# 2 

# REGISTRATION REVIEW

PROBLEM FORMULATION

______________________________________________________________________________



# Zoxamide

CAS Number 156052-68-5

US EPA PC CODE 101702

Prepared by:

Robin Sternberg, Ph.D., Wildlife Biologist

Faruque Khan, Ph.D., Senior Fate Scientist

Environmental Risk Branch 1

Reviewed by:

Meghan Radtke, Ph.D., Acting RAPL

He Zhong, Ph.D., Biologist

Environmental Risk Branch 1 U.S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch I

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

# 3 

# 1 Executive Summary

The Environmental Fate and Effects Division (E FED) has completed the preliminary problem

formulation for the ecological risk, environmenta l fate, endangered species, and drinking water

assessments to be conducted as part of the Re gistration Review of zoxamide. The problem

formulation describes the methods planned to be used during the completion of drinking water

and ecological risk assessments in support of Re gistration Review and provides an overview of

the environmental fate, ecological effects, and potential risks associat ed with the use of

zoxamide as well as uncertainties unique to ri sk assessment of zoxamide. This document also

identifies additional studies that would be be neficial to the conduct of an ecological risk

assessment.

Major findings include the fo llowing data needs and the unc ertainty described below:

 Guideline 835.4100 – Aerobic soil me tabolism, two soils (TGAI);

 Guideline 835.4400 – Anaerobic aquatic metabolism (TGAI);

 Guideline 850.1735 – Whole sediment acute toxici ty invertebrates, fr eshwater (TGAI);

 Guideline 850.1740 – Whole sediment acute toxi city invertebrates, marine (TGAI);

 Guideline 850.2100 – Avian acute oral toxicity test, pa sserine (TGAI);

 Guideline 850.4100 – Seedling emergence and seedling growth, corn and ryegrass

(TEP) 1 

# ; and

 Non-guideline acute larval honey bee feeding study (TGAI).

Justifications for these data needs as well as as sumptions that will be made in the absence of

these data are provided in Section 11

.

The lack of environmental fate and toxicity data for the major degradates of zoxamide ( i.e. , RH150721, RH-24549, RH-141288, RH-129151, RH-139432, RH-127450, and RH-163353) is an

uncertainty in this assessment. In the absence of toxicity data for the degr adates, the stressors of

concern for aquatic organisms are zoxa mide and degradates RH-127450, RH-129151, RH141288, and RH-163353, and a conservative method of considering the stressors of concern in

total, i.e. , total toxic residue (TTR) approach, will be used. These degradates are considered

stressors of concern based on the results of toxicity modeling and/or their st ructural similarity to

zoxamide.



# 2 Introduction

Zoxamide is a non-systemic broad-spectrum ben zamide fungicide. Zoxa mide’s mechanism of

action involves binding at selectiv e sites along the beta subunits of tubulin which results in the

arrest of cell division.

1 

# The submitted study is classified as “s upplemental” because a definitive NOAEC ( i.e. , NOAEC < 1.3 lb

zoxamide/A) could not be determined for corn, and there was a 25% effect on ryegrass dry weight. For corn, a

study that defines a NOAEC ( i.e. , a concentration that is not statistically different from the negative control for all

assessed endpoints) is recommended. For ryegrass, a Tier II seedling emergence test is recommended.

# 4 EFED evaluated the most recent ecological risk assessments for zoxamide in association with

updated toxicity, exposure, and usage information to determine if sufficient data are available

and if further updates are needed to support Re gistration Review. Recent risk assessments by

EFED include a 2001 assessment in support of a S ection 3 registration reque st for use on grapes

and potatoes (DP 266174 and 254295) and a 2013 assessment in support of a Section 3

registration request for use on oni ons (dry bulb), garlic, and sh allots (DP 411544). In addition,

EFED considered the latest Agency science policies and risk assessm ent methodologies.



# 3 Use Characterization

Zoxamide is a non-systemic, broad-spectrum ben zamide fungicide used to control fungicidal

diseases ( e.g. , spot, downy mildew, rot, blight, mold, a nd blotch) on select fruit and vegetable

crops. It is registered for use on cucurb it vegetables (melons, pumpkin, squash, and

watermelon), grapes, potatoes (white/Irish), and tomatoes. The proposed new use of zoxamide

on onions (dry bulb), garlic, and sh allots is currently under review by the Agency. Zoxamide is

formulated as water dispersible granules (dry flowable). Treatment equipment includes aircraft,

sprayer (ground, handheld), and sp rinkler irrigation/system. Th e chemical profile produced by

Biological and Economic Analysis Division (BEAD), located in the docket, lists the use patterns

of maximum exposures (based on pounds of active ingredient appl ied) for the current uses of

zoxamide. EFED will use application scenarios that result in maximum exposure scenarios for a

given use for the risk assessment (see Appendix A for summary of labels).



# 4 Conclusions from Previous Risk Assessments

4.1 Ecological Risk Assessments

EFED has conducted ecological risk assessments on zoxamide that serve as a basis for this

problem formulation, including a 2001 assessment in support of a Section 3 registration request

for use on grapes and potatoes (DP 266174 and 254295) and a 2013 assessment in support of a

Section 3 registration request fo r use on onions (dry bulb), garlic, and shallots (DP 411544). The

results of the 2001 assessment indicated that us e of zoxamide on grapes and potatoes may cause

direct effects to listed freshwater fish and estuar ine/marine invertebrates. The results of the 2013

assessment indicated that the use of zoxamide on onions (dry bulb), garlic, and shallots may

cause direct effects to:

 listed freshwater fish from acute exposure and listed and non-listed fr eshwater fish from

chronic exposure;

 listed estuarine/marine invertebrates from acute exposure and listed and non-listed

estuarine/marine invertebra tes from chronic exposure;

 listed benthic invertebrate s from acute exposure;

 listed aquatic vascular plants and listed and non-listed aqua tic non-vascular plants; and

 listed terrestrial monocots.

It should be noted that risk quotients (RQs) for aquatic organisms in the 2001 assessment were

calculated using EECs for parent zoxamide onl y, even though EECs for zoxamide plus seven

major degradates (RH-150721, RH-24549, RH-141288, RH-129151, RH-139432, RH-127450,

and RH-163353) were presented in the assessment. In contrast, RQs for aquatic organisms in the

# 5 2013 assessment were calculated using EECs ba sed on the total toxic residues (TTR) of

zoxamide (parent zoxamide and selected degradation products including RH-150721, RH141288, RH-127450, and RH-163353).

The following data gaps were id entified in the 2013 assessment:

 Guideline 835.4100 – Aerobic so il metabolism, two soils;

 Guideline 835.4400 – Anaerobic aquatic metabolism;

 Guideline 850.4100 – Seedling emergence and seedling growth, Tier II, corn and

ryegrass;

 Guideline 850.2100 – Avian acute oral toxicity test, passerine;

 Guideline 850.1735 – Whole sediment acute t oxicity invertebrate s, freshwater;

 Guideline 850.1740 – Whole sediment acute toxicity invertebrates, marine; and

 Non-guideline acute honey b ee larvae feeding study.

4.2 Drinking Water Exposure Assessments

The most recent drinking water exposure assessment for zoxamide was conducted in 2014 for the

proposed new use on onions (dry bulb), garl ic, and shallots (DP 417061). Recommended

estimated drinking water concentrations (EDWCs) for currently labeled uses were modeled for

zoxamide (parent only) and the total toxic residues ( TTR) of zoxamide – parent zoxamide and

selected degradation products incl uding RH-150721, RH-24549, RH-141288, RH-129151 and

RH-139432 – as recommended by the Metabolism Assessment Review Committee (DP 270797)

and are provided in Table 4-1

.

Table 4-1. Recommended Estimated Drinking Water Concentrations (EDWCs) Based on

Parent and Total Toxic Residues of Zoxamide (DP 417061)

Drinking Water

Source Crop Scenario Peak Exposure

(μg/L) Annual Mean

Exposure

(μg/L) Average Annual

Exposure

(μg/L)

Zoxamide (Parent only)

Surface water NY Grape STD

Scenario 1 

# 17.55 2.49 0.91

Ground water FL Citrus Scenario 2 

# 1.83E-03 NA 6.84E-04

Total Toxic Residue (Parent +RH-150721, RH-24549, RH-141288, RH-129151 and RH-139432)

Surface water NY Grape STD

Scenario 1 

# 81.3 54.48 22.84

Ground water WI corn Scenario 2 

# 83.5 NA 65.8

1 

# Reported EDWCs generated using PRZM/EXAMS model for aerial application (US EPA 2000) and these values

are revised with recommended cu rrent PCA factor of 0.91.

2 

# Highest EDWCs generated using PRZM-GW model based on 1.60 lbs a.i./A for grape and potato [Gavel 80 WP

(EPA Reg. No.10163-6413)]



# 4.3 Clean Water Act Programs

Zoxamide is not identified as a cause of impairment for any wa ter bodies listed as impaired

under section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) criteria

have been developed for zoxamide. Aquatic be nchmarks have been established for zoxamide

and are available at http://www.epa.gov/oppefed1/ecoris k_ders/aquatic_life_benchmark.htm

.

# 6 Any data submitted or otherwise located as part of the Registration Review process may be used

to update aquatic life benchmar ks if applicable.



# 5 Environmental Fate and Transport

Zoxamide ([ RS ]-3,5-dichloro- N -(3-chloro-1-ethyl-1-methyl-2- oxopropyl)-p-toluamide), a broadspectrum benzamide fungicide, comprises equa l quantities of two enantiomers, but the Senantiomer is the biologically active component of zoxamide. Physical, chemical and

environmental fate properties of zoxamide are presented in Table 5-1 . Zoxamide has a relatively

low vapor pressure (<1.0 x 10 -07 

# mm Hg) and Henry’s Law constant (3.26 x 10 -11 

# atm·m 3 

# /mol),

which suggest that volatilization is not expected to be a major route of dissipation from soil and

water.

Based on registrant-submitted data, zoxamide a ppears to be relatively non-persistent and

moderately mobile to slightly mobile under normal use conditions. The major routes of

dissipation for zoxamide are hydrolysis, photodegr adation in water, and microbial-mediated

degradation in soil and water. Hydrolysis is an important degr adation process for zoxamide, and

the calculated half-lives of zoxamide were 15.5, 15.7 and 8.1 days for pH 4, pH 7 and pH 9,

respectively. Four major transforma tion products (RH-150721, RH-24549, RH-141288 and RH129151) were identified. The photodegradation half- life for zoxamide in water was 15.7 days in

a pH 4 buffer solution, but photodegradation of zoxamide on soil (DT 50 

# of 79 days) does not

appear to be a major route of dissipation. Several major degradates (RH-150721, RH-24549,

RH-139432, RH-129151 and RH-127450) were identified in aqueous and soil photolysis studies.

Zoxamide is also susceptible to microbial-med iated transformation in aquatic and terrestrial

environments. Zoxamide degraded with half -lives of 37.5 and 38.1 days in an aerobic soil

metabolism study and with a DT 50 

# of 14.6 days in an anaerobic soil metabolism study. No major

degradates were observed in aerobic soil metabo lism studies. However, two major degradates

(RH-24549 and RH-127450) were identified in th e anaerobic soil metabolism study. Soil bound

residues accounted for 39 to 56% of the applied radioa ctivity in these studies. Data also suggest

that zoxamide is rapidly transformed in wate r/sediment systems under aerobic conditions (DT 50s 

# of 3.6 to 7.6 days). Several major degradates (RH-24549, RH-127450 and RH-163353) were

identified in an aerobic aquatic metabolism st udy. Sediment-bound residues also accounted for

37% of the applied radio activity in this study. Field dissipation studies show that zoxamide

dissipates with half-lives less th an 69 days. Degradates were not monitored in field dissipation

studies. The maximum percent formation of majo r degradates in various media are listed in

Appendix B

.

Zoxamide is moderately mobile to slightly mobile (K

oc 

# of 815 to 1385 L/Kg) according to the

FAO classification of mobility in soil (FAO, 2000). Given its high affinity for soil and sediment,

zoxamide has the potential to move off the s ite of application duri ng rainfall/irrigation by

erosion/runoff on soil particles and by dr ift during application in the field.

# 7 Table 5-1. Physical, Chemical and Envi ronmental Fate Prop erties of Zoxamide

Property Value Source & Study

Classification

Common name Zoxamide MRID 44731802

Acceptable

CAS Registry No. 156052-68-5

PC Code 101702

Chemical name (CAS) 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-

oxopropyl)-4-m ethylbenzamide

SMILES notation C1=C(C(=O)NC (C(CCl)=O)(CC)C)C=C(C(=C1C

l)C)Cl EPI Suite, v3.12

SMILES

IUPAC name ( RS )-3,5-dichloro- N -(3-chloro-1-ethyl-1-methyl-2-

oxopropyl)-p-toluamide TOXNET

Synonyms RH-117281 and RH-7281

Structure TOXNET

Molecular formula C 14 

# H 16 

# Cl 3 

# NO 2 

# TOXNET

Physical and Chemical Properties

Molecular weight 336.1 TOXNET

Physical state Fine po wder MRID 4431803

Acceptable

Vapor pressure <1.33.5 x 10 -5 

# Pa (25 o 

# C)

<1.0 x 10 -7 

# mm Hg (25 o 

# C) MRID 4431803

Acceptable

Henry’s Law constant 3.26 x 10 -11 

# atm x m 3 

# /mol MRID 46515901

Acceptable

Specific gravity/density 1.38g/cm 3 

# @ 20 o 

# C MRID 44731803

Acceptable

Solubility in water 0.681 mg/L @ 25 o 

# C

55.7 g/L in acetone @ 2 o 

# C

20.0 Ethyl acetate @ 25 o 

# C

6.49 g/L in n-octanol

0.038 g/L in n-heptane MRID 44731803

Acceptable

# 8 Property Value Source & Study

Classification

log K

ow 

# 3.76 ±0.04 (25 o 

# C) MRID 44731803

Acceptable

Laboratory accumulation in fish

bioaccumulation factor (BCF)

( Lepomis macrochirus )

A depuration half-life 30x in edible tissues

360x non-edible (viscera) tissues

180x for whole body

464-1670x (lipid adjusted BCF values)

< 1 day MRID 44731932

Acceptable

Environmental Fate Properties

Hydrolysis half-life

pH = 5

pH = 7

pH = 9 15.5 days

15.7 days

8.1 days

Major Degradates

RH-150721 (Max 37.6% @ day 21; pH 4.0)

RH -24549 (Max 30.9% @ day 30; pH 4.0)

RH-141288 (Max 50.2% @ day 30; pH 9.0)

RH-129151 (Max 24.5% @ day 21; pH 7.0) MRID 44731908

Acceptable

Photolysis half-life in water 15.7 days (when the pH 4 hydrolysis DT 50 

# of 15.5

days was used instead of dark control)

Major Degradates

RH-150721 (Max 15.1% @ day 10)

RH -24549 (Max 27.7% @ day 30)

RH-139432 (Max 42.4% @ day 30) MRID 44731911

Acceptable

Photolysis half-life in soil 79 days

Major Degradates

RH -24549 (Max 22.2% @ day 30)

RH-127450 (Max 10.9% @ day 14) MRID 44731910

Acceptable

Aerobic soil metabolism half-life 38.1 days (loamy sand)

37.5 days (silt loam)

No major degradates were detected.

Minor Degradates

RH-127450 (Max 6%)

RH-129151 (Max <2%)

RH-139432 (Max 1%)

RH-24549 (Max 7%)

Maximum bound residue 39% MRID 44731912

MRID 44731913

Acceptable

Anaerobic soil metabolism half-life 14.6 days (sandy loam soil)

Major degradates

RH -24549 (Max 16.87% @ day 59) MRID 44731914

Acceptable

# 9 Property Value Source & Study

Classification

RH-127450 (Max 13.45% @ day 59)

Minor Degradates

RH-141288 (Max <1%)

RH-141452 (Max <1.0%)

RH-129151 (Max <1.0%)

RH-139432 (Max <1%)

Maximum bound residue 56%

Aerobic aquatic metabolism half-life

for total system 3.6 days (Rhine River) @ 20°C

7.6 days (Judenweiher pond) @ 20°C

Major Degradates in total system

RH-127450 (Max 30.1% @ day 28; Rhine River)

RH -163353 (Max % 20.6 @ day 56; in Rhine

River)

Maximum bound residue 39% MRID 44770002

Acceptable

Anaerobic aquatic metabolis m half-life No data

Soil adsorption coefficient

K

oc 

# (L/kg) Adsorption

K

d 

# (L/kg)

3.4 loam

10.3(sandy loam)

12.4 (silty clay)

15.2 (sandy loan)

25.3 (silty loam)

K

oc 

# (L/kg)

815 loam

1196(sandy loam)

1294 (silty clay)

1385 (sandy loam)

1431 (silty loam)

Desorption

K

d 

# (L/kg)

4.2 loam

11.78(sandy loam)

10.73 (silty)

15.56 (sandy loan)

29.57 (silty loam)

K

oc 

# (L/kg)

927 loam

1032(sandy loam)

1618(silty)

1671 (sandy loam)

1671 (silty loam) MRID 44731916

Acceptable

Terrestrial field dissipation half-life Bare soils multiple applications

11.5 days in Madera, CA (multiple applications) MRID 44732127

Supplemental

# 10 Property Value Source & Study

Classification

17.7 days in Lyons, NY (multiple applications)

15 days in Lyons, NY (single application)

9.4 days in Minto, Manitoba

14.2 days in Branchton, Ontario

68.6 days in Hunter River, Prince Edward Island

Major Degradates

Since no major degradates were detected in the

aerobic soil metabolism study, transformation

products of zoxamide were not monitored. MRID 44732126

Supplemental



# 6 Receptors

6.1 Zoxamide

Summaries of the most sensitive toxicity data us ed to characterize the to xicity of zoxamide to

terrestrial and aquatic or ganisms are provided in Table 6-1 . Summaries of all submitted toxicity

data for zoxamide can be found in Appendix C

.

For parent zoxamide, there are no data available for acute oral toxicity to a passerine species,

acute dietary (oral) toxicity to larval honey b ees, and toxicity to benthic invertebrates.

Based on available data, zoxamide is practica lly non-toxic to birds on acute oral and subacute/dietary bases; practically non-toxic to mammals on an acute oral basis; practically nontoxic to adult honey bees on an acute contact and oral bases; up to highly toxic to freshwater fish

on an acute basis; practically non-toxic up to the lim it of solubility to estuarine/marine fish on an

acute basis; at most highly toxi c to freshwater invertebrates on an acute basis; and very highly

toxic to estuarine/marine inve rtebrates on an acute basis.

It should be noted that acute to xicity data with a formulation of zoxamide and mancozeb are

available for freshwater fish, fr eshwater invertebrates, and aquatic non-vascular plants. These

acute toxicity endpoints expresse d in terms of zoxamide concen trations can be compared to

zoxamide (parent only) peak EECs from spray drift alone to assess risk from exposure to

zoxamide as a result of a mixture of zoxamide and mancozeb directly entering a water body via

spray drift.11Table 6-1. Summary of Most Sensitive Endpoints from Toxicity Studies with Zoxamide(Synonyms: RH-117,281; RH-141,455;RH-7281) and Zoxamide Co-Formulated with MancozebStudy TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationAvian acute oral:single dose, 14-dayobservationRH-117,281Technical(92.9)Bobwhite quail(Colinus virginianus)LD50> 2000 mg a.i./kg-bw (nom)NOAEL = 2000 mg a.i./kg-bw (nom)(no mortality or sublethal effects)Practically non-toxicMRID 44731933AcceptableNA Passerine species No data NAAvian sub-acutedietary: 5-dayexposure; 3-daypost-exposureobservationRH-117,281Technical(92.9)Mallard duck(Anas platyrhynchos)LC50> 5250 mg a.i./kg-diet (nom)NOAEC = 2625 mg a.i./kg-diet (nom)LOAEC = 5250 mg a.i./kg-diet (nom)(NOAEC based on 10% mortality at 5250 mg/kg-diet; nosublethal effects)Practically non-toxicMRID 44731935AcceptableAvian reproduction:22 weeks(chronic)RH-117,281Technical(92.3)Bobwhite quail(Colinus virginianus)Mallard duck(Anas platyrhynchos)NOAEC = 1000 mg a.i./kg-diet (nom)LOAEC >1000 mg a.i./kg-diet (nom)(no effects)MRIDs 44731936& 44947401AcceptableMammalian acuteoral limit: singledose; 14-dayobservationRH-141,455(98.74)Rat(Rattus norvegicus)LD50> 5,000 mg a.i./kg-bwNOAEL: not determined(no mortality; scant feces in allmales and females on day 1 and 2females on day 2)Practically non-toxicMRID 44731837AcceptableMammalian 2-generationreproduction(chronic)RH-117,281Technical(92.3)Rat(Rattus norvegicus)Parental, systemic toxicityNOAEC = 5,000 mg a.i./kg-diet (409.3 mg a.i./kg-bw/day)LOAEC = 20,000 mg a.i./kg-diet (1624.4 mg a.i./kg-bw/day)(based on decreased weights and body weight gains in femalesonly)Reproductive toxicityNOAEC≥20,000 mg a.i./kg-diet (2091.2/2239.1 [M/F] mga.i./kg-bw/day)(based on no effects)MRID 44770001Acceptable12Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationBee acute contact:single dose, 48-hourobservationRH-117,281Technical(>95)Adult honey bee(Apis mellifera)LD50> 100 μg a.i./bee (nom)NOAEL = 100 μg a.i./bee (nom)(1-3% mortality across solvent control and 4 treatmentconcentrations)Practically non-toxicMRID 44731919AcceptableBee acute oral limit:72 hoursForm.:Dithane/RH7281 DG BlendMancozeb(69)Zoxamide(8.26)Adult honey bee(Apis mellifera)LD50> 12.6 μg zoxamide/bee#NOAEL = 12.6 μg zoxamide/bee#LD50> 106 μg mancozeb/bee#NOAEL = 106 μg mancozeb/bee#LD50>153 μg form./beeNOAEL = 153 μg form./bee(0 and 23% mortality in the solvent control and 153 μg form./beetreatment groups, respectively)Practically non-toxicMRID 44950504AcceptableLarval bee acutedietary (oral)NA Larval bee No data NATerrestrial plantseedling emergence:Tier I (limit), 21daysTEP: Gavel®75DFMancozeb(64)Zoxamide(8.7)Most sensitivemonocots: Ryegrass andcornCorn (based on height)EC25> 1.3 lb zoxamide/ANOAEC < 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC < 10.7 lb mancozeb/ARyegrass (based on dry weight)EC25= ~1.3 lb zoxamide/ANOAEC: Not determinedaEC25= ~10.7 lb mancozeb/ANOAEC: Not determinedaMRID 49183404Supplemental(due to the lack ofa definitiveNOAEC for cornheight and a 25%effect on ryegrassdry weight)Most sensitive dicot:NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/A13Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationNOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneTerrestrial plantvegetative vigor:Tier I (limit), 21daysTEP: Gavel®75DFMancozeb(64)Zoxamide(8.7)Most sensitive monocot:NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneMRID 49183405AcceptableMost sensitive dicot:NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneFreshwater fishacute: 96 hours,flow-throughRH-117,281Technical(94.2)Rainbow trout(Oncorhynchus mykiss)LC50(95% C.I.) = 156 (134-181) μg a.i./L (mm)Probit slope (95% C.I.) = 6.4 (3.9-8.9)NOAEC = 51 μg a.i./L (mm)LOAEC = 140 μg a.i./L (mm)(NOAEC based on signs of toxicity including quiescence,surfacing, dark discoloration, labored respiration, and lying on thebottom at≥140 μg/L)Highly toxicMRID 44731926AcceptableForm.:Dithane/ RH7281 80 WPMancozeb(71.00)Zoxamide(7.09)Rainbow trout(Oncorhynchus mykiss)Preliminary endpointsLC50(95% C.I.) = 10 (8-13) μg zoxamide/L (mm)NOAEC = 2 μg zoxamide/L (mm)LOAEC = 6 μg zoxamide/L (mm)LC50(95% C.I.) = 120 (76-176) μg mancozeb/L (mm)NOAEC = 3 μg mancozeb /L (mm)LOAEC = 6.3 μg mancozeb /L (mm)LC50(95% C.I.) = 159 (129-232) μg form./L (mm)NOAEC = 87 μg form./L (mm)LOAEC = 92 μg form./L (mm)MRID 46056401In review14Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassification(NOAEC based on mortality and signs of toxicity including slightdark coloration, slight lethargy, and near base of tank at 92 μgform./L)Freshwater fish earlylife stage: 61 days,flow-through(chronic)RH-117,281Technical(92.9)14C-RH-117,281(98.7)Rainbow trout(Oncorhynchus mykiss)NOAEC = 3.48 μg a.i./LLOAEC = 6.87 μg a.i./L(based on reduction in fry survival at 35 and 61 days post-hatch)MRID 44731929AcceptableEstuarine/marinefish acute: 96 hours,flow-throughRH-117,281Technical(92.3)Sheepshead Minnow(Cyprinodon variegatus)LC50> 860 μg a.i./L (mm)NOAEC = 860 μg a.i./L (mm)(no mortality or sublethal effects up to solubility,i.e., 860 μg/L)Practically non-toxic up to the limit of solubilityMRID 44731928AcceptableEstuarine/marinefish early life stage:28 days, flowthrough(chronic)RH-117,281Technical(92.3)Sheepshead Minnow(Cyprinodon variegatus)NOAEC = 40 μg a.i./L (mm)LOAEC = 78 μg a.i./L (mm)(based on a reduction in wet weight)MRID 44731930AcceptableFreshwaterinvertebrate acute:48 hours, flowthroughRH-117,281Technical(94.2)Water flea(Daphnia magna)EC50> 780 μg a.i./L (mm)NOAEC = 780 μg a.i./L (mm)(no immobility or sublethal effects; precipitate at highestconcentration, considered to be the solubility limit under theconditions of this test)No more than highly toxicMRID 44731920AcceptableForm.:Dithane/RH117,281 75 DGBlendMancozeb(69)Zoxamide(8.26)Water flea(Daphnia magna)EC50(95% C.I.) = 306 (228-400) μg RH-7281 /L (mm)Probit slope (95% C.I.) = 3.6 (2.0-5.3)NOAEC = 78.3 μg zoxamide /L (mm)LOAEC = 122 μg zoxamide/L (mm)EC50(95% C.I.) = 2690 (2020-3580) μg mancozeb/L (mm)Probit slope (95% C.I.) = 3.5 (1.9-5.0)NOAEC = 558 μg mancozeb /L (mm)LOAEC = 1190 μg mancozeb /L (mm)EC50(95% C.I.) = 3800 (3000-5000) μg form./L (mm)MRID 44950502Acceptable15Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationProbit slope (95% C.I.) = 3.8 (3.0-5.0)NOAEC = 820 μg form./L (mm)LOAEC = 1700 μg form./L (mm)(NOAEC based on mortality and the sublethal effect of lying onthe bottom of the test chamber at≥1700 μg form./L)Freshwaterinvertebrate lifecycle: 21 days, flowthrough (chronic)RH-117,281Technical(92.3)Water flea(Daphnia magna)21-day NOAEC = 39 μg a.i./L (mm)21-day LOAEC = 74 μg a.i./L (mm)(NOAEC based reduction in parental survival at≥74 μg/L)MRID 44731921AcceptableEstuarine/marineinvertebrate acute:96 hours, flowthroughRH-117,281Technical(92.3)Mysid shrimp(Mysidopsis bahia)LC50(95% C.I.) = 76 (67-87) μg a.i./L (mm)Probit slope (95% C.I.) = 9.0 (5.2-12.9)NOAEC = 17 μg a.i./L (mm)LOAEC = 31 μg a.i./L (mm)(NOAEC based on sublethal effect of erratic swimming at≥31μg/L; lethargy at 132 μg/L – the highest treatment concentration)Very highly toxicMRID 44731923AcceptableEstuarine/marineinvertebrate lifecycle: 27 days, flowthrough (chronic)RH-117,281Technical(92.3)14C-RH-7281(96.3)Mysid shrimp(Mysidopsis bahia)NOAEC = 7.2 μg a.i./L (mm)LOAEC = 14 μg a.i./L (mm)(NOAEC based on a reduction in reproduction and growth [lengthand weight])MRID 44731925AcceptableBenthic invertebrate NA NA No data NAAquatic vascularplant: 14 days, staticrenewalRH-117,281Technical(92.3)14C-RH-7281Technical(96.3)Duckweed(Lemna gibba)EC50(95% C.I.) = 19 (16-27) μg a.i./L (mm)NOAEC = 9.0 μg a.i./L (mm)LOAEC = 18 μg a.i./L (mm)(NOAEC based on reduction in frond number; smaller-thannormal root size at three highest concentrations)MRID 44731945AcceptableAquatic nonvascular plant:96 hours, staticRH-117,281Technical (92.3)14C-RH-117,281(96.3)Green alga(Scenedesmussubspicatus)EC50(95% C.I.) = 10 (7.8-13) μg a.i./L (mm)NOAEC = 7.0 μg a.i./L (mm)LOAEC = 14 μg a.i./L (mm)(NOAEC based on reduction in cell density;clumping/flocculation and cellular enlargement at≥14 μg a.i./L)MRID 44731939Supplemental(due to testspecies)16Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationForm.:Dithane/RH117,281 DGBlendMancozeb(69)Zoxamide(8.26)Green alga(Selenastrumcapricornutum)EC50(95% C.I.) = 1.95 (1.52-2.51) μg RH-7281 /L (TWA)NOAEC = 0.584 μg zoxamide /L (TWA)LOAEC = 1.16 μg zoxamide/L (TWA)EC50(95% C.I.) = 9.42 (7.38-12) μg mancozeb/L (TWA)NOAEC = 2.68 μg mancozeb /L (TWA)LOAEC = 5.17 μg mancozeb /L (TWA)EC50(95% C.I.) = 11.4 (8.91-14.2) μg form./L (TWA)NOAEC = 3.26 μg form./L (TWA)LOAEC = 6.33 μg form./L (TWA)(based on reduction in cell density)MRID 44950501AcceptableAbbreviations: C.I. = confidence interval; form. = formulation; im = initial measured; mm = mean measured; nom = nominal; NA =not applicable; NS = notspecified; TEP = typicalend-use product; TWA = time-weighted average#Endpoint calculated by multiplying the concentrationin μg form./bee (as reported) by the % a.i.aGiven the 25% effect on dry weight, the power of thetest was deemed insufficient for determining a NOAEC.

# 17 6.2 Degradates

There are no toxicity data available for any of the seven major degradates of zoxamide ( i.e. , RH24549, RH-127450, RH-129151, RH-139432, RH-141288, RH-150721, and RH-163353).

Degradates RH-127450, RH-141288, and RH-163353 c ontain a 3,5-dichloro-4-methylbenzamide

core structure similar to parent zoxamide ( Table 6-2 ), and degradate RH-129151 is expected to

be interconvertible with a chemical that c ontains a 3,5-dichloro-4-methylbenzamide core

structure. In contrast, RH-150721, RH-139432, and RH-24549 are not structurally similar to

parent zoxamide (see Table 6-2 ). EPI Suite: ECOSAR analyses indicate that degradates RH127450 and RH-141288 may be equally or only slightly less toxic ( e.g. , <10x) to aquatic

organisms than zoxamide ( Table 6-2 ). Therefore, in the absen ce of toxicity data for the

degradates, the stressors of concern for aquati c organisms are zoxamide and degradates RH127450, RH-129151, RH-141288, and RH-163353, and a cons ervative method of considering

the stressors of concern in total, i.e. , total toxic residue (TTR) appr oach, will be used. It should

be noted that in the 2013 ecologi cal risk assessment in support of a Section 3 registration request

for use on onions (dry bulb), garlic, and shallo ts (DP 411544), parent zoxamide and degradates

RH-150721, RH-141288, RH-127450, and RH-163353 were in cluded in the TTR of zoxamide.

However, a further review of the degradate structures and results of EPI Suite: ECOSAR

modeling during the problem formulation stage of Registration Review indicated that RH129151 should be added to the TTR of zoxamide and that RH-150721 should be excluded from

the TTR of zoxamide.18Table 6-2. Results of EPI Suite: ECOSAR Modeling for Zoxamide and Its Major DegradatesChemicalStructureTaxonObservedEPI Suite: ECOSAR ClassIncluded in Total ToxicResidues (TTR) of Zoxamide?RationaleAmidesHaloKetonesHaloBenzamidesAliphaticAminesEstersNeutralOrganicsa-b KetoneAlcoholsAcute/Chronic Endpoints (mg/L)ZoxamideFish0.156/0.000350.6/0.0040.01/0.0042.02/0.107YesParentDaphnid>0.780/0.0390.761/0.010.702/0.015Greenalgae0.010.164/0.5620.206/0.041RH-127450Fish0.855/0.0052.73/0.15YesStructurally similar to parent;both have 3,5-dichloro-4-methylbenzamide coreToxicity predicted to be equalto parentDaphnid0.993/0.013Greenalgae0.173/0.505RH-141288Fish2.44/0.0146.91/0.4125.3/0.22YesStructurally similar to parent;both have 3,5-dichloro-4-methylbenzamide coreToxicity predicted to be onlyslightly less toxic than parentDaphnid2.35/0.0317.08/0.967Greenalgae0.259/0.53211.1/3.86RH-163353Fish23.59/0.13951.35/3.66YesStructurally similar to parent;both have 3,5-dichloro-4-methylbenzamide coreDaphnid14.87/0.196Greenalgae0.592/0.555RH-129151Fish0.749/1.04YesExpected to beinterconvertible with achemical that contains a 3,5-dichloro-4-methylbenzamidecore (parent has a 3,5-dichloro-4-methylbenzamidecore)Daphnid0.792/0.094Greenalgae0.642/0.116RH-150721Fish4.95/0.0994.32/2.50NoNot structurally similar toparent;parent is a benzamidewhereas RH-150721 is abenzoateDaphnid0.717/0.02545.1/0.255Greenalgae0.543/0.1357.09/2.8519ChemicalStructureTaxonObservedEPI Suite: ECOSAR ClassIncluded in Total ToxicResidues (TTR) of Zoxamide?RationaleAmidesHaloKetonesHaloBenzamidesAliphaticAminesEstersNeutralOrganicsa-b KetoneAlcoholsAcute/Chronic Endpoints (mg/L)RH-139432Fish9.23/0.05521.19/1.46NoNot structurally similar toparent; RH-139432 has atruncated amide chainDaphnid6.34/0.084Greenalgae0.31/0.341RH-24549Fish49.4/5.77NoNot structurally similar toparent; parent is a benzamidewhereas RH-24549 is abenzoic acidDaphnid35.9/5.45Greenalgae35.8/18.2

# 20 6.3 Ecological Incidents

The ecological incident information system (EIIS ) is an OPP database that houses ecological

incidents that have been repor ted to the Agency. When ava ilable, EIIS includes date and

location of an incident, type and magnitude of effects observed in vari ous species, use(s) of

pesticides known or suspected of contributing to the inci dent, and results of any chemical residue

analysis or other analyses conducted during in cident investigation. EIIS incidents are

categorized according to the certai nty that the incident resulted from pesticide exposure. The

Avian Monitoring System (AIMS) is a database administered by the Amer ican Bird Conservancy

that contains publicly available data on reported avian incidents involving pesticides. Many of

the incidents listed in this data base are also in the EIIS.

Reviews of the EIIS (version 2.1.1) and AIMS on March 5, 2014 did not yield any reported

ecological incidents associated with the use of zoxamide.

In addition to the incidents reco rded in EIIS and AIMS, additiona l incidents are reported to the

Agency in aggregated form. Pesticide registrant s report certain types of incidents to the Agency

as aggregate counts of incidents occurring per product pe r quarter. Ecologi cal incidents reported

in aggregate reports include thos e categorized as ‘minor fish a nd wildlife’, ‘minor plant’, and

‘other non-target’ incidents. ‘Other non-target’ incidents include reports of adverse effects to

insects and other terrestrial invert ebrates. For zoxamide, registra nts have not reported any minor

incidents as of March 5, 2014.

The total number of actual incide nts associated with the use of zoxamide may be higher than

what is reported to the Agency. Incident s may go unreported since effects may not be

immediately apparent and/or readil y attributed to the use of a ch emical. Therefore, a lack of

reported incidents should not be taken as an indicator of little or no ecological risk.



# 7 Exposure Pathways of Concern

The environmental fate properties and use patterns of zoxamide indicate that direct spray, spray

drift, leaching to ground water, and runoff represent potential tran sport mechanisms of zoxamide

to aquatic and terrestrial organisms.

Drinking water and inhalation e xposure pathways were screen ed using the SIP (Screening

Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods and were

found to be exposure pathways of low con cern (no LOC exceedances are expected; see

Appendix D ). SIP and STIR are described in detail at:

http://www.epa.gov/oppefed1/ models/terrestrial/index.htm

.



# 8 Analysis Plan

8.1 Stressors of Concern

8.1.1 Ecological Risk Assessment

# 21 The stressors of concern for aquatic organi sms are zoxamide and degradates RH-127450, RH129151, RH-141288, and RH-163353. These degradates are considered stre ssors of concern

based on the results of EPI Suite: ECOSAR toxicity modeling and/or their stru ctural similarity to

zoxamide ( Table 6-2 ).

The stressor of ecological concern for terrestrial organisms is zoxamide.

8.1.2 Drinking Water Exposure Assessment

A new drinking water assessment may be conducte d, if warranted, to support future human

health dietary risk assessments of zoxamide fo r all currently register ed uses. The drinking

assessments of zoxamide incorporat e zoxamide residues of concern ( i.e. , RH-150721, RH24549, RH-141288, RH-129151 and RH-139432) as recommended by the Metabolism

Assessment Review Committee (MARC) of the Health Effects Divisi on (DP 270797) in surface

and ground waters. The zoxamide residues of c oncern may be reevaluated pending receipt and

review of additional environmental fate and toxicity data for zoxamide and its degradates.

8.2 Measures of Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and

terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

.

A TTR approach will be used to estimate exposure to aquatic organisms. Degradates RH127450, RH-129151, RH-141288, and RH-163353 will be in cluded in the TTR of zoxamide

based on the results of EPI Suite: ECOSAR toxicity modeling and/or their stru ctural similarity to

zoxamide ( Table 6-2 ).

8.2.1 Available Monitoring Data

The Agency is aware of monitoring conducted by federal and state agenci es and this route of

exposure will be considered in the assessment to th e extent that data on zoxamide are available.

8.3 Measures of Effect

Toxicity data presented in Section 6 of this problem formulation w ill be used to calculate risk

quotients. Any additional information submitted by th e registrant or found in the open literature

prior to conducting the risk assessment will also be considered. The open literature studies are

identified using EPA’s ECOTOXicology database (ECOTOX) 2 

# 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 provi de insight into the direct and indirect effects

of pesticides on biotic communities from loss of species that are sensitiv e to the chemicals and

from changes in structure and functional ch aracteristics of the affected communities.

2 

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

# 22 

# 9 Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the

Agency will evaluate risks to federally listed th reatened and/or endangere d (listed) species from

registered uses of zoxamide during Registrati on Review. The process for evaluating potential

risks to listed species is further described at

http://www.epa.gov/oppfead1/enda nger/litstatus/riskasses.htm

.



# 10 Endocrine Disruptors Screening Program

Zoxamide was not included in th e first group of 67 chemicals for which an order was issued to

conduct Tier 1 EDSP testing. For additional information the EDSP program, visit

http://www.epa.gov/endo/

.



# 11 Preliminary Identification of Data Gaps

11.1 Environmental Fate

Table 11-1 identifies environmental fate studies that offer data for each guideline requirement

and whether or not further data are needed in order to support risk assessment. There are no

environmental fate studies available for a ny of the major degradates of zoxamide ( i.e. , RH150721, RH-24549, RH-141288, RH-129151, RH-139432, RH -127450, and RH-163353). In the

absence of environmental fate data for these degr adates, a TTR approach will be used to estimate

exposure to aquatic organisms. De gradates RH-127450, RH-129151, RH-141288, and RH163353 will be included in the TTR of zoxamide base d on their structural similarity to zoxamide

and results of EPI Suite modeling. The EPI (Estimation Programs Interface) SuiteTM is a

Windows ® 

# -based suite of physical/chemical prope rty and environmental fate estimation

programs developed by the EPA’s Office of Polluti on Prevention Toxics and Syracuse Research

Corporation (SRC). Additional environmental fate and physicochemical properties of major

degradates can reduce the uncerta inties in the aquatic exposure and drinking water assessments.

Table 11-1. Submitted Environmental Fate Data for Zoxamide

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

835.2120 Hydrolysis 4473 1909 Acceptable No --

835.2240 Aqueous

photolysis 44731911 Acceptable No --

835.2410 Soil photolysis 4 4731910 Acceptable No --

# 23 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

835.4100 Aerobic soil

metabolism 44731912

44731913 Acceptable

Acceptable Yes

Partially

fulfilled OCSPP guidance recommends that

these tests be performed with four

soils. Two aerobic soil metabolism

studies have already been submitted

and classified as acceptable for risk

assessment. An additional two

studies are required under 40 CFR

Part 158 for terrestrial outdoor uses.

Because OCSPP uses an upper 90 th



# percentile estimate of soil

metabolism half-lives based on

available study data for modeling

purposes, any additional data can

reduce uncertainty related to the

exposure assessment as well as the

half-life value used in modeling.

835.4200 Anaerobic soil

metabolism 44731914 Acceptable No

Partially

fulfilled OCSPP guidance recommends that

these tests be performed with four

soils. One anaerobic soil metabolism

study has already been submitted

and is classified as acceptable for

risk assessment. Additional data are

required under 40 CFR Part 158 for

terrestrial outdoor uses. Additional

data are considered to have a low

potential to add value to exposure

assessments for the ecological risk

and drinking water in presence of

anaerobic aquatic metabolism

(835.4400).

835.4300 Aerobic aquatic

metabolism 44770002 Acceptable No --

835.4400 Anaerobic

aquatic

metabolism No data NA Yes Data are required under 40 CFR Part

158. OCSPP guidance recommends

that these tests be performed with

two sediments. The assumption of

compound stability will be made in

the absence of acceptable data.

835.1230

835.1240 Adsorption/

desorption and

leaching 44731916 Acceptable No --

835.1410 Volatility –

laboratory No data NA No Zoxamide is not expected to be

volatile under normal use conditions

based on low vapor pressure and

Henry’s Law Constant

835.6100 Terrestrial field

dissipation 44732126 Supplemental No ---

44732127 Supplemental

# 24 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

850-6100 Analytical

method in soil 44731906 Supplemental No ---

Analytical

method in water 44731908 Supplemental

165-4

(850.1730) Fish

bioconcentration 4731932 Accepta ble No ---

NA = not applicable



# 11.2 Ecological Effects

Tables 11-2 and 11-3 identify ecological effects studies th at offer data for each guideline

requirement and whether or not fu rther data are needed in order to support risk assessment.

There are no ecological effects studies available for any of the major degradates of zoxamide

( i.e. , RH-150721, RH-24549, RH-141288, RH-129151, RH-139432, RH-127450, and RH163353). In the absence of toxicity data for these degradates, the stressors of concern for aquatic

organisms are zoxamide and degrad ates RH-127450, RH-129151, RH-141288, and RH-163353,

and a conservative method of considering the stressors of concern in total, i.e. , the total toxic

residue (TTR) approach, will be used.25Table 11-2. Submitted Aquatic Ecological Effects Data for ZoxamideOCSPPGuidelineDataRequirementSourceMRIDClassificationAre DataNeeded toConduct theRiskAssessment?Justification and Assumptions EPA Will Make in the Absence of Data850.1010 Freshwaterinvertebrateacute toxicity44731920 Acceptable No --850.1025850.1035850.1045850.1055Saltwaterinvertebrateacute toxicity44731924(mollusk)Acceptable No --44731923(mysid)Acceptable850.1075 Freshwater fishacute toxicity44731926(cold water)Acceptable No --44731931(warm water)Acceptable44731927(warm water)Acceptable850.1075 Saltwater fishacute toxicity44731928 Acceptable No --850.1300 Freshwaterinvertebratelife cycle44731921 Acceptable No --850.1350 Saltwaterinvertebrateslife cycle44731925 Acceptable No --850.1400 Freshwater fishearly-life stage44731929 Acceptable No--850.1400 Saltwater fishearly-life stage44731930 Acceptable No --850.1500 Fish life cycle,freshwater44731931 Acceptable No850.1735850.1740Wholesediment:acuteinvertebratesfreshwaterand marineNo data NA YesAcute sediment invertebrate toxicity data are required under 40 CFR Part 158 if:i.the half-life of the pesticide in sediment if≤10 days in either the aerobic soilor aquatic metabolism studies and if any of the following exist:A.The soil partition coefficient (Kd) is≥50B.The log Kow is≥3.C.The Koc is≥1,000.26OCSPPGuidelineDataRequirementSourceMRIDClassificationAre DataNeeded toConduct theRiskAssessment?Justification and Assumptions EPA Will Make in the Absence of DataThe half-life of zoxamide in aerobic aquatic metabolism studies ranges from 3.6to 7.6 days; the log Kow of zoxamide is 3.76; and zoxamide Koc’s in silty loamand sandy loam are all≥1196.Acute sediment tests with the midgeChironomus dilutus, freshwater amphipodHyalella azteca, and/or estuarine/marine amphipodLeptocheirus plumulosusareneeded.In the absence of these data, sediment-dwelling invertebrate acute toxicity data forsurrogate pesticides – starting with data for closely related pesticides andproceeding to data for less related pesticides – may be used to characterize thechronic toxicity of zoxamide to sediment-dwelling invertebrates.850.4400 Aquatic planttoxicity testusingLemnaspp.44731945 Acceptable No --850.4500 Algal toxicity 4473193844731939(green alga)AcceptableSupplementalNo --44731942(marinediatom)Acceptable44770005(freshwaterdiatom)Acceptable850.4550 Cyanobacteriatoxicity44731940 Acceptable No --NA = not applicable27Table 11-3. Submitted Terrestrial Ecological Effects Data for ZoxamideOCSPPGuidelineDataRequirementSourceMRIDClassificationAre DataNeeded toConduct theRiskAssessment?Justification and Assumptions EPA Will Make in the Absence of Data850.2100 Avian oraltoxicity44731933(upland game)Acceptable No Acute oral toxicity data for a passerine speciesare required under the new 40CFR Part 158. A study has not been submitted for this data requirement.A guideline-compliant passerine acute oraltoxicity test is needed. Acute oraltoxicity data are only available for one avian species (i.e., bobwhite quail).Passerine birds may utilize metabolic pathways that are different from largerbirds and therefore be more sensitive to zoxamide. Furthermore, passerinesexhibit behavioral responses to pesticide dosing that are potential indicators ofreduced fitness in the field (e.g., regurgitation of contaminated diet) even whendirect biochemically-mediated lethal toxicity is not apparent.In the absence of these data, passerine toxicity data for surrogate pesticides –starting with data for closely related pesticides and proceeding to data for lessrelated pesticides – may be used to characterize the acute toxicity of zoxamideto passerine species.No data(passerine)NA Yes850.2200 Avian dietarytoxicity44731934(upland game)Acceptable No --44731935(waterfowl)Acceptable850.2300 Avianreproduction44731936(upland game)Acceptable No --44947401(waterfowl)Acceptable850.3020 Honey bee acutecontact toxicity44731919 Acceptable No --NonguidelineHoney bee acuteoral toxicity44950504 Acceptable No28OCSPPGuidelineDataRequirementSourceMRIDClassificationAre DataNeeded toConduct theRiskAssessment?Justification and Assumptions EPA Will Make in the Absence of DataNonguidelineLarval honeybee acute oraltoxicityNo data NA YesThe “White Paper in Support of the Proposed Risk Assessment Process forBees” as submitted to the FIFRA Scientific Advisory Panel3proposes ascreening-level risk assessment processthat includes acute contact and oraltoxicity tests with adult bees and an acute oral toxicity test with larval bees.Larval honey bee acute oral toxicity data are not available.In the absence of these data, larval honey bee oral toxicity data for surrogatepesticides – starting with data for closely related pesticides and proceeding todata for less related pesticides – may be used to characterize the oral toxicity ofzoxamide to honey bees.850.4100 SeedlingEmergence andSeedlingGrowth49183404Supplemental YesAcceptable data are not available.The submitted study isclassified as“supplemental” because a definitive NOAEC (i.e., NOAEC < 1.3 lbzoxamide/A) could not be determined for corn, and there was a 25% effect onryegrass dry weight. For corn, a study that defines a NOAEC (i.e., aconcentration that is not statistically different from the negative control for allassessed endpoints) is recommended. For ryegrass, a Tier II seedlingemergence test is recommended.850.4150 VegetativeVigor49183405 Acceptable No --NA = not applicable3http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0543-0004

# 29 

# 12 References

DP 266174 and 254295. Section 3 Registration Request for Uses of Zoxamide. January 3, 2001.

DP 270797. PP#9F05058; Zoxamide in/on Potato and Grapes. Conclusions of the 11/14/2000

Meeting of the Metabolism A ssessment Review Committee.

DP 411544. Zoxamide: Ecological Risk Assessment to Support the Proposed New Uses on

Onions (Dry Bulb), Garlic, and Shallots. December 23, 2013.

DP 417061. Drinking Water Exposure Assessment in Support of the New Use Registration of

Zoxamide Formulated Product Gavel® 75DF on On ions (Dry Bulb), Garlic and Shallots.

January 17, 2014.

FAO 2000. Food and Agriculture Organization of the United Nations. FAO PESTICIDE

DISPOSAL SERIES 8. Assessing Soil Contamin ation: A Reference Manual. Appendix 2.

Parameters of pesticides th at influence processes in the soil. Editorial Group, FAO

Information Division: Rome, 2000.

http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm

Cited Environmental Fate Studies

44731802 Kemmerer, S.; Roemmele, R. (1998) Product Chemistry Series 830 Group A,

Guideline Numbers OPPTS: 830.1550, 830.1600, 830.1620, 830.1670, 830.1700,

830.1750, 830.1800: Product Identity, Composition, and Analysis for RH117,281 Technical: Lab Project Number : APR-98-282: TM-98-212-02: APR-98-

277. Unpublished study prepared by Rohm and Haas Company and Lancaster

Laboratories. 481 p.

44731906 Szuter, S.; Guo, I. (1998) Independent Laboratory Method Vali dation Trials RH117,281 Analytical Method Soil (TR 34- 98-126): Lab Project Number: 1401.15:

34-98-160: TR 34-98-126. Unpublished study prepared by Mckenzie

Laboratories, Inc. 101 p. {OPPTS 850.7100}

44731907 Vlkel, W. (1998) Analytical Method for the Determination of RH-117281 in

Drinking Water: Lab Project Numb er: 1401.36: 692256: 34P-98-24. Unpublished

study prepared by RCC, Ltd. 35 p.

44731908 Reynolds, J. (1998) Hydrolysis of (c arbon-14) RH-117281 in Water at pH 4, 7,

and 9: Lab Project Number: XBL95006: RPT00251: 34P-95-20. Unpublished

study prepared by Xenobiotic Laboratories, Inc. 349 p.

44731910 Reynolds, J. (1997) Soil Photolysis of (carbon-14)RH-117281: Lab Project

Number: 95009: RPT00261: 34-P-95-74. U npublished study prepared by Agvise

Laboratories and Xenobiotic La boratories, Inc. 138 p.

# 30 44731911 Reynolds, J.; Smalley, J. (1998) Aqueous Photolysis of (carbon-14)RH-117281:

Lab Project Number: XBL95008: RPT00259: 34-96-215. Unpublished study

prepared by Xenobiotic La boratories, Inc. 146 p.

44731912 Reynolds, J.; Smalley, J. (1997) Aer obic Soil Metabolism of (carbon-14)RH117281 Fungicide: Lab Project Numb er: XBL95003: RPT00256: 34P-95-10.

Unpublished study prepared by Xenobiot ic Laboratories, Inc. 193 p.

44731913 Carbone, J. (1998) Deviation of Degr adation Kinetics of RH-117,281 Technical

Fungicide for PRZM3.12 Modeling Further An alysis of Data from Aerobic Soil

Metabolism of (carbon-14)-RH-117,281 Fungi cide: Lab Project Number: 98R1101. Unpublished study prepared by Rohm and Haas Company. 24 p.

44731914 Kang, H. (1997) Anaerobic Soil Me tabolism of (carbon-14)RH-117281: Lab

Project Number: XBL95010: RPT00267: 34P-95-75. Unpublished study prepared

by Rohm and Haas Company and XenoB iotic Laboratories, Inc. 123 p.

44731916 Shelby, D. (1996) Adsorption and Desorption of RH-117,281 to Soil: Lab Project

Number: 6627-95-0224-EF-001: 95-0024: TR34-96-01. Unpublished study

prepared by Ricerca, Inc. 105 p.

44732126 Vaughn, F. (1998) Dissipation of RH-7281 on Soil in Canada: Lab Project

Number: 97RHC01: 97RHC 01-A: 98RHC33.REP. Unpublished study prepared

by Enviro-Quest, and Vaughn Agricultura l Research Services, Ltd. 262 p.

44732127 Ross, J. (1998) Terrestrial Field Dissipation of RH-117,281 on Bare Soil in

California and New York: Lab Project Number: 34P-96-30: 34P-96-30A: 34P-96-

30-B. Unpublished study prepared by Grayson Research LLC, and Rohm and

Haas Company. 658 p.

44731932 Robinson, R. (1998) RH-117,281: Uptake , Depuration, Bioconcentration and

Metabolism of (carbon-14)-RH-117,281 in Bl uegill Sunfish Under Flow Through

Test Conditions: Lab Project Numb er: XBL96025: RPT00328: 34P-96-26.

Unpublished study prepared by Xenobiot ic Laboratories, Inc. and ABC

Laboratories, Inc. 345 p.

44770002 Morgenroth, U. (1998) (Carbon-14)-RH- 117281: Degradation and Metabolism in

Aquatic Systems: Lab Project Nu mber: TR34-98-47: 624510: 34P-96-42.

Unpublished study prepared by RCC Ltd. 121 p.

Cited Ecological Effects Studies

44731919 Kirkland, R. (1993) Acute Contact Toxi city of RH-117,281 Technical to Honey

Bees: Lab Project Number: BIO 109-93: 92RC-0235. Unpublished study prepared

by Rohm and Haas Company and Bio Research. 55 p.

44731920 Sword, M. (1995) Acute Flow-Through T oxicity of RH-117,281 Technical to

Daphnia magna : Lab Project Number: 94RC-0081: 41683: 94P-081. Unpublished

study prepared by ABC Laboratories, Inc. 268 p.

# 31 44731921 Stewart, S.; Murrell, H.; Rhodes, J. (1997) Chronic Toxicity of RH-117,281

Technical to Daphnia magna Under Flow-Through Test Conditions: Lab Project

Number: 43209: 95RC-0273. Unpublished study prepared by ABC Laboratories,

Inc. 79 p.

44731922 Van der Kolk, J. (1998) RH-117,281: Chronic Effects on Midge Larvae

( Chironomus riparius ) in a Water/Sediment System: Final Report: Lab Project

Number: 97RC-0083: 97-063-1007: 1007.027.173. Unpublished study prepared by

Springborn Laboratories. 85 p.

44731923 Roberts, C.; Swigert, J. (1997) RH-117,281 Technical: A 96-Hour Flow-Through

Acute Toxicity Test with the Saltwater Mysid ( Mysidopsis bahia ): Final Report:

Lab Project Number: 129A-136: 95RC-0275: SDR23. Unpublished study prepared

by Wildlife International Ltd. 89 p.

44731924 Roberts, C.; Swigert, J. (1997) RH -117,281 Technical: A 96-Hour Shell Deposition

Test with the Eastern Oyster ( Crassostrea virginica ): Final Report: Lab Project

Number: SDR23: 129A-137: 95RC-0276. Unpub lished study prepared by Wildlife

International Ltd. 93 p.

44731925 Drottar, K.; Krueger, H. (1998) RH-117,281 Technical: A Flow- Through LifeCycle Toxicity Test with the Saltwater Mysid ( Mysidopsis bahia ): Final Report:

Lab Project Number: 1294-142: 97RC- 0077. Unpublished study prepared by

Wildlife International Ltd. 152 p.

44731926 Sword, M.; Gardner, C. (1995) Acute Flow-Through Toxicity of RH-117,281

Technical to Rainbow Trout ( Oncorhynchus mykiss ): Final Report: Lab Project

Number: 94RC0078: 41681. Unpublished study prepared by ABC Laboratories,

Inc. 254 p.

44731927 Sword, M.; Gardner, C. (1995) Acut e Flow-Through Toxicity of RH-117,281

Technical to Bluegill ( Lepomis macrochirus ): Final Report: La b Project Number:

94RC-0080: 41682. Unpublished study prepared by ABC Laboratories, Inc. 227 p.

44731928 Roberts, C.; Swigert, J. (1997) RH-117,281 Technical: A 96-Hour Flow-Through

Acute Toxicity Test with the Sheepshead Minnow ( Cyprinodon Variegatus ): Final

Report: Lab Project Number: 129A-135: 95RC-0274. Unpublished study prepared

by Wildlife International, Ltd. 90 p.

44731929 Downing, J.; Leak, T.; Stewart, S. (1996) Early Life-Stage of RH-117281

Technical to the Rainbow Trout ( Oncorhynchus mykiss ) Under Flow-Through

Conditions: Lab Project Number: 42400: 94RC-0239. Unpublished study prepared

by ABC Laboratories, Inc. 490 p.

44731930 Drottar, K.; Krueger, H. (1998) RH -117,281 Technical: An Early Life-Stage

Toxicity Test with the Sheepshead Minnow ( Cyprinodon variegatus ): Final Report:

Lab Project Number: 129A-143A: 97 RC-0078. Unpublished study prepared by

Wildlife International, Ltd. 142 p.

# 32 44731931 Drottar, K.; Krueger, H. (1998) RH-117,281 Technical: A Flow-Through LifeCycle Toxicity Test with the Fathead Minnow ( Pimephales promelas ): Final

Report: Lab Project Number: 129A-141: 97RC-0079. Unpublished study prepared

by Wildlife International, Ltd. 188 p.

44731933 Williams, B. (1997) RH-117,281 Technical : 14-Day Acute Oral LD50 Study in

Bobwhite Quail: Lab Project Number: RH117BWLD-595: 94RC-0240.

Unpublished study prepared by Ecological Planning and Toxicology, Inc. 44 p.

44731934 Williams, B. (1997) RH-117,281 Technical : 8-Day Acute Dietary LC50 Study in

Bobwhite Quail: Lab Project Number: RH117BWLC-395: 94RC-0242.

Unpublished study prepared by Ecological Planning and Toxicology, Inc. 94 p.

44731935 Williams, B. (1997) RH-117,281 Technical : 8-Day Acute Dietary LC50 Study in

Mallard Ducklings: Lab Projec t Number: RH117MDLC-395: 94RC-0241.

Unpublished study prepared by Ecological Planning and Toxicology, Inc. 94 p.

44731936 Kapustka, L. (1998) Avian Reproducti on Study of RH-117,281 Technical with

Northern Bobwhite: Lab Projec t Number: 97RC-0081: RH7281BW-97-2.

Unpublished study prepared by Ecological Planning and Toxicology, Inc. 288 p.

44731938 Ziegler, T.; Stewart, S. (1996) Ac ute Toxicity of RH-117,281 Technical to

Selenastrum capricornutum Printz: Lab Project Number: 42399: 94RC-0238.

Unpublished study prepared by A BC Laboratories, Inc. 438 p.

44731939 Drottar, K.; Sutherland, C.; Krueger, H. (1998) RH-117,281 Technical: A 96-Hour

Toxicity Test with the Freshwater Alga ( Scenedesmus subspicatus ): Lab Project

Number: 129A-151: 97RC-0133. Unpublis hed study prepared by Wildlife

International Ltd. 91 p. {OPPTS 850.5400}

44731940 Drottar, K.; Sutherland, C.; Krueger, H. (1998) RH-117,281 Technical: A 96-Hour

Toxicity Test with the Freshwater Alga ( Anabaena flos-aquae ): Lab Project

Number: 129A-154: 97RC-0130. Unpublis hed study prepared by Wildlife

International Ltd. 85 p.

44731942 Drottar, K.; Krueger, H. (1998) RH- 117,281 Technical: A 96-Hour Toxicity Test

with the Marine Diatom ( Skeletonema costatum ): Final Report: Lab Project

Number: 129A-152: 97RC-0132. Unpublis hed study prepared by Wildlife

International Ltd. 84 p. {OPPTS 850.5400}

44731945 Drottar, K.; Krueger, H. (1998) RH -117,281 Technical: A 14-Day Static-Renewal

Toxicity Test with Duckweed ( Lemna gibba G3): Final Report: Lab Project

Number: 129A-147: 97RC-0080. Unpublis hed study prepared by Wildlife

International Ltd. 86 p. {OPPTS 850.4400}

44770003 Downing, J.; Leak, T. (1995) RH-117, 281 T echnical: Toxicity to the Earthworm,

Eisenia foetida : Lab Project Number: 94RC-0237: 42398-6. Unpublished study

prepared by ABC Laboratories, Inc. 256 p.

44770005 Drottar, K.; Sutherland, C.; Krueger, H. (1998) RH-117, 281 Technical: A 96-Hour

Toxicity Test with th e Freshwater Diatom ( Navicula pelliculosa ): Final Report: Lab

# 33 Project Number: 97RC-0131: 129A-153: C.3. Unpublished study prepared by

Wildlife International Ltd. 89 p. {OPPTS 850.5400}

44947401 Gallagher, S.; Beavers, J.; Martin, K. et al. (1999) RH -117,281 Technical: A

Reproduction Study with the Mallard ( Anas platyrhynchos ): Lab Project Number:

98RC-0166: 129-164. Unpublished study prepared by Rohm and Haas Company.

220 p.

44950501 Ward, C.; Murdock, C. (1998) Toxic ity of Dithane/RH-117,281 DG Blend to

Selenastrum capricornutum Printz: Lab Project Number: 44178: 97RC-0069.

Unpublished study prepared by A BC Laboratories, Inc. 181 p.

44950502 Madsen, T.; Leak, T. (1998) Acute T oxicity of Dithane/RH-117,281 DG Blend to

Daphnia magna : Lab Project Number: 44179-97: 97RC-0068. Unpublished study

prepared by ABC Laboratories, Inc. 79 p.

44950503 Rhodes, J.; Bucksath, J. (1998) Acute Flow-Through Toxicity of Dithane/RH117,281 DG Blend to Rainbow Trout ( Oncorhynchus mykiss ): Lab Project Number:

43357: 97RC-0128: 95P-278. Unpublished study prepared by ABC Laboratories,

Inc. 110 p.

44950504 Milligan, D. (1997) Dithane/RH-117,281 DG Blend (8:1): Laboratory Oral and

Contact Test with the Honeybee, Apis mellifera : Final Report: Lab Project Number:

97-071-1007: 97RC-0070: 1007.030.265. Unpublished study prepared by

Springborn Laboratories AG. 48 p.

46056401 Dickson, J.; Knight, B. (1998) Dithane/ RH-7281 80 EP (10:1): Determination of

Acute Toxicity (LC50) to Rainbow Trout (96h, Continuous Flow). Project Number:

16697, 97RC/0214, 392008. Unpublished study prepar ed by Inveresk Research. 42

p.

46056403 Rhodes, J. (1999) Acute Toxicity of Dithane/RH-7281 (11.2:1) DG Blend to the

Green Alga, Selenastrum capricornutum . Project Number: 45118, 98RC/0238.

Unpublished study prepared by Analytical Bio-Chemistry Labs., Inc. 156 p.

46096901 Buchanan, J.; Knight, B.; Dickson, J. (1998) Dithane/RH-7281 80WP (10:1):

Determination of Acute Toxicity (EC50) to Daphnia (48h, Continuous Flow).

Project Number: 16564, 97RC/0215, 392029. Unpublished study prepared by

Inveresk Research International. 42 p.

49183404 Sindermann AB, Porch JR, Krueger HO, Martin KH and R VanHoven. 2012. Gavel

(Mancozeb 66.7%, Zoxamide 8.3%): A Tier I to xicity test to determine the effects

of the test substance on s eedling emergence of ten speci es of plants. Unpublished

study performed by Wildlife International, Ltd., Easton, Maryland. Laboratory

project no.: 334-126. Study sponsored by Go wan Company, Yuma, Arizona. Study

initiated July 11, 2011 and completed January 19, 2012.

49183405 Sindermann AB, Porch JR, Krueger HO, Martin KH and R VanHoven. 2011. Gavel

(Mancozeb 66.7%, Zoxamide 8.3%): A Tier I to xicity test to determine the effects

of the test substance on vegetative vigor of ten species of pl ants. Unpublished study

# 34 performed by Wildlife Inte rnational, Ltd., Easton, Ma ryland. Laboratory project

no.: 334-127. Study sponsored by Gowa n Company, Yuma, Arizona. Study

initiated July 11, 2011 and completed December 12, 2011.35Appendix A: Summary of Zoxamide LabelsCropEPAReg #ProductNameMax.SingleApp.Rate(lb a.i./A)Max. #App./CropCycleMax.SeasonalApp.Rate/CropCycle(lb a.i./A)Min.App.Interval(days)App.TimingApplicationEquipment/TypeDisallowedGeographicalAreasAllowableGeographicalAreasCucurbitvegetablesGrapesTomato10163-6413Zoxium80WAgriculturalFungicide0.281.67FoliarSprinkler irrigation/chemigationAircraft/sprayGround/sprayHand heldsprayer/sprayPotato,white/Irish10163-6413Zoxium80WAgriculturalFungicide0.281.65FoliarSprinkler irrigation/chemigationAircraft/sprayGround/sprayHand heldsprayer/sprayGrapes10163-6414Gavel 75 DF0.207530.62257Bloom,pre-bloomAircraft/broadcastGround/broadcastWest of RockyMountainsPost-bloomCAWest of RockyMountainsBloom,post-bloom,pre-bloomSprinklersystem/chemigationWest of RockyMountainsEast of RockyMountainsGrapes10163-6414Gavel 75 DF0.2075610.2457Bloom,pre-bloomAircraft/sprayGround/sprayEast of RockyMountainsPost-bloomCAEast of RockyMountainsPotato,white/irish10163-6414Gavel 75 DF0.16660.9965FoliarAircraft/broadcastFL, RI, DE, ME,CT, VT, NH,NY, MA, MI,WI, OH, PAGround/broadcastFL, NY, PA, VT,DE, NH, RI, CT,OH, MA, ME,WI, MI36CropEPAReg #ProductNameMax.SingleApp.Rate(lb a.i./A)Max. #App./CropCycleMax.SeasonalApp.Rate/CropCycle(lb a.i./A)Min.App.Interval(days)App.TimingApplicationEquipment/TypeDisallowedGeographicalAreasAllowableGeographicalAreasSprinkler irrigation/chemigationDE, MI ,PA,NY, ME, RI,MA, OH, WI,CT, NH, FL,VTME, VT, MI,DE, NY, PA,CT, FL, WI,MA, OH, NH, RIAircraft/sprayOH, NH, RI,FL, CT, WI,ME, MI, DE,PA, NY, VT,MAGround/sprayDE, ME, MI,NY, PA, VT,OH, FL, NH,RI, MA, CT,WITomato10163-6414Gavel 75 DF0.16640.6647FoliarAircraft/broadcastGround/broadcastWest of RockyMountainsSprinklersystem/chemigationWest ofMississippiRiverTomato10163-6414Gavel 75 DF0.16681.3287FoliarSprinkler irrigation/chemigationAircraft/sprayGround/sprayEast ofMississippiRiver37Appendix B: Environmental Transformation Products of ZoxamideTable B-1. Environmental Transformation Products of ZoxamideCode Name/SynonymChemical Name/Smiles CodeChemical StructureStudy Type/Corresponding OCSPPGuidelineMRIDMaximum % AR(interval)1Major (>10%) Transformation ProductsRH-150721(3-amino-3-methyl-2-oxo)pentyl-(3,5-dichloro4-methyl) benzoatec1c(cc(c(c1CL)C)CL)C(=O)OCC(=O)(C(C)(CC)N)Hydrolysis @pH 4835.213044731908 36.7 (21 day)Aquatic Photolysis835.224044731911 15.1 (10 days)RH-245493,5-dichloro-4-methylbenzoic acidc1c(cc(c(c1CL)C)CL)C(=O)OHydrolysis @pH 4835.213044731908 30.9 (10 days)Aquatic Photolysis835.224044731911 27.7 (30 days)Soil Photolysis835.241044731910 22.2 (30 days)Anaerobic Soil Metabolism835.42004431912443191316.9 (59 days)RH-1412883,5-dichloro-N-(3-hydroxy-1-ethyl-1-methyl--2-oxopropyl)-4-methylbenzamidec1c(cc(c(c1CL)C)CL)C(=O)(N(C(C(=O)(CO))(C)CC))Hydrolysis @pH 9835.213044731908 50.2 (30 days)RH-1291512-(3,5-dichloro-4-methylphenyl)-4-ethyl-4-methyl-4H-1,3-oxazin5(6H)-onec1(c(c(cc(c1)C2=NC(C(=O)(CO2))(C)CC)CL)C)CLHydrolysis @pH 7835.213044731908 24.5 (21 days)38Code Name/SynonymChemical Name/Smiles CodeChemical StructureStudy Type/Corresponding OCSPPGuidelineMRIDMaximum % AR(interval)1RH-1394323,5-dichloro-4-methylbenzamidec1c(cc(c(c1CL)C)CL)C(=O)(N)Aquatic Photolysis835.224044731911 42.4 (30 days)RH-1274503,5-dichloro-N-(1-ethyl-1-methyl-2- oxopropyl)-4-methylbenzamidec1c(cc(c(c1CL)C)CL)C(=O)(N(C(C(=O)(C))(C)CC))Soil Photolysis835. 241044731910 10.9 (14) days)Aerobic Aquatic Metabolism835.430044770002 30.1 (28 days)RH-1633533,5-dichloro-N-(2-carboxy1-ethyl-1-methyl-2-oxoethyl)-4-methylbenzamidec1c(cc(c(c1CL)C)CL)C(=O)(N(C(C(=O)(C(=O)(O)))(C)CC))Aerobic Aquatic Metabolism835.430044770002 20.6 (56 days)-- Carbon Dioxide CO2Aerobic Soil Metabolism835.4200447319124473191347.8 (122 days)-- Bound Residue ---Aerobic Soil Metabolism835.4200447319124473191338.4 (122 days)Anaerobic Soil Metabolism835.420044731914 56.4 (30 days)Aerobic Aquatic Metabolism835.430044770002 39.9(56 days)Minor (<10%) Transformation ProductsTransformation Products1 to 610 to 12No Structure and CAS nameavailableSoil Photolysis835. 241044731910 6.73(21 days)2Met 1No Structure and CAS nameavailableAnaerobic Soil Metabolism835.420044731914 0.97 (59 days)Met 2No Structure and CAS nameavailableAerobic Soil Metabolism835.420044731912447319130.57 (30 days)39Code Name/SynonymChemical Name/Smiles CodeChemical StructureStudy Type/Corresponding OCSPPGuidelineMRIDMaximum % AR(interval)1Met 4No Structure and CAS nameavailableAerobic Soil Metabolism835.4200447319124473191312.5 (14 day)3Met 5No Structure and CAS nameavailableAnaerobic Soil Metabolism835.420044731914 0.49 (15 days)Met 6No Structure and CAS nameavailableAnaerobic Soil Metabolism835.420044731914 0.47 (15 days)Met 7No Structure and CAS nameavailableAnaerobic Soil Metabolism835.420044731914 3.83 (0 days)Met 8No Structure and CAS nameavailableAnaerobic Soil Metabolism835.420044731914 4.67 (30 days)1Bold font indicates maximum concentration of degradate observed in various environmental fate studies.2Percent of aggregate of several transformation products3TLCsuggests that Met 4 consisted of between four and six additional transformation products40Appendix C: Summary of ToxicityStudies with Zoxamide and ZoxamideCo-Formulated with MancozebTable C-1. Summary of Endpoints from Toxicity Studieswith Zoxamide (Synonyms:RH 117,281; RH-141,455; RH-141,452;RH- 7281) and Zoxamide Co-Formulated with MancozebStudy TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationAvian acute oral:single dose, 14-dayobservationRH-117,281Technical(92.9)NABobwhite quail(Colinus virginianus)LD50> 2000 mg a.i./kg-bw (nom)NOAEL = 2000 mg a.i./kg-bw (nom)(no mortality or sublethal effects)Practically non-toxicMRID 44731933AcceptableAvian sub-acutedietary: 5-dayexposure; 3-daypost-exposureobservationRH-117,281Technical(92.9)Mallard duck(Anas platyrhynchos)LC50> 5250 mg a.i./kg-diet (nom)NOAEC = 2625 mg a.i./kg-diet (nom)LOAEC = 5250 mg a.i./kg-diet (nom)(NOAEC based on 10% mortality at 5250 mg/kg-diet; no sublethaleffects)Practically non-toxicMRID 44731935AcceptableBobwhite quail(Colinus virginianus)LC50> 5250 mg a.i./kg-diet (nom)NOAEC = 5250 mg a.i./kg-diet (nom)(no mortality; wing droop on day 3 at 5250 mg/kg-diet)Practically non-toxicMRID 44731934AcceptableAvian reproduction:22 weeks(chronic)RH-117,281Technical(92.3)Bobwhite quail(Colinus virginianus)NOAEC = 1000 mg a.i./kg-diet (nom)LOAEC >1000 mg a.i./kg-diet (nom)(no effects)MRID 44731936AcceptableMallard duck(Anas platyrhynchos)NOAEC = 1000 mg a.i./kg-diet (nom)LOAEC >1000 mg a.i./kg-diet (nom)(no effects)MRID 44947401AcceptableMammalian acuteoral limit: singledose; 14-dayobservationRH-141,455(98.74)Rat(Rattus norvegicus)LD50> 5,000 mg a.i./kg-bwNOAEL = not determined(no mortality; scant feces in allmales and females on day 1 and 2females on day 2)Practically non-toxicMRID 44731837AcceptableRH-141,452(97.7)Laboratory Mouse(Mus musculusdomesticus)LD50> 5,000 mg a.i./kg-bwNOAEL = not determined(no treatment-related mortality;scant feces in 1 male on day 1)MRID 44731834Acceptable41Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationPractically non-toxicMammalian 2-generationreproduction(chronic)RH-117,281Technical(92.3)Rat(Rattus norvegicus)Parental, systemic toxicityNOAEC = 5,000 mg a.i./kg-diet(409.3 mg a.i./kg-bw/day)LOAEC = 20,000 mg a.i./kg-diet(1624.4 mg a.i./kg-bw/day)(based on decreased weights and body weight gains in females only)Reproductive toxicityNOAEC≥20,000 mg a.i./kg-diet (2091.2/2239.1 [M/F] mg a.i./kgbw/day)(based on no effects)MRID 44770001AcceptableBee acute contact:single dose, 48-hour observationRH-117,281Technical(>95%)Honey bee(Apis mellifera)LD50> 100 μg a.i./bee (nom)NOAEL = 100 μg a.i./bee (nom)(1-3% mortality across solvent control and 4 treatment concentrations)Practically non-toxicMRID 44731919AcceptableForm.:Dithane/RH7281 DG BlendMancozeb(69)Zoxamide(8.26)Honey bee(Apis mellifera)LD50> 16.52 μg zoxamide /bee#NOAEL = 16.52 zoxamide/bee#LD50> 138 μg mancozeb/bee#NOAEL = 138 μg mancozeb/bee#LD50>200 μg form./beeNOAEL = 200 μg form./bee(3% mortality in the solvent control and 0, 30, 0, 10, and 0% mortalityat 12.5, 25, 50, 100, and 200 μg form./bee)Practically non-toxicMRID 44950504AcceptableBee acute orallimit: 72 hoursForm.:Dithane/RH7281 DG BlendMancozeb(69)Zoxamide(8.26)Honey bee(Apis mellifera)LD50> 12.6 μg zoxamide /bee#NOAEL = 12.6 μg zoxamide/bee#LD50> 106 μg mancozeb/bee#NOAEL = 106 μg mancozeb/bee#LD50>153 μg form./beeNOAEL = 153 μg form./beeMRID 44950504Acceptable42Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassification(0 and 23% mortality in the solvent control and 153 μg form./beetreatment groups, respectively)Practically non-toxicSoil: 14 days RH-117,281Technical(94.2)Earthworm(Eisenia foetida)LC50> 1070 mg a.i./kg-soilNOAEC = 66.7 mg a.i./kg-soilLOAEC = 134 mg a.i./kg-soil(NOAEC based on 20-35% mortality≥134 mg/kg-soil compared to5% mortality at 66.7 mg/kg-soil; also lethargy at≥134 mg/kg-soil)MRID 44770003Supplemental(not a guidelinestudy)Terrestrial plantseedlingemergence: limit,21 daysTEP: Gavel®75DFMancozeb(64)Zoxamide(8.7)Most sensitivemonocots: Ryegrassand cornCorn (based on height)EC25> 1.3 lb zoxamide/ANOAEC < 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC < 10.7 lb mancozeb/ARyegrass (based on dry weight)EC25= ~1.3 lb zoxamide/ANOAEC: Not determinedEC25= ~10.7 lb mancozeb/ANOAEC: Not determinedMRID 49183404Supplemental(due to the lackof a definitiveNOEC for cornheight and a25% effect onryegrass dryweight)Most sensitive dicot:NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneTerrestrial plantvegetative vigor:limit, 21 daysTEP: Gavel®75DFMancozeb(64)Zoxamide(8.7)Most sensitivemonocot: NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneMRID 49183405Acceptable43Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationMost sensitive dicot:NoneEC25> 1.3 lb zoxamide/ANOAEC = 1.3 lb zoxamide/AEC25> 10.7 lb mancozeb/ANOAEC = 10.7 lb mancozeb/AMost sensitive parameter: NoneFreshwater fishacute: 96 hours,flow-throughRH-117,281Technical(94.2)Rainbow trout(Oncorhynchusmykiss)LC50(95% C.I.) = 156 (134-181) μg a.i./L (mm)Probit slope (95% C.I.) = 6.4 (3.9-8.9)NOAEC = 51 μg a.i./L (mm)LOAEC = 140 μg a.i./L (mm)(NOAEC based on signs of toxicityincluding quiescence, surfacing,dark discoloration, labored respiration, and lying on the bottom at≥140 μg/L)Highly toxicMRID 44731926AcceptableForm.: Dithane/RH-7281 80 WPMancozeb(71.00)Zoxamide(7.09)Rainbow trout(Oncorhynchusmykiss)Preliminary endpointsLC50(95% C.I.) = 10 (8-13) μg zoxamide /L (mm)NOAEC = 2 μg zoxamide /L (mm)LOAEC = 6 μg zoxamide /L (mm)LC50(95% C.I.) = 120 (76-176) μg mancozeb/L (mm)NOAEC = 3 μg mancozeb /L (mm)LOAEC = 6.3 μg mancozeb /L (mm)LC50(95% C.I.) = 159 (129-232) μg form./L (mm)NOAEC = 87 μg form./L (mm)LOAEC = 92 μg form./L (mm)(NOAEC based on mortality and signs of toxicity including slight darkcoloration, slight lethargy, and near base of tank at 92 μg form./L)MRID 46056401In reviewRH-117,281TechnicalFathead minnow(Pimephalespromelas)LC50> 208 μg a.i./L (mm)(no mortality)At most highly toxicMRID 44731931AcceptableNOTE:submitted withlife cycle study44Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationRH-117,281Technical(94.2)Bluegill sunfish(Lepomismacrochirus)LC50> 790 μg a.i./L (mm)NOAEC: not specified(0, 20, 0, and 20%≤0.17, 0.29, 0.49, and 0.79 μg/L; signs of toxicityincluding quiescence, surfacing,dark discoloration, laboredrespiration, and lying on the bottom at≥0.17 μg/L; exopthalmia [popeye] at all treatment levels only at 24 hours)At most highly toxicMRID 44731927AcceptableForm.: Dithane/RH-117,281 75DG BlendMancozeb(69)Zoxamide(8.26)Rainbow trout(Oncorhynchusmykiss)LC50(95% C.I.) = 162 (133-198) μg zoxamide /L (mm)Probit slope (95% C.I.) = 5.3 (3.3-7.4)NOAEC = 80 μg zoxamide /L (mm)LOAEC = 163 μg zoxamide /L (mm)LC50(95% C.I.) = 1360 (1130-1600) μg mancozeb/L (mm)Probit slope (95% C.I.) = 6.2 (3.7-8.7)NOAEC = 680 μg mancozeb/L (mm)LOAEC = 1410 μg mancozeb/L (mm)LC50(95% C.I.) = 1900 (1600-2300) μg form./L (mm)Probit slope = 6.0NOAEC = 980 μg form./L (mm)LOAEC = 2000 μg form./L (mm)(NOAEC based on mortality and signs of toxicity including laboredrespiration, quiescence, surfacing, exophthalmia, and lying on thebottom at≥2000 μg form./L)MRID 44950503AcceptableFreshwater fishearly life stage: 61days, flow-through(chronic)RH-117,281Technical(92.9)14C-RH-117281(98.7)Rainbow trout(Oncorhynchusmykiss)NOAEC = 3.48 μg a.i./LLOAEC = 6.87 μg a.i./L(based on reduction in fry survival at 35 and 61 days post-hatch)MRID 44731929AcceptableFreshwater fish lifecycle: 219 days,flow-throughRH-117,281Technical(92.3)14C-RH-117,281(98.50)Fathead minnow(Pimephalespromelas)NOAEC = 60 μg a.i./L (mm)LOAEC = 121 μg a.i./L (mm)(based on F0: reductions in day 32 and day 60 total length and F1:reductions in hatching success and 28-day survival and growth [lengthand weight])MRID 44731931Acceptable45Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassificationEstuarine/marinefish acute: 96 hours,flow-throughRH-117,281Technical(92.3)Sheepshead Minnow(Cyprinodonvariegatus)LC50> 860 μg a.i./L (mm)NOAEC = 860 μg a.i./L (mm)(no mortality or sublethal effects up to solubility,i.e., 860 μg/L)Practically non-toxic up to the limit of solubilityMRID 44731928AcceptableEstuarine/marinefish early life stage:28 days, flowthrough(chronic)RH-117,281Technical(92.3)Sheepshead Minnow(Cyprinodonvariegatus)NOAEC = 40 μg a.i./L (mm)LOAEC = 78 μg a.i./L (mm)(based on a reduction in wet weight)MRID 44731930AcceptableFreshwaterinvertebrate acute:48 hours, flowthroughRH-117,281Technical(94.2)Water flea(Daphnia magna)EC50> 780 μg a.i./L (mm)NOAEC = 780 μg a.i./L (mm)(no immobility or sublethal effects; precipitate at highestconcentration, considered to be the solubility limit under the conditionsof this test)No more than highly toxicMRID 44731920AcceptableForm.:Dithane/RH117,281 75 DGBlendMancozeb(69)Zoxamide(8.26)Water flea(Daphnia magna)EC50(95% C.I.) = 306 (228-400) μg zoxamide /L (mm)Probit slope (95% C.I.) = 3.6 (2.0-5.3)NOAEC = 78.3 μg zoxamide /L (mm)LOAEC = 122 μg zoxamide /L (mm)EC50(95% C.I.) = 2690 (2020-3580) μg mancozeb/L (mm)Probit slope (95% C.I.) = 3.5 (1.9-5.0)NOAEC = 558 μg mancozeb /L (mm)LOAEC = 1190 μg mancozeb /L (mm)EC50(95% C.I.) = 3800 (3000-5000) μg form./L (mm)Probit slope (95% C.I.) = 3.8 (3.0-5.0)NOAEC = 820 μg form./L (mm)LOAEC = 1700 μg form./L (mm)(NOAEC base on mortality and the sublethal effect of lying on thebottom of the test chamber at≥1700 μg form./L)MRID 44950502AcceptableForm.:Dithane/RH7281 80WPMancozebWater flea(Daphnia magna)Preliminary endpointsEC50= 471 μg form./L (mm)NOAEC = 312 μg form./L (mm)LOAEC = 601 μg form./L (mm)MRID 46096901In review46Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassification(67.8)Zoxamide(7.21)Freshwaterinvertebrate lifecycle: 21 days,flow-through(chronic)RH-117,281Technical(92.3)Water flea(Daphnia magna)21-day NOAEC = 39 μg a.i./L (mm)21-day LOAEC = 74 μg a.i./L (mm)(NOAEC based significant reduction in parental survival at≥74 μg/L)MRID 44731921AcceptableBenthicinvertebratechronic: 28 days,over-lying waterstatic exposure withsediment (chronic)RH-117,281Technical(92.3)14C-RH-117,281(97.81)Midge(Chironomusriparius)Overlying water exposureNOAEC < 210 μg a.i./L (mm)LOAEC = 210 μg a.i./L (mm)(based on reduced development;for emergence, NOAEC = 210 μga.i./L; LOAEC = 340 μg a.i./L)MRID 44731922Supplemental(due to nondefinitiveNOAEC)Estuarine/marineinvertebrate acute:96 hours, flowthroughRH-117,281Technical(92.3)Mysid shrimp(Mysidopsis bahia)LC50(95% C.I.) = 76 (67-87) μg a.i./L (mm)Probit slope (95% C.I.) = 9.0 (5.2-12.9)NOAEC = 17 μg a.i./L (mm)LOAEC = 31 μg a.i./L (mm)(NOAEC based on sublethal effect of erratic swimming at≥31 μg/L;lethargy at 132 μg/L – the highest treatment concentration)Very highly toxicMRID 44731923AcceptableRH-117,281Technical(92.3)Eastern oyster(Crassostreavirginica)EC50(95% C.I.) = 715 (535-957) μg a.i./L (mm)NOAEC = 123 μg a.i./L (mm)LOAEC = 238 μg a.i./L (mm)Highly ToxicMRID 44731924AcceptableEstuarine/marineinvertebrate lifecycle: 27 days,flow-through(chronic)RH-117,281Technical(92.3)14C-RH-7281(96.3)Mysid shrimp(Mysidopsis bahia)NOAEC = 7.2 μg a.i./L (mm)LOAEC = 14 μg a.i./L (mm)(NOAEC based on a reduction in reproduction and growth [length andweight])MRID 44731925AcceptableAquatic vascularplant: 14 days,static-renewalRH-117,281Technical(92.3)Duckweed(Lemna gibba)EC50(95% C.I.) = 19 (16-27) μg a.i./L (mm)NOAEC = 9.0 μg a.i./L (mm)LOAEC = 18 μg a.i./L (mm)MRID 44731945Acceptable47Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassification14C-RH-7281Technical(96.3)(NOAEC based on reduction in frond number; smaller-than-normalroot size at three highest concentrations)Aquatic nonvascular plant:96 hours, staticRH-117,281Technical(92.3)14C-RH-117,281(96.3)Green alga(Scenedesmussubspicatus)EC50(95% C.I.) = 10 (7.8-13) μg a.i./L (mm)NOAEC = 7.0 μg a.i./L (mm)LOAEC = 14 μg a.i./L (mm)(NOAEC based on reduction in cell density; clumping/flocculation andcellular enlargement at≥14 μg a.i./L)MRID 44731939Supplemental(due to testspecies)Form.:Dithane/RH117,281 DGBlendMancozeb(69)Zoxamide(8.26)Green alga(Selenastrumcapricornutum)EC50(95% C.I.) = 1.95 (1.52-2.51) μg zoxamide /L (TWA)NOAEC = 0.584 μg zoxamide /L (TWA)LOAEC = 1.16 μg zoxamide /L (TWA)EC50(95% C.I.) = 9.42 (7.38-12) μg mancozeb/L (TWA)NOAEC = 2.68 μg mancozeb /L (TWA)LOAEC = 5.17 μg mancozeb /L (TWA)EC50(95% C.I.) = 11.4 (8.91-14.2) μg form./L (TWA)NOAEC = 3.26 μg form./L (TWA)LOAEC = 6.33 μg form./L (TWA)(based on reduction in cell density)MRID 44950501AcceptableForm.:Dithane/ RH7281 (11.2:1)DG BlendMancozeb(70.9)Zoxamide(6.25)Green alga(Selenastrumcapricornutum)Preliminary endpointsEC50(95% C.I.) = 6.6 (5.5-7.9) μg zoxamide /L (im)+EC05(95% C.I.) = 1.7 (1.1-2.6) μg zoxamide /L (im)+NOAEC = <0.489 μg zoxamide /L (im)+EC50(95% C.I.) = 61 (52-73) μg mancozeb/L (im)+EC05(95% C.I.) = 16 (11-24) μg mancozeb /L (im)+NOAEC = <4.36 μg mancozeb/L (im)+EC50(95% C.I.) = 71 (61-80) μg form./L (im)+EC05(95% C.I.) = 23 (15-34) μg form./L (im)+NOAEC = <6.3 μg form./L (im)+(based on most sensitive endpoint of biomass)MRID 46056403In reviewRH-117,281TechnicalCyanobacterium(Anabaena flos-aqua)EC50> 860 μg a.i./L (im)NOAEC = 860 μg a.i./L (im)MRID 44731940Acceptable48Study TypeTest Substance(% a.i.)SpeciesToxicity Endpoints andAcute Toxicity Classification (If Applicable)Source& StudyClassification(92.3) (increase in cell density at≥100 μg a.i./L)Marine diatom(Skeletonemacostatum)EC50> 910 μg a.i./L (im)NOAEC = 490 μg a.i./L (im)LOAEC = 910 μg a.i./L (im)(NOAEC based on reduction in cell density; 14, 7.3, 3.7, 7.7, and 20%inhibition at 50, 110, 240, 490, and 910 μg/L in comparison to thenegative control)MRID 44731942AcceptableFreshwater diatom(Naviculapelliculosa)EC50> 930 μg a.i./L (im)NOAEC = 210 μg a.i./L (im)LOAEC = 410 μg a.i./L (im)(NOAEC based on reduction in cell density; 2.4, 46, 1.5, 36 and 43%inhibition at 60, 110, 210, 410, and 930 μg/L in comparison tonegative control)MRID 44770005AcceptableAquatic nonvascular plant: 120hours, staticRH-117,281Technical(92.9)Green alga(Selenastrumcapricornutum)EC50(95% C.I.) = 23 (18-30) μg a.i./L (mm)NOAEC = 4.1 μg a.i./L (mm)LOAEC = 8.6 μg a.i./L (mm)(NOAEC based on reduction in cell density)MRID 44731938AcceptableC.I. = confidence interval; form. = formulation; im = initial measured; mm = mean measured; nom = nominal; NS = not specified;TEP = typical end-useproduct; TWA = time-weighted average+The four lowest treatment levels of RH-7281 were not analytically verified. The concentration at each of these levels of RH-117,281 was calculated bymultiplying the percent of nominal recovery of RH-117,281 in the fifth lowest treatment level by the nominal concentration of RH-117,281.#endpoint calculated by multiplying the concentration in μg form./bee (as reported) by the % a.i.

# 49 Appendix D: Results of SIP and STIR

SIP (v1.0)

Table 1. Inputs

Parameter Value

Chemical name zoxamide

Solubility (in water at 25 o 

# C; mg/L) 0.681

Mammalian LD 50 

# (mg/kg-bw) 5000

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg-bw) 409.3

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian species

Avian LD 50 

# (mg/kg-bw) 2000

Avian test species mallard duck

Body weight (g) of "other" avian species

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 1000

Bobwhite quail NOAEC (mg/kg-diet) 1000

NOAEC (mg/kg-diet) for other bird species

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) 0.1171 0.1171

Adjusted toxicity value (mg/kg-bw) 3845.8028 314.8174

Ratio of exposure to toxicity 0.0000 0.0004

Conclusion* Drinking water exposure

alone is NOT a potential

concern for mammals Drinking water exposure

alone is NOT a potential

concern for mammals

Table 3. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 0.5516 0.5516

Adjusted toxicity value (mg/kg-bw) 1038.4508 49.6126

Ratio of exposure to acute toxicity 0.0005 0.0111

Conclusion* Drinking water exposure

alone is NOT a potential

concern for birds Drinking water exposure

alone is NOT a potential

concern for birds

*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.

# 50 STIR (v1.0)



# Welcome to the EFED Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining

the potential significance of the inhalation exposure route to birds and mammals in a

risk assessment.



# Input

Application and Chem ical Information

Enter Chemical Name zoxamide

Enter Chemical Use grapes

Is the Application a Spray? (enter y or n) y

If Spray What Type (enter ground or air) air

Enter Chemical Molecu lar Weight (g/mole) 336.1

Enter Chemical Vapor Pressure (mmHg) 1.00E-07

Enter Application Rate (lb a.i./acre) 0.21

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 

# (mg/kg bw) 2000

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD 50 

# (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC 50 

# (mg/L) 5.3

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35



# Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 

# ) 1.81E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.27E-04

Adjusted Inhalation LD 50 

# 1.18E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 

# 1.92E-05 Exposure not Likely

Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.02E-02

Ratio of Droplet Inhalation Do se to Adjusted Inhalation LD 50 

# 1.71E-03 Exposure not Likely

Significant



# Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 

# ) 1.81E-03

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.86E-04

Adjusted Inhalation LD 50 

# 3.16E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 

# 9.06E-07 Exposure not Likely

Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.54E-02

Ratio of Droplet Inhalation Do se to Adjusted Inhalation LD 50 

# 8.04E-05 Exposure not Likely

Significant