatic attach).... :

- 1.6047 Corrected Log Koc .................................. : 6.5813

Estimated Koc: 3.813e+006 L/kg <===========

Koc Estimate from Log Kow:

------- ------------------ Log Kow (Kowwin estimate) ......................... : 9.82
Non

- Corrected Log Koc (0.55313 logKow + 0.9251) .... : 6.3568 Fragment Correction(s): 1 Aliphatic Alcohol (

- C

- OH) .......... . :

- 0.4114 1 Misc (C=O) Group (aliphatic attach).... :

- 0.2293 Corrected Log Koc .................................. : 5.7161

Estimated Koc: 5.201e+005 L/kg <===========

### 41 HYDROWIN Program (v2.00) Results:

================================ SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------- HYDROWIN v2.00 Results

------------- --------------

Hydrolyzable Function detected: Thioester

- C

- C(=O)

- S

- C

-

Very limited experimental data suggest the hydrolysis rates of these thioesters MAY be similar to the rates of plain esters (

- C

- C(=O)

- O

- C

- ); hydrolysis is b ase

- catalyzed and increases with increasing pH, especially at pH8 and above. Replacing the sulfur atom with an oxygen atom in the SMILES will estimate the hydrolysis rate for the plain
ester.

Experimental Half

- Lives at 20

- 25 deg C (Pest icide Manual): Acibenzolar

- S

- methyl (CAS 135158

- 54

- 2): pH5 (3.8 yr), pH7 (23 weeks), pH9 (19.4 hr) MCPA

- thioethyl (CAS 25319

- 90

- 8): acidic media (stable), pH7 (22 days), pH9 (2 days)

BCFBAF Program (v3.01) Results:

============================== SMILES : O=C1Sc2ccccc2C(O)=C1C3CC(c5ccc(c6ccc(Br)cc6)cc5)Cc4ccccc34 CHEM : Difethialone MOL FOR: C31 H23 Br1 O2 S1 MOL WT : 539.49

--------------------------------- BCFBAF v3.01

--------------------------- ----- Summary Results: Log BCF (regression

- based estimate): 2.74 (BCF = 555 L/kg wet

- wt) Biotransformation Half

- Life (days) : 4.66e+003 (normalized to 10 g fish) Log BAF (Arnot

- Gobas upper trophic): 5.76 (BAF = 5.75e+005 L/kg wet

- wt)

Log Kow (experimental): not available from database Log Kow used by BCF estimates: 9.82

Equation Used to Make BCF estimate: Log BCF =

- 0.49 log Kow + 7.554 + Correction

Correction(s): Value

No Applicable Correction Factors

Estimated Log BCF = 2.745 (BCF = 555.3 L/kg wet

- wt)

=========================================================== Whole Body Primary Biotransformation Rate Estimate for Fish:

===========================================================

------ +

----- +

-------------------------------------------- +

--------- +

---------

TYPE | NUM | LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION | COEFF | VALUE

------ +

----- +

-------------------------------------------- +

--------- +

---------

Frag | 1 | Aliphat ic alcohol [

- OH] |

- 0.0616 |

- 0.0616 Frag | 1 | Aromatic bromide [

- Br] | 0.3964 | 0.3964 Frag | 3 | Alkyl substituent on aromatic ring | 0.1781 | 0.5342 Frag | 1 | Aromatic

- CH2 |

- 0.3365 |

- 0.3365 Frag | 2 | Aromatic

- CH |

- 0.4629 |

- 0.9259

### 42 Frag | 16 | Aromatic

- H | 0.2664 | 4.2620 Frag | 1 |

- CH2

- [cyclic] | 0.0963 | 0. 0963 Frag | 2 | Number of fused acyclic rings | 0.6477 | 1.2953 Frag | 2 | Number of fused 6

- carbon aromatic rings |

- 0.5779 |

- 1.1557 Frag | 1 | Biphenyl |

- 0.5319 |

- 0.5319 Frag | 1 | Tetra lin | 0.0000 | 0.0000 L Kow| * | Log Kow = 9.82 (KowWin estimate) | 0.3073 | 3.0166 MolWt| * | Molecular Weight Parameter | |

- 1.3834 Const| * | Equation Constant | |

- 1.5371

============+============================================+=========+========= RESULT | LOG Bio Half

- Life (days) | | 3.6687 RESULT | Bio Half

- Life (days) | | 4663 NOTE | Bio Half

- Life Normalized to 10 g fish at 15 deg C |

============+============================================+=========+=========

Biotransformation Rate Constant:

kM (Rate Constant): 0.0001486 /day (10 gram fish) kM (Rate Con stant): 8.358e

- 005 /day (100 gram fish) kM (Rate Constant): 4.7e

- 005 /day (1 kg fish) kM (Rate Constant): 2.643e

- 005 /day (10 kg fish)

Arnot

- Gobas BCF & BAF Methods (including biotransformation rate estimates): Estimated Log BCF (upper trophic) = 2.068 (BCF = 117.1 L/kg wet

- wt) Estimated Log BAF (upper trophic) = 5.760 (BAF = 5.752e+005 L/kg wet

- wt) Estimated Log BCF (mid trophic) = 2.248 (BCF = 177.2 L/kg wet

- wt) Estimated Log BAF (mid trophi c) = 5.396 (BAF = 2.491e+005 L/kg wet

- wt) Estimated Log BCF (lower trophic) = 2.304 (BCF = 201.2 L/kg wet

- wt) Estimated Log BAF (lower trophic) = 5.113 (BAF = 1.298e+005 L/kg wet

- wt)

Arnot

- Gobas BCF & BAF Methods (assuming a biotransformati on rate of zero): Estimated Log BCF (upper trophic) = 2.105 (BCF = 127.4 L/kg wet

- wt) Estimated Log BAF (upper trophic) = 5.806 (BAF = 6.393e+005 L/kg wet

- wt)

Volatilization From Water

=========================

Chemical Name: Difethialone

Molecular Weight : 539.49 g/mole Water Solubility : 0.39 ppm Vapor Pressure : 5.55E

- 007 mm Hg Henry's Law Constant: 1E

- 006 atm

- m3/mole (Henry experimental database)

RIVER LAKE

--------- --------- Water Depth (meters): 1 1 Wind Velocity (m/sec): 5 0.5 Current Velocity (m/sec): 1 0.05

HALF

- LIFE (hours) : 1362 1.506E+004
HALF

- LIFE (days ) : 56.76 627.3
HALF

- LIFE (years) : 0.1554 1.718

STP Fugacity Model : Predicted Fate in a Wastewater Treatment Facility

====================================================================== (using 10000 hr Bio P,A,S) PROPERTIES OF: Difethialone

-------------

### 43 Molecular weight (g/mol) 539.4 9 Aqueous solubility (mg/l) 0.39 Vapour pressure (Pa) 7.39939E

- 005 (atm) 7.30263E

- 010 (mm Hg) 5.55E

- 007 Henry 's law constant (Atm

- m3/mol) 1E

- 006 Air

- water partition coefficient 4.0897E

- 005 Octanol

- water partition coefficient (Kow) 6.60693E+009 Log Kow 9.82 Biomass to water partition coefficient 1.32139E+009 Temperature [deg C] 25 Biodeg rate constants (h^

- 1),half life in biomass (h) and in 2000 mg/L MLSS (h):

- Primary tank 0.00 10000.00 10000.00

- Aeration tank 0.00 10000.00 10000.00

- Settling tank 0.00 10000.00 10000.00

STP Overall Chemical Mass Balance:

--------------------------------- g/h mol/h percent

Influent 1.00E+001 1.9E

- 002 100.00

Primary sludge 5.99E+000 1.1E

- 002 59.89 Waste sludge 3.34E+000 6.2E

- 003 33.36 Primary volatilization 2.05E

- 009 3.8E

- 012 0.00 Settling volatilization 4.54E

- 009 8.4E

- 012 0.00 Aeration off gas 1.12E

- 008 2.1E

- 011 0.00

Primary biodegradation 1.75E

- 002 3.2E

- 005 0.18 Settling biodegradation 4.26E

- 003 7.9E

- 006 0.04 Aeration biodegradation 5.61E

- 002 1.0E

- 004 0.56

Final water effluent 5.96E

- 001 1.1E

- 003 5.96

Total r emoval 9.40E+000 1.7E

- 002 94.04 Total biodegradation 7.79E

- 002 1.4E

- 004 0.78

Level III Fugacity Model (Full

- Output):

======================================= Chem Name : Difethialone Molecular Wt : 539.49 Henry's LC : 1e

- 006 atm

- m3/mole (Henry database) Vapor Press : 5.55e

- 007 mm Hg (user

- entered) Liquid VP : 6.55e

- 005 mm Hg (super

- cooled) Melting Pt : 235 deg C (user

- entered) Log Kow : 9.82 (Kowwin program) Soil Koc : 3.81e+006 (KOCWIN MCI method)

Mass Amount Half

- Life Emissions

(percent) (hr) (kg/hr) Air 0.0359 1.38 1000 Water 12 1.44e+003 1000 Soil 77.2 2.88e+003 1000 Sediment 10.9 1.3e+004 0

Fugacity Reaction Advection Reaction Advection

(atm) (kg/hr) (kg/hr) (percent) (percent) Air 8.67e

- 013 974 19.4 32.5 0.647 Water 1.78e

- 014 311 647 10.4 21.6 Soil 4.7e

- 015 1e+003 0 33.5 0 Sediment 2.97e

- 014 31.4 11.7 1.05 0.392

### 44 Persistence Time: 1.8e+003 hr Reaction Time: 2.33e+003 hr Advection Time: 7.98e+003 hr Percent Reacted: 77.4 Percent Advected: 22.6

Half

- Lives (hr), (based upon Biowin (Ultimate) and Aopwin): Air: 1.381 Water: 1440 Soil: 2880 Sediment: 1.296e+004 Biowin estimate: 1.806 (months )

Advection Times (hr): Air: 100 Water: 1000 Sediment: 5e+004

### 45 

# Appendix C

. SIPS Model I nput/Output Summary

Table 1. Inputs Parameter Value Chemical name Difethialone Solubility (in water at 25 o C; mg/L) 0.39

Mammalian LD 50 (mg/kg

- bw) 0.55 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 0 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 0.26 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor

Mallard NOAEC (mg/kg

- diet) 0.5 Bobwhite quail NOAEC (mg/kg

- diet) 0.25 NOAEC (mg/kg

- diet) for other bird species 0.95 Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.0671 0.0671 Adjusted toxicity value (mg/kg

- bw) 0.4230 0.0000 Ratio of exposure to toxicity 0.1586 0.0000

Conclusion* Exposure through drinking water alone is a

potential concern for mammals Due to insufficient data, risk cannot be precluded

Table 3. Avian Results Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.3159 0.3159 Adjusted toxicity value (mg/kg

- bw) 2.3140 #DIV/0! Ratio of exposure to acute toxicity 0.1365 #DIV/0!

### 46 Conclusion* Exposure through drinking water alone is a

potential concern for birds #DIV/0!

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.

### 47 

## APPENDIX D

. 

# Active Registrations For 128967 / 104653

- 34

- 1 / Difethialone

Registration # Registration Name Company Name Current Status % of Active Ingredient

3282

- 110 DIFETHIALONE MINI BLOCKS RECKITT BENCKISER LLC Active

- Conditionally Registered (01

- Apr

2003) .0025

7173

- 204 DIFETHIALONE TECHNICAL LIPHATECH, INC. Active

- Registered (03

- May

- 1995) 98.6

7173

- 205 GENERATION PELLETS LIPHATECH, INC. Active

- Registered (03

- May

- 1995) .0025

7173

- 211 GENERATION RODENTICIDE BAIT PACKS (PELLETS) LIPHATECH, INC. Active

- Registered (03

- May

- 1995) .0025

7173

- 218 GENERATION MINI BLOCKS LIPHATECH, INC. Active

- Conditionally Registered (24

- Oct

1995) .0025

7173

- 223 DIFETHIALONE 0.125% LIQUID CONCENTRATE LIPHATECH, INC. Active

- Conditionally Registered (13

- Mar

1998) .125

7173

- 224 DIFETHIALONE 0.5% DRY CONCENTRATE LIPHATECH, INC. Active

- Conditionally Registered (07

- Jun

1999) .5

7173

- 226 GENERATION BLOCK LIPHATECH, INC. Active

- Conditionally Registered (08

- May

2003) .0025

7173

- 229 GENERATION BLUE PELLETS LIPHATECH, INC. Active

- Conditionally Registered (31

- Oct

2003) .0025

7173

- 231 DIFETHIALONE 0.125% LIQUID CONCENTRATE WITH DENATONIUM BENZOATE LIPHATECH, INC. Active

- Conditionally Registered (20

- Feb

2004) .125

7173

- 238 GENERATION MEAL LIPHATECH, INC. Active

- Reg istered (09

- Feb

- 2005) .0025

7173

- 258 DIFETHIALONE PASTE PLACE PACKS LIPHATECH, INC. Active

- Conditionally .0025

### 48 7173

- 258 DIFETHIALONE PASTE PLACE PACKS LIPHATECH, INC. Active

- Conditionally Registered (27

- Aug

2007) .0025

7173

- 288 DIFETHIALONE BLOCK 0707 LIPHATECH, INC. Active

- Conditionally Registered (22

- Oct

2009) .0025

7173

- 300 DIFETHIALONE MINI BLOCK 0111 LIPHATECH, INC. Active

- Registered (24

- Aug

- 2011) .0025

7173

- 302 DIFETHIALONE BLOCK 1102 LIPHATECH, INC. Active

- Registered (11

- Jul

- 2012) .0025

AZ110002 DIFETHIALONE PASTE PLACE PACKS LIPHATECH, INC. Active

- Registered (26

- Oct

- 2011) .0025

7173

- EUP

- 9 LIPHATECH, INC. Active

- Issued (30

- May

- 1990) .005