UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. D.C. 20460 

March 9, 2016 

MEMORANDUM 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

PC Code 128967 

DP Barcode 429400 

SUBJECT: Problem Formulation for Registration Review of Difethialone 

FROM: 

REVIEWED 

BY: Justin Housenger, Biologist 

Gabriel Rothman, Environmental Scientist 

Environmental Risk Branch V 

Environmental Fate and Effects Division (7507P) .3// 0 / / 0 

THROUGH: Mah T. Shamim, Ph.D .. Branch Chief ;/~-"v - Environmental Risk Branch V 

Environmental Fate and Effects Division (7507P) 

TO: Ricardo Jones, Chemical Review Manager 

Melissa Grable, Team Leader 

Neil Anderson, Branch Chief 

Risk Management and Implementation Branch I 

Pesticide Re-Evaluation Division (7508P) 

Please. find attached the Preliminary Problem Formulation for the Ecological Risk 

Assessment and Drinking Water Exposure Assessment for Registration Review to be conducted 

for Difethialone. 
2

Problem Formulation for the Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support 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 Characterization............................................................................................................ 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 Summary.......................................................................................................... 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 difethialone, 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 consumption of bait product and movement of the ingested

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 will 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 provides 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 been 

submitted to fulfill some conventional environmental fate studies; however, these data are not 

necessary for 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 stations, if exposed to normal rainwater or runoff, and to reach surface water. There is one 

possible exception: the use of the chemical in sewers systems. The concerns for sewer use are that

non-target organisms may visit sewers and/or chunks of bait blocks could be knocked or broken 

off as bait is eaten, discharged with stormwater or sewage overflow, and then consumed by nontarget organisms. For the uses on sewer systems, 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. 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 Requirements

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 uses.

850.2100 Acute Oral Toxicity – Passerine Species

Smaller passerine 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 sublethal 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 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 one 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).

 Second-generation anticoagulants tend to be more acutely toxic than are the firstgeneration 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-epoxide 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 general, 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 rodenticide 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 scavenger, 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 assessments 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 2011 endangered species assessment 

for the Alameda whipsnake, salt marsh harvest mouse, and San Joaquin kit fox (USEPA 2011b). 

In 2011 there was a Scientific Advisory Panel (SAP) and Notice of Intent to Cancel (NOIC) NonCompliant Rodenticides. In June of 2013 the California Department of Pesticide 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 difethialone, 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 anticoagulants (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 grocery 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 enduse 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 premises), commercial transport facilities and 

vehicles, refuse solid waste containers (garbage cans), ships and boats, and in sewers. For outdoor 

applications, rodent control bait containing difethialone must be placed within 100 feet of

structures. Product labels 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 

minimum interval between applications. Instead, labels 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 active ingredient per placement, or the amount of active ingredient per linear 

feet, 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 conservative 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 basis for this scoping document. An 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 2011 an endangered species 

assessment was conducted 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 2011b) 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) To 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 intended 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 

difethialone). 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, two 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-OPP2011-0718.

The primary risk issues have been identified for certain 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 

potential 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 animals poisoned with 

bait.”

In the most recent, comprehensive assessment conducted for difethialone, the endangered 

species assessment (ESA, USEPA 2011b), the major ecological conclusions for risk were as 

follows:

Table 1. Summary of Risk Concerns Identified 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 No1 NA NA Yes2 NA No1 No Yes2 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

Effects on terrestrial and aquatic plant communities were judged to be discountable. 2

Although 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 on difethialone. The 

exclusive use of difethialone bait outdoors in bait stations, the extremely low concentrations in 

bait, and the hydrophobicity of the compound, reduces potential for extraction (leaching) of 

difethialone residues from 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. Aquatic benchmarks have been established for 

difethialone (available at http://www.epa.gov/pesticide-science-and-assessing-pesticiderisks/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 physicochemical 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 Difethialone2

 2 The structure was obtained from the difethialone data sheet available at 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 C31H23BrO2S N/A

CAS Name

3-[3-(4′-bromo[1,1′-biphenyl]-4-yl)-1,2,3,4-

tetrahydro-1-naphthalenyl]-4-hydroxy-2H-1-

benzothiopyran-2-one

Difethialone data sheet

IUPAC Name

3-[(1RS,3RS;1RS,3SR)-3-(4′-bromobiphenyl-4-yl)-

1,2,3,4-tetrahydro-1-naphthyl]-4-hydroxy-1-

benzothiin-2-one where the ratios of the racemates 

(1RS,3RS) to (1RS,3SR) lie within the ranges 0–15 to 

85–100 respectively

Difethialone data sheet

Bulk Density 1.3614 g/cm3 at 250C MRID 42065002

Vapor Pressure 0.074 mPa = 5.55x10-7 mm Hg @ 25o

C

‘Non-volatile from a field condition’

EPI Suite v.4.11

USEPA, 2008a

Henry’s Law Constant 1.00 x 10-6 atm-m3/mole @ 25oC

EPI Suite v.4.11 

calculated from WS and 

VP

Water Solubility 0.4 mg/L

0.39 mg/L @ 25o

C

MRID 42065002

EPI Suite v.4.11

reported value

Octanol – water partition 

coefficient (log KOW)

9.82

6.29 at pH 7.3 and RT

EPI Suite v.4.11

Assessment Report1

Dissociation Constant

(pKa and/or pKb) Not available Not available

Air-water partition 

coefficient (KAW)

KAW = Cair/Cwater = HLC/RT

KAW = 4.09 x 10-5

‘Slightly volatile from a water surface’

Calculated Value,

USEPA, 2008a

Octanol-air partition 

coefficient (KOA) Henry's Law Constant

K RT

K

K

K OW

AW

OW

OA = =

KOA = 1.7 x 1014

Calculated value, using 

KOW 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 Report1

Cwater+soil/Cair

Cwater+soil/Cair = (1/KAW) (1/r + Kd) =

2.0 x 1010

‘Non-volatile from moist soil’

Assuming Kd ≈ KF

Calculated value

USEPA, 2008a

1. Assessment Report published by the EU dated 06/21/2007 (rapporteur state Norway).

2. The structure of the chemical was obtained from the difethialone data sheet available at 

http://www.alanwood.net/pesticides/difethialone.html (accessed 08/26/2015).

Table 3. Summary of Difethialone Environmental Fate Properties

Study Value and unit Degradates MRID or 

Source

Study Classification 

or Comments

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-life1 = 

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 Comments

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 solidwater 

distribution 

coefficient (KF)

KF, 1/n, soil texture (series)

7.7 x 105, 1.89, MS clay (Sharkey)

5.6 x 105

, 1.98, MD sand (Sassafras)

1.8 x 106

, 2.30, MD sandy clay loam

(Sequatchie)

1.6 x 105

, 1.80, CA sandy loam

(Hesperia)

Mean value = 8.2 x 105

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 solidwater organic 

carbon 

normalized

distribution 

coefficient 

(KFOC)

KFOC, 1/n, soil texture (series)

6.2 x 108, 1.89, MS clay (Sharkey)

1.0 x 108

, 1.98, MD sand (Sassafras)

5.3 x 109

, 2.30, MD sandy clay loam 

(Sequatchie)

2.7 x 108

, 1.80, CA sandy loam 

(Hesperia)

Mean value = 1.57 x 109

Bioconcentration

Factor (BCF) 

Steady State BCF=

log BCF = 2.74

(BCF = 555 L/Kg wet-wt)

Biotransformation t1/2 = 4.66 x 103

days (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 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 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-2H-1-benzothiopyran-2-one) is a slightly soluble 

compound (solubility of 0.39 mg/L at 250C) and non-volatile (vapor pressure of 5.55 x 10-7 mmHg 

at 250C; calculated Henry’s Law Constant of 1.00 x 10-6 atm-m3/mole). The compound is 

relatively stable to hydrolysis (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 in 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 the 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. Furthermore, 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 KOW value of 9.82 (EPIWEB v.4.11 estimate), 

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 KF ≈ 8.2 x 

105; mean KFOC ≈ 1.6 x 109) 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 not 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 studies. 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 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 toxicity 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 carcasses 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 fish1

Acute

(99.5%)

Rainbow Trout,

Oncorhynchus mykiss

96 Hr LC50 = 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 EC50 = 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,Cyprinodon variegatus

No data available

Estuarine/marin

e invertebrates

Acute Eastern Oyster,

Crassostrea virginica No data available

Acute Mysid shrimp 

Americamysis bahia 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)

Birds1

Acute

(96 % ai)

Bobwhite quail,

Colinus 

virginianus

30 D LD50 = 

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 LC50 = 

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)

LD50 = 0.55 

mg/kg of bw

40268903/ 

42687704

Acute OralDifethialone/

Fipronil TEP 

Laboratory rat 

(Rattus norvegicus)

LD50 = >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 poisoned 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 these 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 Surrogate Species Toxicological Observations Source (Classification)

Birds1

Non-guideline 

with technical 

grade ai

Black-Billed 

Magpies, Pica pica

Dietary-fed on rodent carcasses 

33 day LC50 = 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 

LC50 = 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 after capture.

6.2 Ecological Incidents

The Ecological Incident Information System (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 magnitude 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 involving 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 observations such as hemorrhaging. 

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 generation 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 the 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 black 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, potential 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 KOW =

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. Similarly, 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 organisms 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 systems, 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 in 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 studies. 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 at sublethal levels and it appears unlikely that major (≥10% AR) metabolites would be formed 

in animal tissues.

8.1.2 Drinking Water 

As 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 potential 

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 the bait (0.0025%), small 

amount applied per placement (~0.000026 lb a.i./placement), and the hydrophobic nature of the 

compound (log KOW = 6.29), leaching of dissolved difethialone from the bait would be so small 

that the potential for contaminating surface 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 

Exposure 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 expected to be lethal to 50% of the 

individuals in the population (i.e., LD50 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 LC50 studies for birds and 14-day LC50 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 mammals 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 Exposure 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 time 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 within 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 the liver half-lives to 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 commonly 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, difethialone 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 t1/2a

(days)

Liver 

retentiona,b

(days)

Reference 

(MRID, if available)

Mouse 20 μg/mouse 1 38.9 28.5 (t1/2) Vandenbroucke et al. 

2008

Rat 0.50 1 2.3 108 (t1/2)

Belleville 1986 

(42065010)

Lechevin and Poche 

1988

Rat 0.06

4

(at weekly 

intervals)

NA 74 (t1/2) Belleville 1991 

(42065009)

a t1/2 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 KOW = 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. It 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 generally 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 considered. 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 functional 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 November 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 Approaches were 

developed jointly by the agencies in response to the NAS recommendations, and reflect a common 

approach to risk assessment shared by the agencies as a way of addressing scientific differences 

between the EPA and the Services. Details of the joint Interim Approaches are contained in the 

November 1, 2013 white paper, Interim 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 registration 

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. This assessment will allow EPA to focus its 

future evaluations on the types of species where the potential for effects exists, once the scientific 

methods being developed by the agencies have been fully vetted. Once the agencies have fully 

developed and implemented the scientific methods necessary to complete risk assessments for listed 

species and their designated critical habitats, these methods 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 program, visit http://www2.epa.gov/endocrine-disruption.
22

11.0 Preliminary Identification of Data Gaps 

11.1 Environmental Fate

Table 6 identifies 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 nondegraded bait, 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 effects 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 Acute Oral Toxicity – Passerine Species

Smaller passerine 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 sublethal 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 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 one upland game 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 these uses, instructions indicate wire should be

inserted through blocks and securely attached 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 leached from 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 generally required 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 rodenticides 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 or 

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

?

Justification and 

Assumptions EPA Will 

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?

Justification 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?

Justification 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 noobservable-adverse-effects

concentration.

NonguidelineAvian dietary 

toxicity –

secondary 

46656501 Supplemental No --

NonguidelineWild 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?

Justification and 

Assumptions EPA will 

Make in Absence of Data

850.4100 Seedling 

Emergence

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 Vegetative 

Vigor

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 Pesticides, 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#rodenticides

(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 Dissipation. 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/series835-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. United 

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 

EnvironmentalContaminationToxicology.
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 BioLife 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 Technical in 

Bobwhite Quail: Project ID: 87 QC 89. Unpublished study prepared by BioLife 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 study 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 Pharmaceutique. 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 

Agriculture, 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 | 0.7228

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 correction | 0.7000 | 0.7000

Const | | Equation Constant | | 0.2290

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

 Log Kow = 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 Methods)

 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 (Modified 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 | | 122.50

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

 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, aromatic 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 Kow: (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 Sol: 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)

 are 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 (0.101 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 | | 0.2051

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 unitless

 = 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 (Car)(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 Linear 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 Probability) | | 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 | Alkyl substituent on aromatic ring | 0.5771 | 1.7313

MolWt| * | Molecular Weight Parameter | | -7.6608

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

 RESULT | Biowin2 (Non-Linear Biodeg 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 Fast

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

TYPE | NUM | Biowin3 FRAGMENT DESCRIPTION | COEFF | VALUE 

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

Frag | 1 | Aliphatic 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

 (Primary & 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 Biodeg 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 Probability)| | 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 alcohol [-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- [cyclic] | -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

Ready 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 Biowin5 (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 biodegradation 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 (phi):

 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/molecule-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 base-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 (Pesticide 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 | Aliphatic 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 | Tetralin | 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 Constant): 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 trophic) = 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 biotransformation 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) 539.49 

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 removal 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 Input/Output Summary

Table 1. Inputs 

Parameter Value

Chemical name Difethialone

Solubility (in water at 25oC; mg/L) 0.39

Mammalian LD50 (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 LD50 (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-Apr2003)

.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-Oct1995)

.0025

7173-223 DIFETHIALONE 0.125% 

LIQUID CONCENTRATE

LIPHATECH, 

INC.

Active -

Conditionally 

Registered (13-Mar1998)

.125

7173-224 DIFETHIALONE 0.5% DRY 

CONCENTRATE

LIPHATECH, 

INC.

Active -

Conditionally 

Registered (07-Jun1999)

.5

7173-226 GENERATION BLOCK LIPHATECH, 

INC.

Active -

Conditionally 

Registered (08-May2003)

.0025

7173-229 GENERATION BLUE 

PELLETS

LIPHATECH, 

INC.

Active -

Conditionally 

Registered (31-Oct2003)

.0025

7173-231

DIFETHIALONE 0.125% 

LIQUID CONCENTRATE 

WITH DENATONIUM 

BENZOATE

LIPHATECH, 

INC.

Active -

Conditionally 

Registered (20-Feb2004)

.125

7173-238 GENERATION MEAL LIPHATECH, 

INC.

Active - Registered 

(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-Aug2007)

.0025

7173-288 DIFETHIALONE BLOCK 

0707 LIPHATECH, INC.

Active - Conditionally 

Registered (22-Oct2009)

.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