- Page 2 of 64

- terrestrial plants and terrestrial invertebrates is also uncertain. Uncertainty designations for taxa in this assessment are a result of incomplete ecotoxicology data, variability in environmental

exp osure estimations, or some combination of these factors. Where uncertainty designations are made for a taxon, efforts have been made to elucidate the risk picture. For instance, multiple lines of evidence support the potential for effects to non

- target t errestrial invertebrates, whereas for terrestrial plants, available lines of evidence indicate that the potential for risk is low.

Table 1 summarizes the representative uses assessed and the taxa that may potentially be directly at risk from exposure to h exythiazox

.Page 3 of 64 Table 1. Risk Resulting from Hexythiazox Exposure Presented by Taxon

Use Pattern Category 1 Aquatic

Invertebrates Fish (surrogate

for aquatic

- phase amphibians) Birds, (surrogate for

terrestrial

phase amphibians and reptiles) Mammals Plants Terrestrial

Invertebrates

Field Corn, Sweet Corn, Dry and Succulent Beans, Pepper, Eggplant, Alfalfa, Timothy, Ornamental lawns and turf, Non

residential turf, Sorghum,

Non

- bearing trees, Orchids, Christmas trees,

Ornamental non

- flowering plants, Ornamental shrubs and vines, Strawberry, Grapes, Dates Stone fruit, Pome fruit,

Tree nuts

, Hops, Caneberries, Christmas Trees, Potatoes, Mint,

Cott on Acute risk: Not expected; acute toxicity is limited by solubility

Chronic risk : Not expected for pelagic invertebrates;

uncertain for

sediment

dwelling

invertebrates Acute risk: Not expected; acute toxicity is limited by solubility

Chronic risk : Uncertain; risk

cannot be precluded for

freshwater or

estuarine/marine

fish Acute risk : Not expected

Chronic risk : Not expected Acute risk : Not expected

Chronic risk : Not expected Terrestrial:

Risk to listed

and non

listed plants

is uncertain

Aquatic: Not expected Non

- listed and

Listed: Uncertain;

likelihood of

risk

1 Risk conclusions apply to all registered hexythiazox use patternsPage 4 of 64 B a s i c Uncertainties

Due to hexythiazox’s activity as an acaricide , hazard to terrestrial arthropods is presumed to be greatest to egg, larval, and juvenile life stages. Although the available acute contact toxicity data for honey bees are nondefinitive, the response of the adult bees tested may not represent the

sensit ivity of other life stages (e.g., larvae, early instars). These different life stages represented in a healthy hive may be exposed to hexythiazox

- contaminated pollen from foragers. A honey bee larval toxicity study would be most useful to inform this unc ertainty; however, additional information regarding the timing of applications

— particularly whether or not applications occur during bloom

— would be useful in reducing uncertainty in assessing risk to non

- target terrestrial

invertebrates.

Since extract ion techniques were not sufficient in submitted environmental fate studies, unextracted residues (UER) are conservatively included in the calculation of estimated environmental concentrations (EECs). If UER are excluded from EECs, EECs are reduced by 30

t o 67%.

Quantitative Structure Activity Relationship (QSAR) mode ling is used to determine relative toxicities of hexythiazox degradates, which are considered in a toxic equivalency approach. In conjunction with the maximum occurrence of each degradate in environmental fate studies and degradate mobility data, it is projected that degradate exposure and toxicity could effectively increase EECs by 8 to 12%.

Finally, mites can occur through a broad portion of a crop year and applications can therefore occur over a broad range of time. This creates uncertainty as to when to assign the application date for aquatic exposure modeling. Additional information regarding hexythiazox usage, specifical ly concerning the timing of applications and geographical limitations of use, is of high

value to EFED.- Page 5 of 64

- 

## Environmental Fate and Ecological Risk Assessment for the Registration of Hexythiazox

Hexythiazox 

### (4 RS ,5 RS )

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 1,3

- thiazolidine

- 3

-

carboxamide
CAS Registry Number 

### 78587

- 05

- 0

PC Code 128849

Prepared by:
Andrew Shelby, Physical Scientist Nathan Miller, Biologist
U. S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch VI

1200 Pennsylvania Ave., NW

Mail Code 7507P Washington DC 20460 Reviewed by: Michael Wagman, Biologist, ERB VI
William P. Eckel, Ph.D, Senior Science Advisor, ERB VI
Mark Corbin, Branch Chief, ERB VI

J une 13 , 2013Page 6 of 64 

## Table of Contents

1. Executive Summary

................................ ................................ ................................ ................................ 7

2. Problem Formulation

................................ ................................ ................................ ........................... 11

2.1. Nature of Regulatory Action

................................ ................................ ................................ ..... 11

2.2. Mode of Action

................................ ................................ ................................ ........................... 12

2.3. Use Characterization

................................ ................................ ................................ .................. 12

2.4. Conceptual Model

................................ ................................ ................................ ...................... 14 3. Analysis

................................ ................................ ................................ ................................ .................. 19 3.1. Exposure Characterization

................................ ................................ ................................ .... 19 3.2. Ecological Effects Characterization

................................ ................................ ...................... 34

4. Risk Characterization

................................ ................................ ................................ ........................... 40

4.1. Risk Estimation

................................ ................................ ................................ ....................... 40 4.2. Risk Description

................................ ................................ ................................ ...................... 47

5. Federally Threatened and Endangered (Listed) Species Concerns

................................ .................. 50

5.1. Action Area

................................ ................................ ................................ .............................. 51

5.2. Taxonomic Groups Potentially at Risk

................................ ................................ .................. 51

6. Literature Cited

................................ ................................ ................................ ................................ .... 54Page 7 of 64 1. Executive Summary

EFED has completed the R egistration R eview preliminary ecological risk assessment for hexythiazox (5

- (4

- chlorophenlyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 3

- thiazolidenecarboxamide (DPX

- Y5893) ; CAS#: 78587

- 05

- 0 ; PC Code: 1 28849 ) and its end

- use product s

. Hexythiazox is

a n acaricide that acts primarily as a mite growth inhibitor/ ovicide and is used to control mites. It

is formulated into wettable powder, water dispersible granules, and emulsifiable concentrate

. Hexythiazox is currently registered for use on a variety of agricultural crops, turf, and various residential plants

. It can be applied as a liquid foliar spray by air or ground application equipment

. The c urrently registered maximum single application rate of hexythiazox is 0.1875

lb a.i./A. Recent hexythiazox ecological risk assessments include the Section 3 incremental new

use assessment for sorghum (USEPA, 2013 b ; D 404023 ), the Section 3 new use assessment for alfalfa, timothy, eggplant, and peppers (USEPA, 2012 a ; D396529+), the Section 3 new use

assessment for field corn, sweet corn, dry beans, succulent beans and greenhouse t omatoes (USEPA, 2011 ; D364594+), the Section 3 new use assessment for turf and various residential plants (USEPA, 2010; D334885 )

, a Section 3 new use assessment on potatoes in the Pacific

N orthwest (USEPA, 2009; D338695), and a n initial P roblem F ormulation for the for Registration R eview (Document Number: EPA

- HQ

- OPP

- 2006

- 0114). The two most recent n ew

use assessments (D404023 and D396529+) have been conducted with the total toxic residues ( TTR ) approach ; preceding assessments additionally consid ered unextracted residues (UER) in exposure estimates

.

Parent hexythiazox is moderately persistent. It degrades to transformation products with a half life of 27 to 43 days in aerobic soil and 30 to 40 days in aerobic aquatic systems. It is stable to hydrolysis though photolyzes in water with a half life of 17 days. Parent hexythiazox is slightly

mobile with a K OC of 6,188 mL/g o.c.

Unextracted residues (UER) are assumed to be hexythiazox and bioavailable due to insufficient extractions and high un extracted residues in metabolism studies in comparison to improved extractions and lower unextracted residues in a field lysimeter study. UER and hexythiazox degrade in aerobic soil with half lives ranging 90 to 102 days and in aerobic aquatic systems wit h half lives ranging 76 to 110 days. Hexythiazox is stable to hydrolysis though photolyzes in water with a half life of 17 days.

Given the low solubility (0.12 ppm) of the compound and its propensity to sorb, it is likely that the compound will readily partition to soil and sediments. Hexythiazox is not expected to

bioaccumulate in aquatic organisms. A peak BCF (whole fish) for bluegill sunfish was found to be 1,000 to 1,600. Hexythiazox is not likely to volatilize given its vapor pressure (1 x 10 - 8 mm Hg at 20 o C and Henry’s Law constant=. 3.87 x 10 - 8 m 3 atm g/mol at 20 o C) ). Although the compound is considered slightly mobile, it may access water through runoff of sediment

- bound residues (erosion).

H exythiazox is not acutely toxic to freshwater and estuarine/marine fish and invertebrates at its

limit of solubility. On a chronic exposure basis, hexythiazox resulted in decreased survival, reproduction (number of young/female), and growth (weight and length) of freshwaterPage 8 of 64 invertebrate s and decreased reproduction (number of young/female and interbrood duration) and growth (length) of estuarine/marine invertebrates. Chronic toxicity data are not available for

fish. H exythiazox is practically nontoxic to birds, mammals, and beneficial i nsects ( i.e. , honey bees) on an acute exposure basis as no effects were recorded in the available studies ( i.e. , the no effect level was greater than the highest concentration tested)

. Chronic toxicity testing with mammals did not identify an adverse resp onse threshold and while significant treatment

- related reductions in food consumption were determined from a chronic avian study , the study NOAEC is more than two times greater than the maximum EECs and the likelihood of adverse effects

from chronic exposu re is considered low for avian species

. Based on the available plant toxicity data, hexythiazox exhibited low toxic ity to aquatic plants , but may exhibit toxicity to some species of terrestrial plants.

Degradates of hexythiazox are considered in a toxic equivalency approach. Using QSAR to estimate toxicity, the maximum occurrence of each degradate in environmental fate studies and degradate mobility data, it is estimated that degradate exposure and toxicity could effectively increase EECs by 8 to 12%.

P otential effects to federally

- listed endangered and threatened species (listed species) based on LOC exceedances require an in

- depth listed species evaluation determining the potential co

occurrence of listed species and use patterns of hexythiazox . Ident ified potential risks to listed species are summarized in Table 1

.

Table 1. Potential Effects to Federally Listed Taxa Associated with Direct Effects from the Registered Uses of H exythiazox

. Listed Plant Taxon Potential Direct Effects

Terrestrial and semi

- aquatic plants

– monocots and dicots Uncertain 1

Aquatic nonvascular plants No Aquatic vascular plants No

Listed Animal Taxon Potential Direct Effects

Acute Chronic

Terrestrial invertebrates Uncertain 2 Uncertain 2

Mammals No 3 No 3

Birds No 3 No 3

Reptiles No 3 No 3

A mphibians No 5 Uncertain 4

Freshwater fish No 5 Uncertain 4

Freshwater invertebrates No 5 Uncertain 6

Mollus k s Uncertain 7 ND

E stuarine /marine fish No 5 Uncertain 4

E stuarine /marine invertebrates No 5 Uncertain 6

ND = Not determined

1 Tier I terrestrial plant testing is incomplete; tier II seedling emergence data is not available for two species that demonst rated effects greater than 25% in tier I testing. Only one tier I vegetative vigor study used TEP for testing (all ot her available tier I vegetative vigor and seedling emergence studies used TGAI); this study only tested response of six species.

2 Although no effects were seen in the acute contact toxicity tests with honey bees, the limit dose (200 μg a.i./bee) was not h igh enough to preclude risk at the listed species LOC (0.4) , based on the tall grass EECs (

~ 20,000 ppb) for registered hexythiazox uses. Further, given that hexythiazox affects eggs and larval life stages of the intended pest arthropods , EFED cannot precl ude effects to this taxon.

3 Risk of direct effects from acute and chronic exposure of avian (including reptilian surrogates) and mammalian species to for mulated hexythiazox is expected to be below the LOC.

4 No chronic fish toxicity studies have been su bmitted. Fish are surrogates for aquatic phase amphibians.Page 9 of 64 5 Solubility issues confound the results of acute toxicity testing; no definitive LC/EC 50 values were determined. The acute toxicity of hexythiazox appears to be limited by its solubility.

6 No chronic sediment toxicity studies have been submitted. Hexythiazox’s MOA in conjunction with effects to reproduction obse rved from chronic pelagic invertebrate testing raise chronic risk concerns for sediment dwelling aquatic invertebrates.

7 No acute bivalve studies have been submitted

Based on this screening

- level assessment, acute risk resulting from direct effects is not expected for listed birds, mammals, freshwater and estuarine/marine fish (surrogates for aquatic

- phase amphibians), and freshwater and estuarine/marine invertebrates from the use of hexythiazox on all of its registered use sites. Chronic risk resulting from direct effects to listed freshwater and estuarine/marine fish (surrogates for aquatic

- phase amphibians), freshwater a nd estuarine/marine invertebrates, and terrestrial invertebrates and terrestrial plants is uncertain from the use of hexythiazox on all of its registered use sites

. Potential direct effects on listed terrestrial invertebrates and terrestrial plants and no n

- listed terrestrial invertebrates and terrestrial plants

from the use of hexythiazox may be associated with modification of primary constituent

elements (PCEs) of designated critical habitat , where such designations have been made. However, at this curre nt stage of the Registration Review process, it is premature to make effects determinations until further refinements are conducted. In order to make species

- specific effects determinations, useful refinem ents include more detailed 1) species

- specific eco logical and biological data; 2) information on use patterns for hexythiazox ; and 3) sub

- county level spatial proximity analyses for the co

- occurrence of potential areas of effects and listed species/designated critical habitat s of concern. Examples of suc h refinements are described

below.

EFED is currently developing tools that are expected to further refine the species

- specific assessment and designed to aid in making effects determinations for individual listed species and/or their designated critical habitats (if applicable). I nformation obtained from the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS), and other reliable sources is being collated by EFED to address all currently listed species. The information will be stored in an Office of Pesticide Programs P esticide Registration Information Syste m (PRISM) knowledgebase, which consists of an information repository for biological and behavioral data relevant to specific species and/or their habitats) and a document repository that contains supporting documents (e.g., USFWS recovery plans) and electronic information ( e.g ., GIS data files). These data will be relied upon to provide information on habi tat, diet, life history variables, and temporal and spat ial data. For terrestrial taxa specifically, the biological information relevant to Risk Quotient (RQ) calculations ( e.g ., diet and body weight) will be used to parameterize exposure estimates to der ive species

- specific RQs consistent with currently used

methods in the T

- REX and T

- HERPS models.

Refinements may also include more detailed analyses of the registered uses and their use patterns

that result in level of concern ( LOC ) exceedances for list ed species in the screening

- level assessment. The analyses may include more information on where, when, and how heyxthiazox is used on crops including: alfalfa, timothy, caneberries, Christmas trees, citrus, cotton, dates, dry beans, succulent beans, fiel d corn, sweet corn, grapes, hops, mint, non

- bearing trees, orchids,

ornamental non

- flowering plants, ornamental shrubs and vines, peppers, eggplants, pome fruit, potatoes, sorghum, stone fruit, strawberries, tree nuts, and turf . Actual usage data (when

av ailable) and national land

- cover datasets that indicate potential use sites ( e.g ., national landPage 10 of 64 cover dataset (NLCD), crop data layer (CDL)) may be used to support a more refined analysis of

where hexythiazox is reasonably expected to be used. Similarly, refinements for the timing of applications and how hexythiazox is used may involve an analysis of reported usage data (if available) and a more in

- depth exploration of agronomic practices.

The U.S. Environmental Protection Agency (EPA) , along with the U.S. Department of Agriculture (USDA), the U.S. Fish and Wildlife Service (FWS), and the National Marine Fisheries Service (NMFS), have announced the availability of a report developed by the National Academy of Sciences’ National Research Council outlinin g recommendations on specific scientific and technical issues related to the development of endangered and threatened species risk assessments for pesticides that are compliant with the Endangered Species Act (ESA) and the Federal Insecticide, Fungicide, a nd Rodenticide Act (FIFRA). The EPA, USDA, FWS and NMFS asked the NRC to consider a range of scientific and technical issues including:

• identifying best available scientific data and information;

• considering sub

- lethal, indirect and cumulative effects ;

• assessing the effects of chemical mixtures and inert ingredients;

• analyzing the effects of pesticide use through the use of models;

• incorporating uncertainties into the evaluations; and

• using geospatial information and datasets that can be em ployed by the agencies in the

course of these assessments.

After reviewing the NRC’s recommendations on these scientific and technical issues, the EPA and its federal partners will determine how these recommendations can be implemented and incorporated i nto the scientific approaches for developing listed species risk assessments. It is anticipated that any draft guidance and/or science policies developed by EPA and its federal partners as a result of the NAS recommendations would be released for public co mment prior to implementation.

The refinements based on species

- specific data and detailed usage information, when available, are expected to help to more accurately identify potential areas of effect and to better inform

effects and habitat determinatio ns for listed species and any designated critical habitats. For example, if hexythiazox is used when a particular species of concern is not present (e.g., it is migratory) or is not co

- located in space, then risk to the species may often be precluded. If LOCs are still exceeded for birds (surrogates for terrestrial

- phase amphibians and reptiles), mammals, terrestrial invertebrates and terrestrial plants after conducting the refined analyses, further analyses of the potential spatial/temporal co

- occurrence of listed species of concern (and any designated critical habitat) may be conducted. The extent of possible refinement in the analyses of spatial/temporal co

- occurrence will largely depend on the scale and quality of the

available sub

- county level use s ite (e.g., NLCD, CDL) and species location data

.

Uncertainties

The conclusions of this risk assessment are limited by uncertainties concerning both exposure and toxicity

. Since extraction techniques were not sufficient in submitted environmental fate studies, unextracted residues (UER) are conservatively included in the calculation of estimatedPage 11 of 64 envir onmental concentrations (EECs). The maximum occurrence , mobility, and toxicity of hexythiazox transformation products are further uncertainties which are addressed through a toxic equivalency approach ; toxicity estimates derived from a Quantit ative Structural Activity Relationship (QSAR) model for each degradate are compared to toxic ity relative to parent hexythiazox and weighted relative to their maximum occurrence in environmental fate studies. Each toxic equivalency for each degradate is added together to represent the additional risk from hexythiazox degradates. Available e colog ical effects data are not sufficient to assess the hazard of hexythiazox to fish and sediment

- dwelling aquatic invertebrates on a chronic basis, larval honey bees, and terrestrial plant s . Lines of evidence are explored in this assessment to determine

the magnitude of the uncertainty on the likelihood for direct effects for each taxon.

2. Problem Formulation

The purpose of problem formulation is to provide the foundation for the environmental fate and ecological risk assessment in support of the Registra tion Review of the acaricide hexythiazox (5

- (4

- chlorophenlyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 3

- thiazolidenecarboxamide (DPX

- Y5893) ; CAS#: 78587

- 05

- 0 ; PC Code: 128849 ) ) . The problem formulation sets the objectives for the risk assessment, establishes a risk hypothesis and conceptual model depicting potential risk, and provides a plan for analyzing the data and characterizing the risk associated with the use s of hexythiazox (USEPA, 1998).

2.1. Nature of Regulatory Action

Under the Federal Insecticide, Fung icide, and Rodenticide Act (FIFRA), all pesticides distributed or sold in the United States must be registered by the United States Environmental Protection Agency ( EPA or the Agency ). To determine whether a pe sticide can be registered, the EPA

evaluates the product’s safety to non

- target species based on a wide range of environmental and health effects studies. In 1996, FIFRA was amended by the Food Quality Protection Act (FQPA), and EPA was mandated to implement a new program for the periodic review of pesticides, i.e

., R egistration R eview 1 . The registration review program is intended to ensure that as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreason able adverse effects to human health and the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to

make sure that as cha nge s occur , products in the marketplace can be used safely.

Additionally , potential effects to Federally listed endangered and threatened species (hereafter

referred to as “listed” ) and their designated critical habitat are also considered under the

Endan gered Species Act (ESA) in order to ensure that the continued registration of hexythiazox is not likely to jeopardize the continued existence of listed species or adversely modify their critical habitat. In order to meet the requirements of FIFRA and the ESA, this assessment follows EPA guidance on conducting ecological risk assessments (USEPA, 1998) and Office of

1 http://www.epa.gov/oppsrrd1/registration_review/Page 12 of 64 Pesticide Program’s Overview Document, which contains guidance for assessing pesticide risks

to non

- listed and listed species (USEPA, 2004).

Recent hexythiazox ecological risk assessments include the Section 3 incremental new use

assessment for sorghum (USEPA, 2013 b ; D 404023), the Section 3 incremental new use

assessment for alfalfa, timothy, eggplant, and peppers (USEPA, 2012 a ; D396529+), the Section

3 incremental new use assessment for field corn, sweet corn, dry beans, succulent beans and greenhouse t omatoes (USEPA, 2011; D364594+), the Section 3 incremental new use assessment for turf and various residential plants (USEPA, 2010; D334885 ), a Section 3 new use assessment on potatoes in the Pacific Northwest (USEPA, 2009; D338695), and a Problem Formulation for the Summary Document for Registration Review (Document Number: EPA

- HQ

- OPP

- 2006

- 0114).

2.2

. Mode of Action

Hexythiazox is an acaricide used to control several mite species on a variety of agricultural

cr ops, turf, and residential plants

. Hexythiazox belongs to the thiazolidine class of pesticides. Its mode of action is unknown. It is a mite growth inhibitor that acts primarily as an o vicide, with some effect on early instars.

2.3

. Use Characterization

Hexythiazox is formulated as a wettable powder, water dispersible granule, and emulsifiable

concentrate

. Hexythiazox can be applied either by aerial equipment or ground equipment to row

crops , orchard crops, vineyards , turf and ornamentals. It can also be applied by irrigation equipment ( i.e. , chemigation)

. Labeled use patterns for h exythiazox are summarized in Table 2

, below

.

Table 2. Hexythiazox Uses by Label

Label Formulation %

a.i. Uses # of

apps Method of App

10163

- 208 Wettable

Powder 50 Caneberries, Christmas Trees, Citrus (CA, AZ, and TX), Cotton (CA), Dates, Grapes, Hops, Pome Fruits, Stone Fruits, Strawberries, Tree Nuts,

and Pistachios 1 Ground and

Air

10163

- 250 Water Dispersible

Granule 50 Caneberries, Christmas Trees, Citrus (CA, AZ, and TX), Cotton (CA), Dates, Grapes, Hops, Pome Fruits, Stone Fruits, Strawberries, Tree Nuts,

and Pistachios 1 Ground and

Air

10163

- 251 Water Dispersible

Granule 50 Ornamental Pl a nts and Nonbearing Fruit Trees; Vines Growing in Nurseries; Greenhouses,

Shadehouses and Christmas Tree 1 Ground and

AirPage 13 of 64 Plantations; Established Ornamental Landscape Plantings; Ornamental Lawns and Turf; Non

- residential Turf; Pome Fruit; Stone Fr uit; Nut Trees; Caneberrie s; Orchids

10163

- 277 Emulsifiable

Concentrate 11.8 Alfalfa, Timothy ; Beans * (dry and succulent); Citrus (CA, AZ, and TX); Cotton (CA); Corn (field and

sweet * ); Christmas trees; Small fruit vine climbing subgroup (except fuzzy kiwifruit); Greenhouse
tomatoes; Non

- bearing tree fruits and nuts, citrus, and vines (field grown and nursery) ; Pepper/Eggplant Subgroup 8

- 10B; Pome fruit group

11

- 10; Potatoes (OR, WA, and ID); Stone fruits group; Tree nuts group and pistachios 1 Ground and

Air

1016 3

- 303 Emulsifiable

Concentrate 48 Caneberr ies; Christmas Trees; Citrus (CA, AZ, and TX); Cotton (CA); Dates; Grapes; Hops; Pome Fruits; Stone Fruits, Strawberries; Tree Nuts; Pistachios; Corn *; Potatoes (OR, WA, and ID); Ornamental

Pl ants and Nonbearing Fr uit Trees; Vines Growing in Nurserie s, Greenhouses, Shadehouses, Established Ornamental Landscape Plantings, Orchids 1 Ground and

Air

10163

- 321 Emulsifiable

Concentrate 24.2 Citrus (CA, AZ, TX), Cotton (CA), Grapes, Pome Fruits, Stone Fruits,

Tree Nuts 1 ** Ground and

Air

83529

- 28 Emulsifiable

Concentrate 24.2 Christmas Tree, Non

- bearing tree fruits and nuts, citrus, and vines,

Non

- bearing crops or perennial

crops , Field corn, Citrus (CA, AZ, TX), Cotton (CA), Grapes, Pome Fruits, Stone Fruits, Tree Nuts,

Potatoes (WA, OR, and ID) 1 Ground and

Air

* Dry beans, succulent beans, and sweet corn are all use

- restricted to the western United States

** Label statement: “ Do not make more than one application of GWN

- 426 per year ” does not restrict from applying other hexythiazox products

A screening level estimate of current usage of hexythiazox is presented in Table 3

. This screening level us age assessment presents usage data on an annual basis and is derived fromPage 14 of 64 USDA’s National Agricultural Statistics Service with data updated to 2008. This analysis amounts to 18,500 pounds of active ingredient used nationally on an annual basis with use on almonds, strawberries, and w alnuts being the dominant use patterns

. Thou gh these data are indicative of a small use pattern, new uses on 10 crops and various non

- agriculture uses have been approved si nce this analysis was performed and may contribute to a larger and broader use

pattern.

Table 3. Hexythiazox Screening Level Usage Analysis (SLUA) for 2008

Crop Lbs. A.I. Percent Crop Ttd.
Avg. Max.

1 Alfalfa <500 <1 <2.5

2 Almonds 4,000 5 10

3 Apples 1,000 <2.5 5

4 Apricots <500 5 10

5 Caneberries 1,000 15 20

6 Cherries <500 <2.5 5

7 Dates (Section 18 Use) <500 10 10

8 Grapes 1,000 <1 <2.5

9 Nectarines 1,000 10 20

10 Oranges (Section 18 Use) <500 <1 <2.5

11 Peaches 1,000 5 15

12 Pears <500 5 10

13 Plums <500 5 10

14 Prunes 1,000 5 10

15 Strawberries 3,000 25 35

16 Walnuts 2,000 5 15

2. 4

. Conceptual Model

The potential terrestrial and aquatic exposure pathways and effects of the registered uses of hexythiazox are shown in Figure 1 . The conceptual model used to depict the potential ecological risk associated with the registered use s of hexythiazox as sumes that, as an acaricide, hexythiazox is capable of adversely affecting terrestrial and aquatic animals and plants, provided

that environmental concentrations are sufficiently elevated as a result of the label ed uses. Solid

arrows in Figure 1 depict the most likely routes of exposure and effects; dashed lines depict potential routes of exposure that are not considered likely for hexythiazox.Page 15 of 64 Foliage applied Hexythiazox and its resulting degradates STRESSOR

Volatilization/ Wind Suspension Spray Drift Runoff/ Erosion Leaching (Infiltration)/

Percolation Direct Deposition SOURCE/
TRANSPORT
PATHWAYS

Terrestrial Food Residues (foliage, fruit, seeds, insects) Upland Foliage/ Soil Riparian/

Wetland Foliage/ Soil Receiving Water Body/

Sediment Groundwater

Terrestrial

Upland
Plants Riparian/

Wetland

Plants Terrestrial Vertebrates (Birds, Mammals, Reptiles, Terrestrial Phase Amphibians) Aquatic
Plants Aquatic

Invert. &

Vertebrates

Plant Population:

Reduced Population

Growth,

Biomass Individual Animals: Reduced Survival, Growth,

Reproduction, Individual Invertebrates,

Vertebrates:

Reduced Survival, Growth, Reproduction Individual Plants: Reduced Seedling Emergence, Vegetative Vigor Ingestion Direct Contact Root Uptake Uptake/ Adsorption Gill/ Integument

Uptake Direct Contact Root Uptake SOURCE/ EXPOSURE

MEDIA

EXPOSURE ROUTE

RECEPTORS

ATTRIBUTE

CHANGE Ingestion Up

the Food

Chain

Piscivorous
Vertebrates

Individual Animals : Reduced Survival, Growth, Reproduction Epibenthic,

and Benthic

Invertebrates

Epibenthic and

Benthic Animals: Reduced Survival, Growth, Reproduction Ingestion/
Gill/ Integument

Uptake

Figure 1

. Conceptual Model of the Transport and Effects of Hexythiazox in Terrestrial and Aquatic Environment s *Dotted lines indicate that, although this exposure route/media was considered, its contribution to the fate and transport of hexythiazox is expected to be negligiblePage 16 of 64 The hypothesis for the risks of hexythiazox to non

- target animals focuses on both aquatic and terrestrial environments via potential exposure to the parent from direct spray, spray drift, and

runoff. Leaching is not considered a significant route of transport considering hexythiazox is slightly to hardly mobile in water. For terrestrial organisms, the major route of exposure is via

diet , such as through consumption of plant leaves or insects, which contain hexythiazox residues

as a result o f direct application and/or spray drift. For aquatic animal species, the major routes of exposure are direct contact via the respiratory surface (gills) or the integument. Aquatic vascular

and non

- vascular plants may also be exposed via direct uptake and adsorption. Risk to terrestrial plants is also considered in this screening

- level assessment. In addition, hexythiazox has a strong potential for adsorption to sediment; therefore, exposure to benthic organisms from sediment (pore water) and ingestion o f residues by invertebrates and fish is possible. Estimated exposure concentrations for all organisms are obtained through the use of several Agency exposure models.

The following risk hypothesis is presumed for this screening level assessment:

Based on the application methods, mode of action, direct toxicity to non

- target aquatic and terrestrial species, the registered uses of hexythiazox have the potential to reduce survival, reproduction, and/or growth in listed and non

- listed terrestrial and aquatic o rganisms.

Analysis Plan

Residues of Concern

The stressors of ecological concern for aquatic and terrestrial organisms are hexythiazox

, degradates of similar chemical structure, and unextracted residues (UER)

. Hexythiazox and UER are summed together in a total toxic residues (TTR) approach

. In this approach, a single exposure concentration is estimated for total residues and compared to a representative toxicity endpoint for the parent. To estimate exposure

, the amounts of UER in fate studies are added and

the sum of residues will be used to estimate a half

- life that is in turn used in model inputs. Degradates PT

- 1

- 2, PT

- 1

- 3, PT

- 1

- 4, PT

- 1

- 5, PT

- 1

- 8, and PT

- 1

- 9 are considered separately in a

toxic equivalency approach. In this approach, toxicity endpoi nt estimates from a QSAR model for each degradate are compared to toxicity relative to parent hexythiazox and weighted relative

to their maximum occurrence in environmental fate studies. Each toxic equivalency for each degradate is added together to repre sent the additional risk from hexythiazox degradates. The issue of inclusion of degradates of concern and UER are uncertainties in this assessment.

Mixtures

Evaluation of pesticide environmental mixtures is beyond the scope of this assessment because

of myriad factors that cannot be quantified based on the available data. Those factors include identification of other possible co

- contaminants and their concentrations, differences in the pattern and duration of exposure among contaminants, and the differe ntial effects of other physical/chemical characteristics of the receiving waters ( e.g. organic matter present in sediment and suspended water). Evaluation of factors that could influence additivity/synergism is beyondPage 17 of 64 the scope of this assessment and the capabilities of the available data to allow for an evaluation. However, it is acknowledged that not considering mixtures could over

- or under

- estimate risks depending on the type of interaction and factors discussed above

.



### Measures of Exposure

EFED use s standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

.

Since the previous e xposure assessments were completed, three main changes in standard procedures were made:

1) Transformation rates for fate studies were recalculated according to the North American Free Trade Agreement (NAFTA) Guidance for Evaluating and Calculating Degrada tion Kinetics

in Environmental Media ( Bohaty et al. , 2012 ; NAFTA, 2012 )

. These updated results will be used in estimating model inputs for estimating aquatic exposur e. 2) A new model for estimating concentrations in groundwater was developed called the

Pesticide Root Zone Model

– Groundwater (PRZM

- GW) ( Baris et al. , 2013 ) . This model will be used along with SCI

- GROW to estimate concentrations in ground water. 3) Residues of concern for ecological risk were updated. Estimated environmental

concentrations (EEC s ) will reflect exposure to all two or three ring structures with some resemblance to hexythiazox.

The most up to date procedures and models are used in the Registration Review exposure

assessments.



### Measures of Effect

Selected toxicity data are used to calculate risk estimates . Any additional information submitted by the registrant or found in the open literature are also to be considered. The open literature studies are identified using EPA’s ECOTOX icity (ECOTOX) 2 da tabase , 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.



### Endangered Species Assessments

Consistent with the Agency’s responsibility under the End angered Species Act (ESA), the Agency evaluate s potential risks to listed species from registered uses of pesticides in Registration Review . These assessments are conducted in accordance with standard EPA

2 http://cfpub.epa.gov/ecotox/Page 18 of 64 procedures and good scientific judgment. The proce ss for evaluating potential risks to listed species is further described in the Overview Document at http://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

.



### Endocrine Disrup tor Screening Program

As required by FIFRA and the Federal Food Drug and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmen tal and reproductive effects in different taxonomic groups. As part of its reregistration decision, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as re quired by FFDCA section 408(p), hexythiazox is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredien ts) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required

d eterminations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are foun d to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify an y adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October

2009 and Febru ary 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Hexythiazox is not among the group of 58 pesticide active ingredients on the initial list to be sc reened under the EDSP. Accordingly, as part of Registration Review, EPA will issue future EDSP orders/data

call

- ins, requiring the submission of EDSP screening assays for hexythiazox . For further information on the status of the EDSP, the policies and proc edures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.Page 19 of 64 3. Analysis

3.1. Exposure Characterization

3.1.1. Environmental Fate and Transport Characterization

Parent hexythiazox is moderately persistent. It degrades to the identified transformation products with a half life of 27 to 43 days in aerobic soil and 30 to 40 days in aerobic aquatic systems. It is st able to hydrolysis though photolyzes in water with a half life of 17 days.

Unextracted residues (UER) are assumed to be hexythiazox and bioavailable due to insufficient

extractions and high unextracted residues in metabolism studies in comparison to impro ved

extractions and lower unextracted residues in a field lysi meter study . The aerobic soil metabolism study reports UER of 34.1% to 50.0% of applied hexythiazox after 153 days though only 20% methanol/water extraction was used. In contrast, UER in the f ield lysimeter study accounted for 11% to 35% of applied hexythiazox after one year with a methylene chloride

extraction and occasional Soxhlet extractions.

UER and hexythiazox degrade in aerobic soil with half lives ranging 90 to 102 days and in

aerobi c aquatic systems with half lives ranging 76 to 110 days. Hexythiazox is stable to hydrolysis though it photolyze s in water with a half life of 17 days. Parent hexythiazox is slightly mobile with a K OC of 6,188 mL/g o.c.

Parent hexythiazox is initiall y transformed to PT

- 1

- 4, PT

- 1

- 5, PT

- 1

- 8, or PT

- 1

- 9, all representing an oxidation of the cyclohexane ring ( Table 4 ) . Subsequent transformation products involve the cleavage of the cyclohexane group (PT

- 1

- 3) and further degradation involves the cleavage of the amide group (PT

- 1

- 2). PT

- 1

- 2, PT

- 1

- 3, PT

- 1

- 4, PT

- 1

- 5, PT

- 1

- 8, and PT

- 1

- 9 are all included as

toxic residues in the toxic equivalency approach

.

Degradates of hexythiazox are persistent to metabolic and abiotic degradation and moderately to slightly mobile in soil. Degradates of hexythiazox are moderately mobile and are significantly more mobile than parent hexythiazox with the lowest average K OC for PT

- 1

- 2 being 406 mL/g

o.c. Degradates are not likely to volatilize as parent has a vapor pressure of 1x 10 - 8 mm Hg and modeled degradate vapor pressures are less than the modeled parent vapor pressure ( EPISuite ).

Residues can dissipate in the environment through a variety of degradation an d transport processes. Residues are prone to leaching and run off as less mobile parent material is more prone to run off and less mobile degradates are more prone to leaching

. Residues are persistent but can be degraded thr ough metabolism or photolysis. Field lysimeter studies found residues in the top layer of soil persisting at 64% to 94% of applied radioactivity at one year post application. Residues in the soil column were present at concentrations as high as 9.5% (8

- 16 cm), 2.2% (16

- 24cm), and 1.9 % (24

- 32cm). Concentrations of PT

- 1

- 4, PT

- 1

- 8, and PT

- 1

- 9 peaked at 4 to 16 weeks with a peak of 12.4% applied radioactivity (PT

- 1

- 9; 16 weeks; California). Concentrations of PT

- 1

- 2 and PT

- 1

- 3 peaked at 16 to 52 weeks with a peak of 19.4% applied radioac tivity (PT

- 1

- 2; 16 weeks; Mississippi).Page 20 of 64 Table 4 . Hexythiazox and Its Environmental Degradates.

Code Name/ Synonym Chemical Name and Available

Fate Data Chemical Structure Study Type Ref.

(MRID) Maximum %AR (day) Final %AR (study length)

PARENT

Hexythiazox

NA

- 73 IUPAC: (4 RS ,5 RS )

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 1,3

- thiazolidine

- 3

- carboxamide

CAS: (4 R ,5 R )

- rel

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 3

- thiazolidinecarboxamide

CAS No.: 78587

- 05

- 0

Formula: C 17 H 21 ClN 2 O 2 S

MW: 352.88 g/mol

SMILES: C1=C(C=CC(=C1)C2C(C)N(C (S2)=O)C(NC3CCCCC3)=O)Cl

TRANSFORMATION PRODUCTS

PT

- 1

- 2 5

- (4

- chlorophenyl)

- 4

- methyl

- 2

-

oxo

- thiazolidine

- 3

- carboxamide

SMILES: C1=C(C=CC(=C1)C2 C(C)N(C(S2)=O)C(N)=O)Cl

K OC : 406 mL/g o.c. (MRID 48743402) Hydrolysis

22 ° C 00141516 ND NDPage 2 1 of 64 Code Name/ Synonym Chemical Name and Available

Fate Data Chemical Structure Study Type Ref.

(MRID) Maximum %AR (day) Final %AR (study length)

Aq. photolysis 00146538 3.1% (210 m) 2.8% (300 m)

Aerobic soil 00141515 22.2% (28 d) 18.6% (84 d)

Field studies 00156892 10.5% (26 w) 9.2% (52 w)

Aerobic Aquatic

Metabolism 48910702 32.8% (100 d) 32.8% (100 d)

Aerobic Soil

Metabolism 48743403 39.5% (122 d) 36.5% (153 d)

Anaerobic Aquatic

Metabolism 48743405 21.0% (360 d) 21.0% (360 d)

PT

- 1

- 3 5

- (4

- chlorophenyl)

- 4

- methyl

thiazolidin

- 2

- one

Formula: C 10 H 10 ClNOS

MW: 227.71 g/mol

SMILES: C1=C(C=CC(=C1

)C2C(C)NC(S2)=O)Cl

K OC : 446 mL/g o.c. (MRID 48743402) Hydrolysis

22 ° C pH 5 pH 7 pH 9 00141516 0.8% (0 h) 0.3% (336 h) 7.0% (1368 h) 0.3% (840 h) 0.15% (888 h) 7.0% (1368 h)

Aq. photolysis 00146538 1.2% (210 m) 1.0% (300 m)

Aerobic soil 00141515 5.8% (28 d) 5.4% (84 d)

Field studies 00156892 5.6% (52 w) 5.6% (52 w)

Aerobic Aquatic

Metabolism 48910702 4.9% (100 d) 4.9% (100 d)

Aerobic Soil

Metabolism 48743403 9.2% (90 d) 9.1% (153 d)

Anaerobic Aquatic

Metabolism 48743405 3.2% (360 d) 3.2% (360 d)Page 22 of 64 Code Name/ Synonym Chemical Name and Available

Fate Data Chemical Structure Study Type Ref.

(MRID) Maximum %AR (day) Final %AR (study length)

PT

- CY

- OH

(mixture of PT

- 1

- 4

and PT

- 1

- 8) See PT

- 1

- 4 and PT

- 1

- 8 See PT

- 1

- 4 and PT

- 1

- 8 Hydrolysis

22 ° C 00141516 ND ND

Aq. photolysis 00146538 3.1% (210 m) 2.9% (300 m)

Aerobic soil 00141515 4.1% (7 d) 7.1% (84 d)

Anaerobic Aquatic

Metabolism 48743405 14.9% (360 days) 14.9% (360 days)

PT

- 1

- 4

5

- (4

- chlorophenyl)

- N

- (3

- hydroxycyclohexyl)

- 4

- methyl

- 2

-

oxo

- thiazolodine

- 3

- carboxamide

SMILES: C1=C(C=CC(=C1)C2C(C)N(C(S2 )=O)C(NC3CC(CCC3)O)=O)Cl Field studies (PT

- 1

- 4) 00156892 3.6% (16 w) 1.6% (52 w)

Aerobic Aquatic

Metabolism (PT

- 1

- 4) 48910702 9.4% (29 d) 5.7% (100 d)

PT

- 1

- 8

5

- (4

- chlorophenyl)

- N

- (4

- hydroxycyclohexyl)

- 4

- methyl

- 2

-

oxo

- thiazolodine

- 3

- carboxamid

SMILES: Field studies (PT

- 1

- 8) 00156892 3.4% (4 w) 1.6% (52 w)

Aqueous Photolysis (PT

- 1

- 8) 48743404 5.7% (14 d) 5.7% (14 d)Page 23 of 64 Code Name/ Synonym Chemical Name and Available

Fate Data Chemical Structure Study Type Ref.

(MRID) Maximum %AR (day) Final %AR (study length)

C1=C(C=CC(=C1)C2C(C)N(C(S2)

=O)C(NC3CCC(CC3)O)=O)Cl Aerobic Aquatic

Metabolism (PT

- 1

- 8) 48910702 8.1% (29 d) 6.4% (100 d)

PT

- CY

- O (mixture of PT

- 1

- 5

and PT

- 1

- 9) PT

- 1

- 5

5

- (4

- chlorophenyl)

- 4

- methyl

- 2

-

oxo

- N

- (3

- oxocyclohexyl)thiazolodine

- 3

- carboxamide

SMILES: C1=C(C=CC(=C1)C2C(C)N(C(S2)

=O)C(NC3CC(CCC3)=O)=O)Cl Hydrolysis

22 ° C 00141516 ND ND

Aq. photolysis 00146538 0.8% (210 m) 0.8% (300 m)

Aerobic soil 00141515 16.2% (7 d) 0.9% (100 d)

Anaerobic Aquatic

Metabolism 48743405 7.0% (360 d) 7.0% (360 d)

Field studies (PT

- 1

- 5) 00156892 10.5% (26 w) 9.2% (52 w)

PT

- 1

- 9

5

- (4

- chlorophenyl)

- 4

- methyl

- 2

-

oxo

- N

- (4

- oxocyclohexyl)thiazolodine

- 3

- carboxamide

SMILES: C1=C(C=CC(=C1)C2C(C)N(C(S2)

=O)C(NC3CCC(CC3)=O)=O)Cl

K OC : 643 mL/g o.c. (MRID 48743402) Field studies (PT

- 1

- 9) 00156892 10.3% (4 w) 2.5% (52 w)

Aqueous Photolysis 48743404 3.8% (28 d) 3.8% (28 d)

Aerobic Aquatic

Metabolism 48910702 13.1% (29 d) 4.7% (100 d)

Aerobic Soil

Metabolism 48743403 14.4% (31 d)) 4.7% (153 d)

Aerobic soil 00141515 50.2% (70 d) 48.2% (84 d)

Field studies 00156892 35.3% (26 w) 22.4% (52 w)

Aerobic soil 00141515 ND ND

Carbon dioxide Carbon dioxide

Formula: CO 2 MW: 44.1 g/mol O O Hydrolysis 00141516 ND ND

Aerobic soil 00141515 18.9% (84 d) 18.9% (84 d)

ND means “not detected”. NA means “not analyzed”.Page 24 of 64 Table 5 lists the environmental fate properties of hexythiazox, along with the major and minor degradates detected in the submitted environmental fate and transport studies

.

Table 5 . Summary of Hexythiazox Environmental Fate Properties

Study Value (units) Major Degradates Minor Degradates MRID # Study Status and

Comments

Hydrolysis Stable None 00141516 Supplemental

Solubility 0. 12 ppm 44006301 Supplemental

Vapor pressure 1 x 10 - 8 mm Hg 44006301 Supplemental

K OW 337 143533 Supplemental

Direct Aqueous Photolysis t 1/2 = 26.7 days with natural light (TTR) PC

- 1

- 2

PT

- Cy

- O; PT

- Cy

OH; PT

- 1

- 2; PT

- 1

- 3; PC

- 1

- 1; unidentified

. 0014653 9 Supplemental

Aerobic Soil

Metabolism t 1/2 = 70 days (sandy

loam at 25 o C) and 49 days (sandy clay loam) for parent and

UER ;

t 1/2 = 21 days (sandy

loam at 25 o C) and 17 days (sandy clay loam) for parent only PT

- 1

- 2; PT

- Cy

- O

PT

- 1

- 3; PT

- Cy

OH; unidentified. 00141515 Supplemental

- qualitative

due to use of foreign soils

UER were 34.1% to 50.0% of applied by the end of the study. t 1/2 calculations

include UER and total

toxic residues TTR

. Foreign soils were used.

Aerobic Soil

Metabolism UER were not measured from day 0 to day 14.

t 1/2 = 27 days (Wick soil) and 43days (Chuckney soil) from the IORE

model based on inclusion of parent only PT

- 1

- 2; PT

- 1

- 9

PT

- 1

- 3; 48743403 Supplemental

- quantitative

Aerobic Aquatic

Metabolism t 1/2 = 110 days (sandy loam) and 76 days (sand);

t 1/2 calculations include

UER

.

t 1/2 = 43 days (sandy loam) and 30 days (sand);

t 1/2 calculations include parent only

. PT

- 1

- 2; PT

- 1

- 9

PT

- 1

- 3; PT

- 1

- 4;

PT

- 1

- 8 48910702 SupplementalPage 25 of 64 Study Value (units) Major Degradates Minor Degradates MRID # Study Status and

Comments

K d

- ads (mL/g) ;
K oc

- ads (mL/g) 1 6, 30, 32, and 63

- 63.3 mL/g.; 2638 , 3218, 5769,

and 13167 mL/g

oc . No material balance; degradates not analyzed; Japanese soils. PT

- 1

- 2

PT

- Cy

- O; PT

- 1

- 3;

PT

- Cy

- OH; unidentified. 00146544 Supplemental

Terrestrial Field Dissipation t 1/2 = 22 weeks;(DE, silt loam), 19 weeks (NC, sand), 22 weeks (IL, silty clay loam), 40 weeks (CA, sandy loam), 25 weeks (MS, silt loam) field lysimeter study.

Estimate includes toxic

residues but does not

include UER PT

- 1

- 2; PT

- 1

- 9

PT

- 1

- 3; PT

- 1

- 8(cis); PT

- 1

- 4 (trans

- 2); unidentified 00156892 Supplemental

Fish

Bioaccumulation Bioconcentration factor

BCF = 1,000 to 1,600 (whole fish) after 14 days depuration 00152899 Supplemental

3.1.2. Measures of Aquatic Exposure

Aquatic exposures are quantitatively estimated for all of assessed uses using scenarios that represent high exposure sites for hexythiazox use. Each of these sites represents a 10

- hectare

field that drains into a 1

- hectare pond that is 2 meters deep and ha s no outlet. Exposure estimates generated using the standard pond are intended to represent a wide variety of vulnerable water bodies that occur at the top of watersheds including prairie pot holes, playa lakes, wetlands, vernal pools, man

- made and natural ponds, and intermittent and first

- order streams. As a group, there are factors that make these water bodies more or less vulnerable than the standard surrogate pond. Static water bodies that have larger ratios of drainage area to water body volume would b e expected to have higher peak EECs than the standard pond. These water bodies will be either shallower or have large drainage areas (or both). Shallow water bodies tend to have limited additional storage capacity, and thus, tend to overflow and carry pest icide in the discharge whereas the standard pond has no discharge. As watershed size increases beyond 10 hectares, at some point, it becomes unlikely that the entire watershed is planted to a single crop, which is all treated with the pesticide. Headwater streams can also have peak concentrations higher than the standard pond, but they tend to persist for only short periods of time and are then carried

downstream.

Hexythiazox environmental fate data used for generating model parameters are listed in Table 5

. The chemical specific input parameters for the Pesticide Root Zone Model ( PRZM ) and the Exposure Analysis Model System ( EXAMS ) are in Table 6 and use specific input parameters are

in Table 7 ; Chemical property input values were chosen in accordan ce with current inputPage 26 of 64 parameter guidance (USEPA, 2009 3 ) . Application dates were generally set for the crop emergence date in the PRZM scenario . This period is selecte d because hexythiazox is applied to foliage to control target pest s ( e.g ., Bank s grass mi te and spider mites ) that feed on recently emerged leaves and also because more conservative model outputs are generated with early season applications due to increased precipitation. However, mites can occur through a broad portion of a crop year and app lications can therefore occur over a broad range of time (Utah State University Cooperative Extension)

. All uses are modeled assuming aerial application ( i.e.

, 95% application efficiency and 5% spray drift). Parent hexythiazox and UER are included in the calculation of EECs. The contribution of degradates to risk is considered separately but quantified through a toxic equivalency approach.

Table 6 . Summary of PRZM/EX AMS Environmental Fate Data Used for Aquatic Exposure Inputs for Hexythiazox.

Fate Property Value (unit) MRID (or source) Comment

Molecular Weight 352.5 44006301

Henry’s constant 3.87 x 10 - 8 m 3 atm g/mol N/A Calculated from vapor

pressure /solubility

Vapor Pressure 1 x 10 - 8 mm Hg 44006301

Solubility in Water 0. 12 ppm 44006301

Photolysis in Water 17.0 days (parent only) 0014653 9;

Aerobic Soil

Metabolism Half

- lives 114 (parent and UER) 46 days (parent only) 48743403: UER not accounted in first 15 days of study.

Hydrolysis Stable 00141516;

Aerobic Aquatic Metabolism (water column) 145 days (parent and UER) 43 days (parent only) 48910702

Anaerobic Aquatic Metabolism (benthic) Stable 00 146542; unreviewed interim report that does not

achieve DT50 or characterize degradates

K

oc 6188 mL/g

o.c. (parent)

406 mL/g

o.c. (TTR) 00146544
48743402; average Koc value

average Koc value from most mobile degradate,

PT

- 1

- 2

Chemical Application Method (CAM) Foliar application (CAM=2)

All inputs derived with reference to Input Parameter Guidance (Version 2.1; October 22, 2009)

3 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htmPage 27 of 64 A quatic exposure modeling, using PRZM

- EXAMS, was performed to estimate exposures for registered use s of hexythiazox

. The down

- the

- drain model within the Exposure and Fate Assessment Screening Tool ( E

- FAST 4 ; v2.0 ) was used to model exposure from the greenhouse

tomatoes use pattern ( USEPA, 2010 a; D383745 ); however, this greenhouse use pattern resulted in negligible aquatic exp osure relative to the outdoor uses

.

Table 7

. Summary of Use Specific I nputs for PRZM/EXAMS M odeling

4 USEPA. 2013. Council for Regulatory Environmental Modeling. Exposure and Fate Assessment Screening To ol (E

- FAST) version 2.0. http://cfpub.epa.gov/crem/knowledge_base/crem_report.cfm?deid=74903

PRZM Use

Scenario (standard unless noted) Labeled Use represented Application timing Number of Applications Maximum Application

rate, lb

a

. i

. /acre

CA Almond Tree nuts Emergence 1 0.1875

CA Alfalfa Alfalfa, Timothy Emergence 1 0.1875

CA Citrus Citrus Emergence 1 1 0.1875

CA Cotton Cotton Emergence 1 0.156 3

CA Fruit Pome fruit, Stone

Fruit Emergence 1 0.1875

CA Grapes Grapes Emergence 1 0.1875

CA Nursery Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used March 1 date 1 1 0.1875

CA Rangeland Alfalfa, Timothy Maturity 1 0.1875
CA Strawberry Strawberry Emergence 1 1 0.1875

CA Wheat Alfalfa, Timothy Emergence 1 1 0.1875

FL Nursery Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used March 1 date 1 1

FL Peppers Peppers Emergence 1 0.1875
FL Strawberry Strawberry Emergence 1 0.1875

GA Peaches Stone Fruit Emergence 1 0.1875

ID Potato Potato Emergence 1 0.1875

IL Corn Field corn, sweet

corn Emergence 1 0.1875

KS Corn Field corn, sweet

corn Emergence 1 0.1875

KS Sorghum Sorghum Emergence 1 0.1875Page 28 of 64 MI Beans Dry Beans,

Succulent Beans Emergence 1 0.1875

MI Cherry Stone Fruit Emergence 1 0.1875

MI Nursery Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used March 1 app date 1 1 0.1875

MS Corn Field corn, sweet

corn Emergence 1 0.1875

MS Soybeans Dry Beans,

Succulent Beans Emergence 1 0.1875

NC Apple Pome Fruit Emergence 1 0.1875

NC Corn Field corn, sweet

corn Emergence 1 0.1875

ND Wheat Alfalfa, Timothy Emergence 1 0.1875

NJ Nursery Non

- bearing trees, Orchids,

Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used March 1 app date 1 1 0.1875

NY Grapes Grapes Emergence 1 0.1875

OH Corn Field corn, sweet

corn Emergence 1 0.1875

OR Apple Pome Fruit Emergence 1 0.1875

OR Berries Caneberries Emergence 1 0.1875

OR Filberts Tree nuts Emergence 1 0.1875
OR Hops Hops Emergence 1 0.1875

OR Mint Mint Emergence 1 0.156 3

OR Nursery Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used March 1 app date 1 1 0.1875

OR Wheat Alfalfa, Timothy Emergence 1 0.1875

OR Xmas trees Christmas Trees Used March 1 app date 1 1 0.1875

Orchard Dates Emergence 1 0.1875
PA Apple Pome Fruit Emergence 1 0.1875

PA Corn Field corn, sweet

corn Emergence 1 0.1875Page 29 of 64 1 Nursery emergence dates are variable. A March 1 emergence date was selected a s a generic emergence date

Results from each PRZM scenario are presented in Table 8 and the highest representative modeling results for each use category is presented in Table 9

. Output that generates peak EECs are reported in Appendix 1

.

Table 8 . Tier II Concentrations of Hexythiazox and U nextracted R esidue in Surface W ater TN Nursery Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental

shrubs and vines Used 3

- 1 app date 1 1 0.1875

TX Alfalfa Alfalfa, Timothy Emergence 1 0.1875
TX Grapefruit Citrus Emergence 1 0.1875
TX Sorghum Sorghum Emergence 1 0.1875

PRZM Use

Scenario (standard unless noted) Peak (μg/L) 21

- day

average (μg/L) 60

- day

average (μg/L)

CA Alfalfa 1.03 0.74 0.64

CA Almond 1.18 0.88 0.78

CA Citrus 0.87 0.57 0.47

CA Cotton 0.9 0.64 0.57

CA Fruit 0.98 0.68 0.58
CA Grapes 0.94 0.65 0.54
CA Nursery 1.67 1.21 1.03
CA Rangeland 0.97 0.69 0.59
CA Strawberry 1.55 1.24 1.15

CA Wheat 1.97 1.66 1.6
FL Nursery 1.62 1.13 1.05
FL Peppers 1.9 1.51 1.34
FL Strawberry 1.28 1.01 0.9

GA Peaches 1.13 0.8 0.7

ID Potatoes 1.45 1.14 1.05

IL Corn 3.77 3.27 3.06

KS Corn 2.37 2.04 1.91
KS Sorghum 2.82 2.44 2.29

MI Beans 1.87 1.59 1.47
MI Cherry 2.15 1.88 1.77
MI Nursery 1.65 1.35 1.25

MS Corn 5.35 4.02 3.44
MS Soybeans 2.54 1.95 1.84

NC Apple 1.62 1.32 1.21

NC Corn 2.32 1.8 1.65Page 30 of 64 Table 9

. Peak EECs for Use P attern Categories

. Scenario from which EECs are derived

are in bold

Scenarios Uses Peak (μg/L) 21

- day average (μg/L) 60

- day average (μg/L)

IL Corn

KS Corn

MS Corn

NC Corn

OH Corn

PA Corn Corn 5.35 4.02 3.44

CA Grapes NY Grapes Grapes 4.14 3.57 3.47

KS Sorghum TX Sorghum Sorghum 3.66 2.73 2.47

MS Soybeans

MI Beans Dry Beans, Succulent

Beans 2.54 1.95 1.84

CA Fruit

GA Peaches MI Cherry Stone Fruit 2.15 1.88 1.77

OR Wheat

CA Alfalfa CA Rangeland

CA Wheat

ND Wheat

TX Alfalfa Alfalfa, Timothy,

Ornamental Lawns and Turf, Non

residential Turf 1.97 1.66 1.6

FL Peppers Peppers 1.9 1.51 1.34 CA Nursery FL Nursery MI Nursery NJ Nursery Non

- bearing trees, Orchids, Christmas Trees, Ornamental

non

- flowering plants, 1.82 1.54 1.43 ND Wheat 1.65 1.37 1.27
NJ Nursery 1.82 1.54 1.43
NY Grapes 4.14 3.57 3.47

OH Corn 3.12 2.63 2.37
OR Apple 1.25 0.94 0.84

OR Berries 1.37 1.07 0.96

OR Filberts 1.25 0.95 0.85

OR Hops 1.32 1.02 0.91

OR Mint 1.04 0.79 0.7
OR Nursery 1.22 0.93 0.82

OR Wheat 1.69 1.39 1.29

OR Xmas trees 1.14 0.84 0.74

Orchard 1.38 1.06 0.98
PA Apple 1.6 1.3 1.21

PA Corn 2.3 2.04 1.9
TN Nursery 1.75 1.45 1.35

TX Alfalfa 1.32 1 0.92
TX Grapefruit 1.1 0.79 0.7
TX Sorghum 3.66 2.73 2.47Page 31 of 64 OR Nursery TN Nursery Ornamental shrubs

and vines

CA Fruit NC Apple OR Apple PA Apple Pome Fruit 1.62 1.32 1.21

CA Strawberry FL Strawberry Strawberry 1.55 1.24 1.15

ID Potatoes Potatoes 1.45 1.14 1.05

Orchards Dates 1.38 1.06 0.98

OR Berries

CA Fruit Caneberries 1.37 1.07 0.96

OR Hops Hops 1.32 1.02 0.91

OR Filberts

CA Almond Tree nuts 1.25 0.95 0.85

OR Xmas Trees Christmas Trees 1.14 0.84 0.74

OR Mint Mint 1.04 0.79 0.7

CA Cotton Cotton (CA) 0.9 0.64 0.57

This assessment does not include degradates, PT

- 1

- 2, PT

- 1

- 3, PT

- 1

- 4, PT

- 1

- 8, and PT

- 1

- 9 in the

calculation of EECs. However, risk from degradates is considered outside the calculation of RQs by accounting for degradat e toxicity relative to hexythiazox, occurrence in environmental fate studies, and degradate mobility relative to hexythiazox. Degradates are estimated to be 2% to 14% as toxic as parent hexythiazox, depending on taxon and the specific degradate. Degradate toxicity is characterized in Appendix 3 through the use of ECOSAR. Further, maximum degradate occurrences in environmental fate studies range from 9% to 40% of applied radioactivity. Finally, degradates are more mobile than hexythiazox with parent K OC eq ualing 6,188 mL/g o.c. and the most mobile degradate K OC equaling 406 mL/g o.c. Multiplying the relative toxicity of degradates and maximum occurrences in environmental fate studies and adjusting by the increased degradate mobility provides a conservative estimate of degradate

contribution to risk. Multiplying the relative toxicity of degradates and maximum occurrences in environmental fate studies yields an increased effective exposure of 4%. Replacing the hexythiazox K OC with the degradate K OC in a sam ple of PRZM/EXAMS scenarios yields two to three times larger EECs. Therefore, the increased effective exposure presented by degradates is 8% to 12%. This uncertainty can be added to exposure estimates for characterization of RQs

Just as the inclusion of d egradates should be characterized, so should the exclusion of UERs from the reporting of EECs. Though conservative, there is uncertainty in the inclusion of these residues. Exclusion of UER from aquatic exposure modeling reduces EECs by 47%, on average.

This exclusion is characterized in further detail in Table 10

.Page 32 of 64 Table 10

. EEC Perc ent Reduction upon E xclusion of UERs

Uses Average

reduction in

EEC for Parent Only Uses Average

reduction in

EEC for Parent Only

Corn 43 Strawberry 41 Peppers 46 Tree nuts 4 2 Dry Beans,

Succulent Beans 50 Hops

4 5 Sorghum 33 Caneberries 4 6 Alfalfa, Timothy,

Ornamental Lawns and Turf, Non

residential Turf 53 Citrus (CA, AZ, TX)

56 Grapes 50 Christmas Trees 38

Dates 49 Mint 43

Non

- bearing trees, Orchids, Christmas Trees,

Ornamental non

flowering plants,

Ornamental shrubs

and vines 38 Cotton (CA)

39

Stone Fruit 56 Potato 47

Pome Fruit 48

Data in Table 6 indicate that the maximum surface water EECs for total residues of hexythiazox

were generated with the Mississippi ( MS ) Corn scenario and are as follows:

5.35 μg/L for the 1 in 10 year annual peak concentration

4.02 μg/L for the 21

- day average concentration

3.44 μg/L for the 60

- day average concentration

Benthic pore water concentrations are used to assess exposure to aquatic benthic invertebrates. Benthic pore w ater concentrations for the scenario with maximum surface water exposure ( MS

Corn ) are:

3.21 μg/L for the 1 in 10 year annual peak concentration

3.20 μg/L for the 21

- day average concentration

3.19 μg/L for the 60

- day average concentration

The characterization of residues is of great importance in environmental fate studies. If degradates are excluded from fate parameters, EECs are reduced by 33% to 56%

. ThisPage 33 of 64 difference and the uncertainty associated with the data in the environmental fat e data relevant to

UER is critical limitation in this assessment. UER bioavailability is a key missing element in this assessment which additional data could clarify.

3.1.3. Measures of Terrestrial Exposure

3.1.3.1. Terrestrial Animals

Ingestion of Food Items Based on Foliar Application

Exposure estimates for terrestrial animals assumed to be in the target area or in an area exposed to spray drift are derived using the T

- REX 5 model (version 1. 5.1., 10/12/2012 ). This model incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is based on a large set of actual field residue data. The upper limit values from the nomograph represent an approximation of the highest residue value observed in the data set (Hoerger and Kenaga 1972). Consideration is given to different types of feeding strategies for mammals and birds, including herbivores, insectivores and granivores. For dose

- based exposures, three we ight classes of birds (20, 100, and 1000 g) and mammals (15, 35

, and 1000 g) are considered. Given that no data on interception and subsequent dissipation from foliar surfaces are available for hexythiazox , a default foliar dissipation half

- life of 35 days is used based on the work of Willis and McDowell (1987). The same hexythiazox application and seasonal rate limitations as evaluated in previous

assessments ( i.e

., a maximum application rate of 0.1875 lb a.i. and one application per year ) are taken from active labels and are used to estimate terrestrial exposure for this assessment. The dietary

- based EECs on a variety of food items from the use of hexythiazox applied at the

maximum label rate is provided in Table 11 ; dose

- based EECs are provided in Table 12

.

Table 11 . T

- REX Calculated Dietary

- Based EECs of Hexythiazox on Food Residues.

Food Type Maximum Dietary

- based EECs (mg/kg)

Short Grass 45.00

Tall Grass 20.63
Broadleaf plants 25.31
Fruits/pods/ seeds 2.81
Arthropods 17.63

5 USEPA. 2013. Pesticides: Science and Policy. Terrestrial Models, T

- REX Vers ion 1.5/1. http://www.epa.gov/oppefed1/models/terrestrial/Page 34 of 64 Table 12 . T

- REX Calculated Dose

- Based EECs of Hexythiazox Uses on Terrestrial Food Residues.

Food Type Dose

- based EECs (mg/kg

- bw) (birds) Dose

- based EECs (mg/kg

- bw) ( mammals)

Small (20 g) Medium (100 g) Large (1000 g) Small ( 15 g) Medium ( 35 g) Large (1000 g) Short grass 51.2 29.2 13. 1 42.9 29.6 6.88 Tall grass 23. 5 13. 4 6.00 19. 7 13. 6 3.15 Broadleaf plants 28.8 16.4 7.36 24.1 16. 7 3.87 Fruits/pods 3.20 1.83 0.82 2.68 1.85 0.43 Arthropods 20. 1 11.4 5.12 16.8 11.6 2.69 Seeds (granivore) 0.71 0.41 0.18 0.60 0.41 0.10

3.1.3.2. Terrestrial Plants

Hexythiazox exposure to terrestrial and semi

- aquatic plants i s estimated using the TerrPlant 6

( v ersion 1.2. 2 ) model. The model generates EECs for plants residing near a use area that may be exposed via runoff and/or spray drift. The EECs are generated from one application at the maximum rate for a particular use and compound

- specific solubility information. Only a single application is considered because it is assumed that for plants, toxic effects are likely to manifest shortly after the initial exposure and that subsequent exposures do not contribute to the response. Hence, the model estimates EECs based on application rate, the solubility factor

, and d efault assumptions of drift. The EECs for terrestrial and semi

- aquatic plants for a single application of hexythiazox at the maximum label rate are presented in Table 13

.

Table 13. EECs for Terrestrial and Semi

- Aquatic Plants Near Hexythiazox Use Areas.

Single Max. Application Rate (lbs a.i./A) EECs (lbs a.i./A) (Ground Spray, Aerial Spray)

Total Loading to Adjacent Dry Areas (sheet runoff + drift) Total Loading to Semi

Aquatic Areas (channelized runoff + drift) Drift EEC

Ground spray Aerial

spray Ground

spray Aerial

spray Ground

spray Aerial

spray
0.1875 0.003 8 0.011 3 0.020 6 0.028125 0.001875 0.009375

3.2. Ecological Effects Characterization

The ecological effects characterization for hexythiazox is based on data generated from guideline studies submitted by the registrant and from open literature studies in the ECOTOX database (http:/www/epa.gov/ecotox).

6 USEPA. 2013a. Pesticides: Science and Policy. Terrestrial Models, TerrPlant Version 1.2.2. http://www.epa.gov/oppefed1/models/terrestrial/Page 35 of 64 A brief description of available aquatic and terrestrial toxicity data used to calculate RQs is provided below in Sections 3.2.1 and 3.2.2

. As noted in Section 3.2.3, there are currently no reported ecological incidents involving hexythiazox

.

3.2.1. Aquatic Effects Characterization 7

Aquatic toxicity data fo r animals and plants are summarized in Table 1 4

. For freshwater and

estuarine/marine fish and invertebrates

, the acute toxicity of the compound (in terms of an LC 50 )

is l imited by its solubility

, i.e ., 0.12 mg/L, as none of the studies were able to establish a

definitive LC 50

. On a chronic exposure basis, hexythiazox result ed in decreased growth (length and weight), survival , and production of young water fleas ( Daphnia magna ) and decreased growth (length) and production of young estuarine/marine shrimp ( Americamysis bahia ) with

NOAEC values for freshwater and estuarine/marine invertebrates a t 6.1 ppb and 8.88 ppb, respectively. Chronic toxicity data are not available for either freshwater or estuarine/ marine

fish. EFED has determined that it would not be appropriate to derive an Acute

- to

- Chronic Ratio to generate chronic values for freshwater and estuarine/marine fish from the acute endpoints given that the acute endpoints for these taxa a re non

- definitive.

Aquatic vascular and nonvascular plants were not found to be sensitive to hexythiazox at the

concentrations tested . The 14

- day EC 50 for the vascular aquatic plant duckweed ( Lemna gibba)

was > 120 μg a.i. /L. Data were available for on ly one non

- vascular aquatic plant species, the freshwater green algae Desmodesmus subspicatus

, with a 96

- hr EC 50 of >120 μg a.i./L and

NOAEC of 25 μg a.i. /L , based on statistically significant reductions in chlorophyll a in comparison to the negative control.

7 Readers Note: Much of the original toxicity data cited in previous ecological risk assessments for hexythiazox were deemed acceptable. However, a more recent review of these data found that several of the studies had hexythiazox concentrations that were above solubility (solubility under specific test conditions is unknown) and water samples were not centrifuged or alternatively filtered prior to processing and analysis. Additiona lly, dissolved hexythiazox concentrations were not stable and in several acute studies; final concentrations had declined to 10%

- 70% of initial concentrations. These issues were not identified in the initial reviews and the studies were subsequently downg raded (USEPA, 2011, D364594). Rationale for each study reclassification is provided in Appendix 2.Page 36 of 64 Table 14. Summary of Most Sensitive Acute and Chronic Toxicity Data for Aquatic Animals Exposed to Hexythiazox.

Species Acute Toxicity Chronic Toxicity

96

- hr

LC 50 /EC 50 (μg a.i./L) 48

- hr EC 50 (μg a.i ./L) Toxicity

Classification (MRID) NOAEC/

LOAEC (μg a.i./L) Endpoints (MRID)

Rainbow trout ( Oncorhynchus mykiss) > 120

-- Highly Toxic 1

(00260839) NA

--
Bluegill sunfish ( Lepomis macrochirus ) > 120

-- Highly Toxic 1

(00260839) NA

--

Waterflea ( Daphnia magna ) -- -- No data 6.1/12.7 Survival (43944701) Sheepshead minnow ( Cyprinodon variegatus ) > 120

-- Highly Toxic 1

( 47315801) NA

--

Mysid shrimp (Americamysis bahia ) -- > 110 2 Highly Toxic 1

(47450601) 8.89/17.2 F 0 & F 1 male length (48114001)

Duckweed ( Lemna gibba ) -- 7

- day EC 50 > 120 (47450602) 120 / >120 N A (47450602) Green algae toxicity ( Desmodesmus subspicatus ) -- 72

- hr EC 50 > 120 ( 48910703 ) 25 N A ( 48910706 )

1 A lthough the compound is technically classified as highly toxic, no mortality was observed up to the practical solubility limit of the compound in water; therefore, the toxicity of the compound appears to be limited by its solubility.

2 This value is slightly less than the solubility value reported in Table 4 , but is based on measured concentrations

. F ilters were used to prevent undissolved test substance from entering the test vessels and final measured values were equal to initial measured values for this study

. NA = Not available

EFED attempted to estimate the chronic toxicity of hexyt hiazox to fish based on the use of quantitative structure

- activity relationships (QSARs) for structurally similar chemicals , using

ECOSAR 8 v1. 11

. A ll four QSAR classes (thiazolidinones, monothiocarbamates, carbonyl ureas,

and neutral organics) returned acute toxicity estimates above 120 μg/L (but less than three times greater than the solubility limit of hexythiazox). Quantitative use of the measured daphnia chronic endpoint is supported by the range of chronic freshwater inv ertebrate QSARs which

bracket the 6.1 μg/L value. This boosts confidence in the reliability of the QSAR approach for taxa for which hexythiazox toxicity data are not available. The fish chronic endpoints ranged

from 3 to 26 μg/L ( Table 15 ) . The value of 3 μg/L (carbonyl urea class) is the most conservative estimate, and it is quantitatively similar to the measured data for invertebrate chronic effects (6.1 μg/L for d aphnia). There is good agreement between the experimentally derived freshwater aquatic i nvertebrate acute toxicity endpoint for hexythiazox transformation product PT

- 1

- 2 with the QSAR estimate for the monothiocarbamate class (17,600 μg/L versus 41,700 μg/L). The excellent agreement between the experimentally derived freshwater aquatic invertebrate chronic toxicity endpoints (hexythiazox parent) with the QSARs for the monothiocarbamate class further supports the use of chronic daphnid QSAR data for the monothiocarbamate class to characterize the chronic risk of hexythiazox transf ormation products

to freshwater aquatic invertebrates ( Table 16 )

.

8 USEPA 2012. Ecological Structure Activity Relationships (ECOSAR) version 1.11. http:// www.epa.gov/oppt/newchems/tools/21ecosar.htmPage 37 of 64 Table 15. Hexythiazox Parent Data (Empirical) and QSAR Estimates by Class QSAR class Fish acute (μg/L) Fish chronic (μg/L) Daphnia

chronic (μg/L)
(EFED data) >120 No data 6.1

Thiazolidinones 326. 6. 17.

Monothiocarbamates 423. 12. 6. Carbonyl ureas 440. 3. 4. Neutral Organic 179. 26. 35.

Table 16

. Chronic Daphnia Toxicity QSAR Endpoints Estimates for Hexythiazox Parent

and Transformation Products

C hemical Endpoint (μg/L) T hiazoldinones (μg/L) M onothiocarbamates (μg/L) C arbonylureas (μg/L) Neutral (μg/L)

P arent 6

. 1 17 6 4 35

PT

- 1

- 2 no data 664 138 81 2,921

PT

- 1

- 3 no data 485 103 n/a 2,075

PT

- 1

- 4 no data 163 43 41 509

PT

- 1

- 5 no data 337 80 87 1,218

PT

- 1

- 8 no data 163 43 41 509

PT

- 1

- 9 no data 337 80 87 1,218

3.2.2. Terrestrial Effects Characterization

Toxicity values for terrestrial animals and plants are summarized in Tables 1 7 and 1 8

, respectively

. H exythiazox is practically non

- toxic to mammals, birds (and to reptiles and

terrestrial

- phase amphibians for which birds serve as surrogates) , and honey bees ( Apis mellifera ) on an acute exposure basis. No sublethal effects were observed in either the acute bird

or mammalian studies. In chronic mammalian st udies, no treatment

- related effects were observed in the rat ( Rattus norvegicus ) at the concentrations tested (up to 2400 ppm). A chronic avian reproduction study conducted with the northern bobwhite quail indicates significant

treatment

- related effects o n food consumption at mean

- measured concentrations of 297 mg/kg

diet, resulting in a NOAEC of 100 mg a

. i

. /kg

- diet. H igh coefficients of variation, ranging

between 42 and 53% for eggs laid per pen, and 62 and 89% for male weight gain , likely limited the po wer of the statistical analysis to detect an effect for these variables. On an acute exposure basis, hexythiazox is classified as ‘practically nontoxic’ to non

- target terrestrial insects including young adult honey bees (honeybee acute contact LD 50 > 200 μ g a

. i

. /bee). A review of the open literature found two studies (MRID 47875304, E90553) that confirmed the lack of acute toxicity of hexythiazox to bumblebees ( Bombus spp

. ) and honey bees, respectively. However, given the mode of action for hexythiazox as an ovicide/growth inhibitor on eggs and larval mites and that

chronic effects

— including reduced reproduction

— were observed in both the freshwater andPage 38 of 64 estuarine/marine invertebrate life cycle tests, the re is potential for chronic risk to terrestrial invertebrates, including beneficial insects.

Tier I seedling emergence testing was conducted with the technical grade active ingredient ( TGAI ) , rather than the typical end

- use product ( TEP ) as required by the non

- target plant protection data requirements specified in OCSPP 850.4100

. Two species, onion and oilseed rape (application rates of 0. 21 and 0. 16 lb a.i./A , respectively)

, exhibited inhibitions in excess of 25% for seedling emerg ence (MRID 47433305) which triggers Tier II testing , although no Tier II tests

were submitted. Tier I vegetative vigor testing with TGAI noted significant differences between solvent and negative controls for cabbage shoot length and lettuce dry weight; h owever, there did not appear to be any adverse effect of treatment on these endpoints. Tier I Vegetative Vigor testing with a hexythiazox TEP (MRID 48910704) , while only available for six species,

determined no significant reduction in biomass compared to the negative control at an application rate of 0.223 lb a.i./A, which is above the maximum label rate

. While data are only

available to assess risk to six species (OCSPP 850.4150 requires testing of 10 crop species),

a vailable data indicate t hat hexythiazox is not expected to significantly impact the vegetative vigor of terrestrial plants.

A review of the open literature found one study relating to terrestrial plants in the ECOTOX database (E090553, Mayer & Lunden, 1986)

. The study authors fo und that applications of

he xythiazox at a rate of 0.249 lb a.i./acre decrease d the pollen viability of apples and pears. However, the authors note that this was above the maximum labeled rate , a lower application at

0.125 lb a.i./acre had no effect, and t hat hexythiazox is unlikely to be applied during bloom (although EFED notes that labels do not prohibit applications during bloom)

.

Table 1 7

. Hexythiazox Terrestrial Animal Toxicity Summary

Parameter Study Type Species Exposure

Duration Toxicity

Value Reference (Study Classification)

1. Abundance ( i.e ., survival, reproduction, and growth)

of individual

birds 1a. Acute (Dose

based) Mallard duck ( Anas platyrhynchos ) Single oral

dose >2510 mg/kg bw

(LD 50 ) 072940 (acceptable)

1b. Acute (Dietary

based) Northern

Bobwhite ( Colinus virginianus ) &

Mallard duck ( Anas platyrhynchos ) 8

- Day dietary >5620 mg/kg diet (LC 50 ) 072940 (acceptable)

1c. Chronic (Dietary

based) Northern

bobwhite ( Colinus virginianus ) Avian reproduction study 100 mg ai/kg diet 48609401 (acceptable)

2. Abundance ( i.e ., survival, 2a. Acute Rat ( Rattus norvegicus ) Single oral

dose >5,000 mg/kg bw 072941 (acceptable)Page 39 of 64 Parameter Study Type Species Exposure

Duration Toxicity

Value Reference (Study Classification) reproduction, and growth)

of individual

mammal (LD 50 )

2b. Chronic Rat ( Rattus norvegicus ) 2

- Generation reproduction study > 2400 mg/kg diet (NOAEL) 00147578 (acceptable)

3. Survival of

beneficial

insects 3a. Acute

Contact Honey Bee ( Apis mellifera ) 48 hours > 200

μ g/bee 072939 (acceptable)

Table 18

. Summary of Tier I Terrestrial Plant Toxicity Data for Hexythiazox

Crop Species EC 25 (lbs a.i./A) NOAEC (lbs a.i./A) Most sensitive
parameter MRID

Seedling Emergence

Monocots Oat >0. 16 0.1 6 NA 48211801 Ryegrass >0. 21 0. 21 NA 47433305

Corn >0. 1 6 0.1 6 NA 48211801

Onion <0. 21 < 0

. 21 Emergence 47433305

Dicots Oilseed rape <0. 19

<0.16 < 0.19

<0.16 Emergence, shoot length 47433305

48211801 Soybean >0

. 21 0

. 21 NA 47433305

Radish >0. 16 0.1 6 NA 48211801

Tomato > 0. 21 0. 21 NA 47433305

Cucumber > 0. 21 0. 21 NA 47433305

Bean >0.1 6 0.1 6 NA 48211801 Vegetative Vigor

Monocots Oat >0.19 0.19 NA 47433306 Ryegrass >0.19 0.19 NA 47433306

Corn >0.19 0.19 NA 47433306

Onion >0.19 0.19 NA 47433306

Dicots Soybean >0.19 0.19 NA 47433306 Oilseed rape >0.19 0.19 NA 47433306

Tomato >0.19 0.19 NA 47433306

Cucumber >0.19 0.19 NA 47433306 Cabbage >0.17 0.17 NA 47433306

Lettuce >0.17 0.17 NA 47433306

3.2.3. Review of Incident Data

A review of the Environmental Incident Information System (EIIS

, version 2.1 ) database , which is maintained by the Agency’s Office of Pesticide Programs, and the Avian Monitoring Information System (AIMS), which is maintained by the American Bird Conservancy, for ecological incidents involving hexythiazox was completed on March 1, 2013

. The results o f this

review show no reported incidents.Page 40 of 64 However, b ecause of limitations in the incident reporting system, the lack of incident reports cannot be construed as the absence of incidents from the registered use of hexythiazo x

. Reporting by states is only voluntary, and individuals discovering incidents may not be informed on the procedure of reporting these occurrences. Additionally, much of the se database s are generated from registrant

- submitted incident reports. In addition, incident reports for non

- target organisms typically provide information only on mortality events and plant damage incidents. Impacts to non

- commercial beneficial insects and other inverteb rates are not likely to be reported. Except for phytotoxic effects in terrestrial plants, sublethal effects for organisms such as reduced growth or impaired reproduction are rarely reported. Because of these logistical difficulties, EIIS is most likely a minimal representation of all pesticide

- related ecological

incidents and the absence of incident reports cannot be construed as the absence of incident s

.

4. Risk Characterization

4.1. Risk Estimation

4.1.1. Aquatic Organisms

The peak EEC s in surface water generated from the PRZM/EXAMS model represents acute exposure to fish, aquatic invertebrates, and aquatic plants, and the highest 21

- day and 60

- day average EEC s represents chronic exposure to aquatic invertebrates and fish

, respectively

. Acute and chronic RQs for fresh water and estuarine/marine animals are summarized in Table 1 7 . RQs

for aquatic vascular and nonvascular plants are presented in Table 1 8

.

4.1.1.1. Aquatic Animals

Fish

Acute RQs were not calculated for freshwater or estuarine/marine fish because the acute studies

showed no effect at the limit of solubility ( Table 1 7 )

.

No data were available to assess chronic risk to freshwater or estuarine/marine fish; however, a QSAR approach was employed which estima ted chronic fish endpoint s ranging from 3 to 26 μg/L for carbonyl urea and neutral organic class es, respectively

. Under the most conservative exposure scenario and residue assumptions ( i.e. , MS corn assuming UER), chronic exposure estimates are greater than the predicted chronic toxicity endpoint

. Conversely, t he least sensitive QSAR endpoint is greater than all estimated chronic exposure concentrations

, but by less than an order of magnitude. The addition of 8% to 12% additional risk from the degradat e toxic equivalency approach has no affect on exceedances of the LOC.

Aquatic invertebrates

Acute hexythiazox RQs could not be calculated for freshwater invertebrates because no data

were available , and were not calculated for estuarine/marine invertebra tes because no effect sPage 41 of 64 were recorded at the limit of solubility

. Data concerning the acute toxicity of hexythiazox transformation products PT

- 1

- 2, PT

- 1

- 3, and PT

- 1

- 9 to freshwater aquatic invertebrates are available; PT

- 1

- 2 acute toxicity to daphnids is 1 7,600 μg/L, more than three orders of magnitude greater than peak EECs, and PT

- 1

- 3 and PT

- 1

- 9 are not acutely toxic at their respective solubility

limits

. Hexythiazox parent c h ronic RQs were calculated for both freshwater and

estuarine/marine invertebrates ; neither freshwater nor estuarine/marine chronic RQs exceed the

LOC (1.0) for any registered hexythiazox use pattern categories ( Table 1 9 )

. For hexythiazox transformation products, chronic daphnid QSA R predictions indicate that chronic endpoints are approximately one to two orders of magnitude greater ( i.e.

, less sensitive) than that of the parent for monothiocarbamates (agreement between the acute and chronic hexythiazox parent empirical data and QSAR data was extremely good for this class). The addition of 8% to 12% additional risk from the degradate toxic equivalency approach has no affect on exceedances of the LOC.Page 42 of 64 Table 1 9 . Summary of Acute and Chronic RQs for Freshwater and Estuarine/Marine Fish and Invertebrates Exposed to Hexythiazox ( Maximum EECs by use pattern

, assuming UER )

Toxicity Value (μg a.i./L) >120

- - - - >110 6.1 8.89

Scenario/Uses App Rate (lb a.i./A) x No.

of Apps Peak EEC (μg

a.i. /L) 21

- day EEC (μg

a.i. /L) Acute FW

and E/M

Fish Chronic

FW and

E/M Fish Acute

FW

Invert Acute E/M

Invert RQ Chronic

FW Invert RQ Chronic

E/M Invert RQ

MS Corn / field corn &

sweet corn

0.1875 x 1 5.35 4.02NOT TOXIC AT SOLUBILITY LIMITNO DATANO DATANOT TOXIC AT SOLUBILITY LIMIT 0.66 0.45
NY Grapes / Grapes 4.14 3.57 0.59 0.40
TX Sorghum / Sorghum 3.66 2.73 0.45 0.31 MS Soybeans / Beans, dry

and succulent 2.54 1.95

0.32 0.22
MI Cherry / Stone fruits 2.15 1.88 0.31 0.21

CA Wheat / Alfalfa, timothy, ornamental lawns and turf, non

- residential

turf. 1.97 1.66

0.27 0.19 FL Peppers / Pepper/eggplant subgroup

8

- 10B 1.90 1.51

0.25 0.17 NJ Nursery / Non

- bearing trees, orchids, Christmas trees, ornamental non

flowering plants,

ornamental shrubs and

vines 1.82 1.54

0.25 0.17 NC Apple / Pome fruits:

a pple, crabapple, loquat, mayhaw, pear, oriental pear, quince 1.62 1.32

0.22 0.15 CA Strawberry / Strawberry 1.55 1.24

0.20 0.14

ID Potatoes / Potatoes (OR, WA, &ID only) 1.45 1.14

0.19 0.13

Orchards / Dates 1.38 1.06 0.17 0.12

OR Berries / Caneberries 1.37 1.07 0.18 0.12Page 43 of 64 Toxicity Value (μg a.i./L) >120

- - - - >110 6.1 8.89

Scenario/Uses App Rate (lb a.i./A) x No.

of Apps Peak EEC (μg

a.i. /L) 21

- day EEC (μg

a.i. /L) Acute FW

and E/M

Fish Chronic

FW and

E/M Fish Acute

FW

Invert Acute E/M

Invert RQ Chronic

FW Invert RQ Chronic

E/M Invert RQ

OR Hops / Hops 1.32 1.02 0.17 0.11

OR Filberts / Tree nuts 1.25 0.95 0.16 0.11

OR Christmas trees /

Christmas trees 1.14 0.84

0.14 0.09

OR Mint / Mint

0.1563 x 1 1.04 0.79 0.13 0.09

CA Cotton / Cotton (CA only) 0.90 0.64

0.10 0.07 Generally, numbers were rounded to three significant figures, except for the RQs, for which no more than two decimal places were used. All exposure scenarios modeled aerial application

No LOC exceedances (acute RQ > 0.05; chronic RQ > 1.0, for listed species) were identified

. Acute FW (freshwater) RQ = use

- specific peak EEC / 17,600 μg a.i./L [for water flea

, Daphnia magna ]. Chronic FW RQ = use

- specific 21

- day EEC / 6.1 μg a.i./L [for water flea

, Daphnia magna ].

Chronic E/M (estuarine/marine) RQ = use

- specific 21

- day EEC / 8.89 μg a.i./L [for mysid shrimp

, Americamysis bahia ].Page 44 of 64 4.1.1.2. Aquatic Plants

As shown in Table 20

, RQs for vascular and nonvascular plants do not exceed the listed or non

listed species LOC (1.0) for any of the currently registered uses of hexythiazox , as evidenced by the RQs derived from the most conservative exposure scenario and residue assumptions ( i.e. , MS corn assuming UER) , which do not result in LOC exceedances

.

Table 20 . Acute RQs for Aquatic Vascular and Nonvascular Plants Exposed to Hexythiazox

Application Rate lbs (ai/A (#app/interval) Peak

EECs (ppb) Vascular Aquatic Plant RQs

EC 50 > 120 μg a.i. /L

NOAEC = 120 μg a.i. /L Nonvascular Aquatic Plant RQs

EC 50 > 120 μg a.i. /L

NOAEC = 25 μg a.i. /L

Non

- listed

Species Listed Species Non

- listed Species

0.1875(1) 5.35 < 0. 05 0. 05 < 0. 05

4.1.2. Terrestrial Organisms

4.1.2.1. Birds and Mammals

Ingestion of Food Items Based on Foliar Application

Based on the available toxicity data, no acute mortality and/or sublethal effects were observed in any of the avian or mammalian studies at the highest levels tested. O nly non

- definitive acute and

sub

- acute toxicity endpoints are available for birds and mammals; therefore, non

- definitive a cute RQs are presented in Tables 21 and 2 2

. Further discussion of the predicted exposure values

relative to the levels at which no mortality o ccurred is prov ided as part of the risk description in

Section 4.2.2

. In chronic mammalian studies, no treatment related effects were observed in the Norway rat ( Rattus norvegicus ) at concentrations tested (up to 2400 ppm). O nly a non

- definitive chronic toxicity endpoint is available for mammals and the resulting chronic mammalian dose and dietary based RQs are reported as “less than” values in Table 2 2

. In a chronic avian reproduction study, significant reduction was determined at the 297 mg/kg

- diet treatment lev el compared to the control, resulting in a definitive NOAEC of 100 mg ai/kg

- diet.Page 45 of 64 Table 21 . Acute and Chronic RQs Derived Using T

- REX for Birds, Reptiles and

Terrestrial

- Phase Amphibians Exposed to Foliar Applications of Hexythiazox*

Scenario/ Use s Application Rate (lb a.i./A) x No. of Apps RQs for Birds (20g small bird consuming short grass)

Acute Dose

Based 1 Acute Dietary

Based 2 Chronic Dietary

Based 3

MS Corn / field corn & sweet corn

0.1875 x 1 < 0.04 < 0.01 0.45 MI Beans / Beans, dry and succulent FL Peppers / Pepper/eggplant subgroup

8

- 10B

ND Wheat / Alfalfa, timothy, ornamental lawns and turf, non

residential turf. KS Sorghum / Sorghum NJ Nursery / Non

- bearing trees, orchids, Christmas trees, ornamental

non

- flowering plants, ornamental

shrubs and vines CA Strawberry / Strawberry NY Grapes / Grapes

Orchards / Dates MI Cherry / Stone fruits PA Apple / Pome fruits: a pple, crabapple, loquat, mayhaw, pear, oriental pear, quince

CA Almonds / Tree nuts OR Hops / Hops

OR Berries / Caneberries

ID Potatoes / Potatoes (OR, WA, &ID only)

OR Christmas trees / Christmas trees

OR Mint / Mint 0.1563 x 1 < 0.03 < 0.01 0.38 CA Cotton / Cotton (CA only)

* No LOC exceedances (acute RQ > 0.1 and chronic RQ > 1.0). RQ s calculated using default foliar dissipation half

life of 35 days using T

- REX version 1.5.1.

1 Based on dose

- based EEC and Mallard duck acute oral LD 50 >2510 mg/kg bw

2 Based on dose

- based EEC and Northern bobwhite quail and Mallard duck subacute dietary LC 50 >5620 mg/kg diet

3 Based on dietary

- based EEC and Northern bobwhite quail NOAEC = 100 mg/kg diet.Page 46 of 64 Table 22 . Acute and Chronic RQs Derived Using T

- REX for Mammals Exposed to Foliar Applications of Hexythiaz ox*

Scenario/ Uses Application Rate (lb a.i./A) x No. of Apps RQs for Small Mammals (small [15g] mammals consuming short grass)

Acute Dose

Based 1 Chronic Dose

Based 2 Chronic Dietary

Based 3

MS Corn / field corn & sweet corn

0.1875 x 1 < 0.01 < 0.16 < 0.02 MI Beans / Beans, dry and succulent FL Peppers / Pepper/eggplant subgroup

8

- 10B

ND Wheat / Alfalfa, timothy, ornamental lawns and turf, non

residential turf. KS Sorghum / Sorghum NJ Nursery / Non

- bearing trees, orchids, Christmas trees, ornamental

non

- flowering plants, ornamental

shrubs and vines CA Strawberry / Strawberry NY Grapes / Grapes

Orchards / Dates MI Cherry / Stone fruits PA Apple / Pome fruits: a pple, crabapple, loquat, mayhaw, pear, oriental pear, quince

CA Almonds / Tree nuts OR Hops / Hops

OR Berries / Caneberries

ID Potatoes / Potatoes (OR, WA, &ID only)

OR Christmas trees / Christmas trees

OR Mint / Mint 0.1563 x 1 < 0.01 < 0.14 < 0.02 CA Cotton / Cotton (CA only)

* No LOC exceedances (acute RQ > 0.1 and chronic RQ > 1.0). RQ s calculated using default foliar dissipation half

life of 35 days using T

- REX version 1.5.1.

1 Based on acute dose

- based EEC and Norway rat LD 50 > 5000 mg/kg bw

2 Based on chronic dose

- based EEC and Norway rat LD 50 >5000 mg/kg bw

3 Based on chronic dietary

- based EEC and Norway rat NOAEC >2400 mg/kg diet

4.1.2.3. Terrestrial Invertebrates

On an acute exposure basis, h exythiazox is classified as ‘practically nontoxic’ to non

- target
terrestrial insects including honey bees (honeybee acute contact LD 50 > 200 μg ai/bee). If an RQ

were calculated for terrestrial invertebrates 9 , conservatively assuming the LD 50 to be 200 μg

ai/bee an d the exposure to be the tall grass EEC (20.63 ppm, or 20,630 ppb), the resultant RQ

9 The employed methodology for calculating an RQ was first proposed in the 2012 Pollinator Risk Assessment Framework SAP White Paper, and subsequently validated by the panel. The White Paper is accessible onli ne at regulations.gov, under docket EPA

- HQ

- OPP

- 2012

- 0543Page 47 of 64 would be 103 . This RQ value exceed s the terrestrial invertebrate LOC (0.4) by more than two orders of magnitude.

4.1.2.4. Plants

S ince the most sensitive species (onion and oilseed rape) in the Tier I seedling emergence test experienced significant inhibition at the limit dose, risk to listed and non

- listed plants due to

runoff and spray drift cannot be precluded

. The tested rate in th e submitted studies was 0.21 lb

a.i./acre for onion and 0.16 lb a.i./acre for oilseed rape and the maximum combined EECs due to spray drift and runoff from aerial applications o f hexythiazox range from 0.0113 lb a.i./acre for dry areas to 0.0281 lb a.i. /acre to semi

- aquatic areas. A t the application rates that hexythiazox is applied, the NOAEC for these species would have to be less than 0.03 lb a.i./acre for listed plant species to be at risk. However, since significant inhibition of >25% was exhibit ed at the limit

dose for one

- fifth of tested plant species

, risk to terrestrial plants is uncertain

.

4.2. Risk Description

Hexythiazox is characterized as a persistent compound based on total residues of concern. Although the compound is poorly soluble in water and is considered slightly mobile, its propensity to sorb to organic matter indicates that it can move to surface water through runoff of

sediment

- bound residues (erosion). Further, hexythiazox degradates are moderately mobile and

are more likel y to dissipate through leaching. F ield lysimeter studies combined with data from laboratory degradation studies suggest that residues of the parent compound can remain in soil for protracted periods and not move appreciably in the soil profile.

Additio nally, the compound is characterized as practically nontoxic to terrestrial animals on an acute exposure basis, there is uncertainty regarding its acute toxicity classification for aquatic animals given that only non

- definitive endpoints are available owin g to the limited solubility of the compound. As such, the acute toxicity of hexythiazox may be limited by its solubility. Although chronic effects on survival, growth, and reproduction were recorded in freshwater and

estuarine/marine invertebrates, no data are available to characterize chronic toxicity in fish.

The results of this screening

- level risk assessment indicate that the registered use s of hexythiazox do not have the potential to cause direct adverse acute effects to freshwater and

estuarine/marine fish and invertebrates. Chronic effects to listed and non

- listed species of pelagic freshwater and estuarine/marine invertebrates are not predicted; however, chronic risk to

sediment

- dwelling aquatic invert ebrates is uncertain. C hronic effects to freshwater and

estuarine/marine fish for all hexythiazox use patterns are uncertain

. Hexythiazox is not acutely toxic to avian or mammalian species, nor do data indicate likelihood of chronic effects to

mammals. Chronic effects to birds were identified only at dietary concentrations exceeding the maximum EEC; thus chronic avian risk is considered low . Risk to terrestrial plants is uncertain

because of effects greater than 25% in Tier I studies for terrestrial pla nt see dling emergence. Therefore, this analysis ( i.e. , the preliminary registration review risk assessment) failed to reject

the risk hypothesis [... the registered uses of hexythiazox have the potential to reduce survival, reproduction, and/or growth in lis ted and non

- listed terrestrial and aquatic organisms ]

.Page 48 of 64 4.2.1 . Risks to Aquatic Organisms

For freshwater and estuarine/marine fish and invertebrates

, the acute toxicity of hexythiazox (in

terms of an LC 50 ) is limited by its solubility ( i.e

., 0.120 m g/L) as none of the studies were able to

establish a definitive LC 50 . Therefore, a cute risk to fish and aquatic invertebrates is considered unlikely

.

Chronic risk to listed and non

- listed freshwater and estuarine/marine fish is uncertain for all hexythiazox use patterns in the absence of data; however, our QSAR analysis provides additional resolution, indicating that toxicity bracket s the chronic EEC when exposure includes the UER uncertainty, and that toxicity is greater than the EEC for all use patterns when excluding UER. Inclusion of degradate using the toxic equivalency approach does not impact exceedances of the

LOC. U nder the most conservative exposure scenario and residue assumptions, chronic exposure estimates a re greater than the predicted chronic toxicity endpoint

. Conversely, the least sensitive QSAR endpoint is greater than all estimated chronic exposure concentrations

, but by less than an order of magnitude. Thus, chronic risk to freshwater and estuarine/m arine fish for the most conservative exposure and residue assumptions cannot be precluded

.

Chronic effects to listed and non

- listed species of pelagic freshwater and estuarine/marine invertebrates are not predicted (RQs are less than the chronic LOC of 1.0 for all hexythiazox uses); however, chronic risk to sediment

- dwelling aquatic invertebrates is uncertain. Although some of the triggers for requiring chronic sediment toxicity testing described within CFR 40 part 158.630 are met (e.g., Koc ≥ 1000, sed iment half

- life > 10 days), since a 21

- day toxicity test with midges ( Chironomus riparius ) found no effect to either emergence or development rate at concentrations tested up to hexythiazox’s solubility limit (0.120 mg/L) and peak benthic pore

water EECs a re 3.21 μg/L, the Agency consider s the predicted exposure to be in significant. The NOAEC for benthic invertebrates would have to be below 3.21 μg/L (nearly two times more sensitive than the freshwater pelagic invertebrate growth NOAEC , and eight times more sensitive than the reproduction NOAEC ) to trigger an LOC exceedance. By these lines of

evidence , chronic effects to sediment

- dwelling aquatic invertebrates are uncertain, although the potential for risk is considered to be low

.

Ecotoxicology data for hexythiazox transformation products are only available for freshwater aquatic invertebrates exposed to PT

- 1

- 2, PT

- 1

- 3, and PT

- 1

- 9 on an acute basis . These studies

indicate that the acute risk profile of hexythiazox transformation products is low ; PT

- 1

- 2 acute toxicity to daphnids is 17,600 μg/L, more than three order s of magnitude greater than peak

EECs , and PT

- 1

- 3 and PT

- 1

- 9 are not acutely toxic at the ir respective solubility limits

. The chronic risk profile of hexythiazox transformation products is uncertain, although chronic daphnid QSAR predictions indicate that NOAECs are approximately one to two orders of magnitude less sensitive than that of the parent for monothiocarbamates (agreement between the hexythiazox parent empirical data and QSAR data was extremely good for this class); therefore, for aquatic invertebrates, chronic toxicity endpoints of transformation products can be presumed

to be higher than the EECs

. Chronic risk to fish cannot be precluded for hexythiazox transformation products.Page 49 of 64 Neither listed nor non

- listed LOCs for aquatic vascular plants were exceeded by the registered hexythiazox uses and the likelihood of adverse effects to vascular aquatic plants is considered

low. For aquatic nonvascular plants, RQs did not exceed the LOC for non

- listed species, and there are no listed aquatic nonvascular plants at this time

.

Considering that aquatic EECs are calculated using conservative residue assumptions ( i.e

., parent + UER), EECs may overestimate exposure. However, in the ab sence of a study employing an acceptably rigorous extraction method, this conservatism is warranted. It is also possible that the solubility of hexythiazox formulated product in the environment exceeds the solubility of the TGAI; however, many of the ava ilable tests utilized a co

- solvent to achieve concentrations in excess of the solubility limit which suggests that even under those circumstances ( i.e. , more bioavailable hexythiazox technical), the LC 50 was still nondefinitive.

Reduction of EEC by reduci ng spray drift, through buffer distances or limiting to ground application would not significantly reduce EECs. Reduction of the spray drift fraction from 5% to 1% ( i.e. limiting use to ground applications) reduces EECs by only 5%

.

4.2.2 . Risks to Terrestrial Organisms

Based on the results of the screening

- level assessment, the registered uses of hexythiazox result

in n o direct acute or chronic effects to birds and mammals.

In order to gain a better understanding of how the EECs for the maximum hexythiazox application rate relate to the toxicity data currently available for birds, T

- REX was used to calculate RQs using the conservative assumption that the highest value in the avian acute oral study ( i.e., acute LD 50 = 2,510 mg a.i./kg

- bw) and the highest value in the avian sub

- acute dietary study ( i.e., acute LC 50 = 2,023 mg a.i./kg

- diet) represent the avian acute endpoints. The resulting

dose

- based and dietary

- based acute RQ s for all size and dietary classes, based on the upper

bound Kenaga values ranged from <0.01 to < 0.04 , all of which are less than the acute risk to avian listed species LOC of 0.1. In actuality, these RQs would be lower than the estimated

values because no effects were identified at the 2,510 mg a.i./kg

- bw acute oral and 5

, 620 mg a.i./kg

- diet subacute dietary exposure levels. Chronic avian effects were identified at 297 ppm.

Based on the EECs calculated in T

- REX and a NOAEC of 100 ppm, the corresponding RQ is 0.45, which does not result in an exceedance of the chronic LOC of 1. Therefore

, the likelihood

of direct adverse effects to birds (and to terrestrial

- phase amphibian and reptiles for which birds serve as surrogates) from acute, sub

- acute , or chron ic exposure to hexythiazox is expected to be

low.

In order to gain a better understanding of how the EECs for the maximum hexythiazox application rate relate to the toxicity data currently available for mammals, T

- REX was used to calculate RQs using the conservative assumption that the highest value in the mammalian acute oral study ( i.e. , acute LD 50 = 5,000 mg/kg and the highest value in the mammalian 2

- generation reproduction study ( i.e. , NOAEL = 2400 ppm) represent the mammalian acute and chronicPage 50 of 64 endp oints. The resulting dose

- based acute RQs for all size and dietary classes, based on the

upper

- bound Kenaga values were all less than 0.01, and are well below the acute risk to mammalian listed species LOC of 0.1. The resulting chronic dietary

- and dose

- based RQs for all size and dietary classes, based on the upper

- bound Kenaga values ranged from <0.02 to < 0.16

and are all less than the chronic risk to mammals LOC of 1. In actuality, these RQs would be

lower than the estimated values because no effects w ere ide ntified at the 5,000 mg a.i./kg bw

acute oral and 2400 mg/kg diet dietary levels. Therefore

, direct risk to mammals from acute and chronic exposure to hexythiazox is expected to be low.

Only non

- definitive acute contact toxicity data is available for terrestrial arthropods; however, given that hexythiazox’s mode of action affects the eggs and juvenile lifestages of mites and that

chronic effects were observed in both the freshwater and estuarine/marine aquatic invertebrate life cycle tests, it is plausible that terrestrial invertebrates are at risk from applications of hexythiazox, potentially from either acute or chronic exposures. Hazard to terrestrial invertebrates, particularly sensitive life stages ( i.e. , egg, larvae, and juvenile; consistent with the susceptible life stages of target arthropods that hexythiazox is efficacious against) may not be

evident from a toxicity test design using adult worker honey bees. The threshold at which larval honey bees are sensitive to hexythiazox is uncertain. It is plausible that adult worker bees, which may forage on crops that are treated at bloom if product labels do not restrict such applications, may serve as vectors of exposure, potentially introducing hexy thiazox

- treated pollen into the hive for consumption by larval stages. Therefore, risk to non

- target terrestrial invertebrates is

considered uncertain

.

D irect effects to monocot and dicot plants are uncertain due to a lack of Tier II seedling

emergence data on onions and oilseed rape, which exhibited greater than 2 5% response in Tier I testing; and incomplete Tier I vegetative vigor testing ( i.e. , data submitted for only six species). The degree of uncertainty regarding seedling emergence sensitivity i s limited c onsidering that eight of 10 tested crop species in the Tier I seedling emergence test did not exhibit phytotoxic

respon se in excess of the 25% trigger. Although the potential for effects cannot be precluded,

this is a line of evidence indicatin g a low potential for effects to herbaceous plants. Similarly,

based on the available Tier I vegetative vigor data

— albeit incomplete, there is no indication that hexythiazox causes excessive phytotoxic response when applied at the maximum label rate.

5. Federally Threatened and Endangered (Listed) Species Concerns

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and

anadromous li sted species, and/or the United States Fish and Wildlife Service (USFWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated critical habitat. Each federal agency is required u nder the Act to ensure that any action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the contin ued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably thePage 51 of 64 likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species" (50 C.F.R. § 402.02).

To facilitate compliance with the requirements of the Endangered Species Act (subsection (a)(2)), the Office of Pesticide Programs has established procedures to evaluate whether a proposed reg istration action may directly or indirectly appreciably reduce the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of any listed species (USEPA, 2004). After the Agency’s screening level risk assessment is conducted, if any of the Agency’s listed species’ LOCs are exceeded for either direct or indirect effects, an analysis is conducted to determine if any listed or candidate species

may co

- occur in the area of the proposed pesticide use or areas downstream or downwind that could be contaminated from drift or runoff/erosion. If listed or candidate species may be present in the proposed action area, further biological assessment is undertaken. The extent to which listed spec ies may be at risk is considered, which then determines the need for the development of a more comprehensive consultation package, as required by the Endangered Species Act.

The federal action addressed herein is the proposed re new ed registration of hexyt hiazox on agricultural use sites. I t is expected that its use could occur nationwide.

5.1. Action Area

For listed species assessment purposes, the action area is considered to be the area affected directly or indirectly by hexythiazox use and not merely the immediate area where hexythiazox is applied. At the initial baseline, the risk assessment considers broadly described taxonomic groups and conservatively assumes that listed species within those broad groups are co

- locat ed with the pesticide treatment area. This means that listed terrestrial plants and wildlife are assumed to be located on or adjacent to the treated site and listed aquatic organisms are assumed to be located in a surface water body adjacent to the treate d site. The assessment also assumes that the listed species are located within an assumed area, which has the relatively highest potential exposure to the pesticide, and that exposures are likely to decrease with distance from

the treatment area.

5.2. Taxonomic Groups Potentially at Risk

If the assumptions associated with the baseline action area result in RQs that are below the listed species LOCs, a "no effect" determination conclusion is made wi t h respect to listed species in that taxa, and no further refinement of the action area is necessary. Furthermore, RQs below the listed species LOCs for a given taxonomic group indicate no concern for indirect effects on listed species that depend upon the taxonomic group for which the RQ was calculated. However, in situations where the screening assumptions lead to RQs in excess of the listed species LOCs for a given taxonomic group, a potential for a "may affect" conclusion exists and may be associated

w ith direct effects on listed species belonging to that taxonomic group or may extend to indirect effects upon listed species that depend upon that taxonomic group as a resource. In such cases, additional information on the biology of listed species, the l ocations of these species, and the locations of use sites are considered to determine the extent to which screening assumptionsPage 52 of 64 regarding an action area apply to a particular listed organism. These subsequent refinement steps

will consider how this inform ation would impact the action area for a particular listed organism and potentially include areas of exposure that are downwind and downstream of the pesticide use

site.

Assessment endpoints, exposure pathways, and the conceptual models addressing hexythi azox uses, and the associated exposure and effects analyses conducted for the hexythiazox baseline

risk assessment are in Sections 2 to 3

. The assessment endpoints used in the baseline risk assessment include those defined operationally as reduced survival and reproductive impairment for both aquatic and terrestrial animal species and survival, reproduction, and growth of aquatic

and terres trial plant species from both direct acute and chronic exposures. These assessment endpoints are intended to address the standard set forth in the Endangered Species Act requiring federal agencies to ensure that any action they authorize does not apprecia bly reduce the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species. Risk estimates (RQs) which, integrating exposure and effects, are calculated for broad based taxonomic groups in the screening

- level risk assessment presented in Section 4.

Both acute endangered species and chronic risk LOCs are considered in the baseline risk assessment to identify direct and indirect effects to taxa of listed species. This se ction identifies direct effect concerns, by taxa that are triggered by exceeding endangered LOCs in the baseline risk assessment, with an evaluation of the potential probability of individual effects for exposures that may occur at the established endanger ed species LOC. Data on exposure and effects collected under field and laboratory conditions are evaluated to make determinations on the predictive utility of the direct effect screening assessment findings to listed species. Potential for

direct effects to listed taxa are described in Table 5.1

.Page 53 of 64 Table 5.1. Potential Effects to Federally Listed Taxa Associated with Direct Effects from

the Registered Uses of H exythiazox

. Listed Plant Taxon Potential Direct Effects

Terrestrial and semi

- aquatic plants

– monocots and dicots Uncertain 1

Aquatic nonvascular plants No Aquatic vascular plants No

Listed Animal Taxon Potential Direct Effects

Acute Chronic

Terrestrial invertebrates Uncertain 2 Uncertain 2

Mammals No 3 No 3

Birds No 3 No 3

Reptiles No 3 No 3

A mphibians No 5 Uncertain 4

Freshwater fish No 5 Uncertain 4

Freshwater invertebrates No 5 Uncertain 6

Mollus k s Uncertain 7 ND

E stuarine /marine fish No 5 Uncertain 4

E stuarine /marine invertebrates No 5 Uncertain 6

ND = Not determined

1 Tier I terrestrial plant testing is incomplete; tier II seedling emergence data is not available for two species that demonst rated effects greater than 25% in tier I testing. Only one tier I vegetative vigor study used TEP for testing (all ot her available tier I vegetative vigor and seedling emergence studies used TGAI); this study only tested response of six species.

2 Although no effects were seen in the acute contact toxicity tests with honey bees, the limit dose (200 μg a.i./bee) was not h igh enough to preclude risk at the listed species LOC (0.4) , based on the tall grass EECs (

~ 20,000 ppb) for registered hexythiazox uses. Further, given that hexythiazox affects eggs and larval life stages of the intended pest arthropods , EFED cannot preclude effects to this taxon.

3 Risk of direct effects from acute and chronic exposure of avian (including reptilian surrogates) and mammalian species to for mulated hexythiazox is expected to be below the LOC.

4 No chronic fish toxicity studies have be en submitted. Fish are surrogates for aquatic phase amphibians.

5 Solubility issues confound the results of acute toxicity testing; no definitive LC/EC 50 values were determined. The acute toxicity of hexythiazox appears to be limited by its solubility.

6 No chronic sediment toxicity studies have been submitted. Hexythiazox’s MOA in conjunction with effects to reproduction obse rved from chronic pelagic invertebrate testing raise chronic risk concerns for sediment dwelling aquatic invertebrates.

7 No acute bivalve studies have been submittedPage 54 of 64 6 . Literature Cited

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of the

EPA food

- chain (Kenaga) nomogram , an instrument for estimating pesticide residues on plants. Environ. Tox. Chem. 13:1383

- 1391.

Hoerger, F. and E. E. Kenaga. 1972. Pesticide Residues on Plants: Correlation of Representative Data as a Basis for Estimation of their Magnitude in the Environment. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Th ieme Publ., Stuttgart, West Germany, pp. 9

- 28.

Mayer, D.F. and J.D. Lunden. 1986. Toxicity of Fungicides and an Acaricide to Honey Bees Apis

- Mellifera Hymenoptera and Their Effects on Bee Foraging Behavior and Pollen Viability on Blooming Apples and Pea rs. Environ Entomol 15 (5): 1047

- 1049.

United States E nvironmental P rotection A gency . 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and Development, Washington, D.C. EPA/630/R

- 95/002F. April 1998. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

US EPA

, 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, Pestic ides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004.

US EPA, 2007. Problem Formulation for Hexythiazox in Hexythiazox Summary Document: Registration Review. Office of Pesticide Programs, January, 2007.

US EPA, 2009. Input Parameter Guidance. Version 2.1. Environmental Fate and Effects

Division. October 22, 2009 http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

US EPA, 2009. Section 3 Label Amendment Request for the Use of Hexythiazox on Potatoes

in the Pacific Northwest. Environmental Fate and Effects Division. Office of Pesticide Progr ams, October 6, 2009.

US EPA. 2010. Incremental Ecological Risk Assessment for New Uses on Turf and Various

Residential Plants. Environmental Fate and Effects Division. Office of Pesticide Programs. May 13, 2010. D334885.

USEPA, 2010 a

. Hexythiazox: Drinking Water Assessment for New Use on Greenhouse Tomatoes. Environmental Fate and Effects Division. Office of Pesticide Programs. December 1, 2010. D383745.Page 55 of 64 US EPA. 2011. Incremental Ecological Risk Assessment for New Uses on Sweet Corn, Dry Beans, Succulent Beans, and Greenhouse Tomatoes. Environmental Fate and Effects Division. Office of Pesticide Programs. February 10, 2011. D364594, 384771, and

382916.

USEPA 2012. Ecological Structure Activity Relationships (ECOSAR) v ersion 1.11. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

U.S. EPA. 2012 a . Incremental Ecological Risk Assessment for New Uses on Alfalfa, Timothy, Eggplant, and Peppers. Environ mental Fate and Effects Division. Office of Pesticide Programs. November 8, 2012. D396529, 401798, 402051 and 404478.

USEPA. 2013. Pesticides: Science and Policy. Terrestrial Models, T

- REX Version 1.5/1. http://www.epa.gov/oppefed1/models/terrestrial/

USEPA. 2013a. Pesticides: Science and Policy. Terrestrial Models, TerrPlant Version 1.2.2. http://www.epa.gov/oppefed1/mode ls/terrestrial/

US EPA. 2013 b . Incremental Ecological Risk Assessment for New Use on Sorghum.

Environmental Fate and Effects Division. Office of Pesticide Programs. April 2 , 2013

. D 404023.

Utah State University Cooperative Extension. Web Spinning Spider Mites. http://utahpests.usu.edu/ipm/htm/fruits/fruit

- insect

- disease/spider

- mites

Willis G.H. and L.L. McDowell (1987) Pesticide persistence on foliage. Rev Environ Contam

Tox : 100:23

- 62.Page 56 of 64 Appendix 1

– PRZM/EXAMS output from scenario with highest EECs

stored as MScorn.out Chemical: HexythiazoxTTR

PRZM environment: MScornSTD.txt modified Tueday, 29 May 2007 at 13:57:40 EXAMS environment: pond298.exv modified Tueday, 26 August 2008 at 06:14:08

Metfile: w03940.dvf modified Tueday , 26 August 2008 at 06:14:14 Water segment concentrations (ppb)

Year Peak 96 hr 21 Day 60 Day 90 Day Yearly

1961 0.6562 0.5535 0.3453 0.3026 0.2918 0.1979

1962 2.383 2.093 1.336 0.9386 0.8495 0.5991

1963 1.165 1.09 0.9485 0.8638 0.8507 0.7764

1964 2.297 2 .031 1.678 1.381 1.302 1.093

1965 1.633 1.549 1.341 1.22 1.191 1.154

1966 2.107 1.943 1.729 1.615 1.552 1.366

1967 2.598 2.399 2.029 1.836 1.775 1.583

1968 2.318 2.242 2.043 1.91 1.864 1.71

1969 3.513 3.195 2.631 2.247 2.146 1.89

1970 2.404 2.312 2.099 2.056 2.008 1.904

1971 3.339 3.08 2.686 2.444 2.347 2.093

1972 2.832 2.692 2.473 2.312 2.261 2.114

1973 4.222 3.9 3.104 2.701 2.587 2.282

1974 4.356 3.97 3.236 2.818 2.723 2.445

1975 3.274 3.125 2.94 2.733 2.684 2.524

1976 3.337 3.19 2.961 2.791 2.732 2.56 8

1977 3.331 3.213 2.931 2.739 2.675 2.534

1978 3.138 3.058 2.903 2.777 2.708 2.52

1979 5.741 5.211 4.058 3.439 3.285 2.885

1980 5.947 5.549 4.493 3.833 3.653 3.187

1981 3.885 3.776 3.495 3.305 3.238 3.097

1982 4.521 4.243 3.723 3.388 3.326 3.118

1983 5.44 4 5.012 4.127 3.789 3.664 3.305

1984 3.922 3.787 3.519 3.416 3.357 3.205

1985 3.506 3.404 3.222 3.095 3.089 2.966

1986 3.61 3.465 3.25 3.05 2.995 2.848

1987 3.267 3.167 2.996 2.906 2.888 2.75

1988 3.45 3.3 2.992 2.842 2.773 2.633

1989 3.853 3.635 3.225 2.9 9 2.909 2.682

1990 3.352 3.227 2.987 2.9 2.841 2.669

Sorted results

Prob. Peak 96 hr 21 Day 60 Day 90 Day Yearly

0.032258064516129 5.947 5.549 4.493 3.833 3.664 3.305

0.0645161290322581 5.741 5.211 4.127 3.789 3.653 3.205

0.0967741935483871 5.444 5.012 4.058 3.439 3.357 3.187Page 57 of 64 0.129032258064516 4.521 4.243 3.723 3.416 3.326 3.118

0.161290322580645 4.356 3.97 3.519 3.388 3.285 3.097

0.193548387096774 4.222 3.9 3.495 3.305 3.238 2.966

0.225806451612903 3.922 3.787 3.25 3.095 3.089 2.885

0.258064516129032 3. 885 3.776 3.236 3.05 2.995 2.848

0.290322580645161 3.853 3.635 3.225 2.99 2.909 2.75

0.32258064516129 3.61 3.465 3.222 2.906 2.888 2.682

0.354838709677419 3.513 3.404 3.104 2.9 2.841 2.669

0.387096774193548 3.506 3.3 2.996 2.842 2.773 2.633

0.4193548387096 77 3.45 3.227 2.992 2.818 2.732 2.568

0.451612903225806 3.352 3.213 2.987 2.791 2.723 2.534

0.483870967741936 3.339 3.195 2.961 2.777 2.708 2.524

0.516129032258065 3.337 3.19 2.94 2.739 2.684 2.52

0.548387096774194 3.331 3.167 2.931 2.733 2.675 2.445

0.580 645161290323 3.274 3.125 2.903 2.701 2.587 2.282

0.612903225806452 3.267 3.08 2.686 2.444 2.347 2.114

0.645161290322581 3.138 3.058 2.631 2.312 2.261 2.093

0.67741935483871 2.832 2.692 2.473 2.247 2.146 1.904

0.709677419354839 2.598 2.399 2.099 2.056 2.008 1.89

0.741935483870968 2.404 2.312 2.043 1.91 1.864 1.71

0.774193548387097 2.383 2.242 2.029 1.836 1.775 1.583

0.806451612903226 2.318 2.093 1.729 1.615 1.552 1.366

0.838709677419355 2.297 2.031 1.678 1.381 1.302 1.154

0.870967741935484 2.107 1.943 1.341 1.22 1.191 1.093

0.903225806451613 1.633 1.549 1.336 0.9386 0.8507 0.7764

0.935483870967742 1.165 1.09 0.9485 0.8638 0.8495 0.5991

0.967741935483871 0.6562 0.5535 0.3453 0.3026 0.2918 0.1979

0.1 5.3517 4.9351 4.0245 3.4367 3.3539 3.1801 Average of yearly averages: 2.22328

Inputs generated by pe5.pl

- Novemeber 2006

Data used for this run: Output File: MScorn

Metfile: w03940.dvf

PRZM scenario: MScornSTD.txt

EXAMS environment file: pond298.exv

Chemical Name: HexythiazoxTTR Description Variable Name Value Units Comments Molecular weight mwt 352.5 g/mol Henry's Law Const. henry 3.87E

- 8 atm

- m^3/mol Vapor Pressure vapr 1E

- 8 torr Solubility sol 0.12 mg/L

Kd Kd mg/LPage 58 of 64 Koc Koc 6188 mg/L Photolysis half

- life kdp 17 days Half

- life Aerobic Aquatic Metabolism kb acw 145 days Halfife Anaerobic Aquatic Metabolism kbacs 0 days Halfife

Aerobic Soil Metabolism asm 114 days Halfife Hydrolysis: pH 7 0 days Half

- life

Method: CAM 2 integer See PRZM manual Incorporation Depth: DEPI 0 cm Application Rate: TAPP 0.21 kg/ha App lication Efficiency: APPEFF 0.95 fraction Spray Drift DRFT 0.05 fraction of application rate applied to pond Application Date Date 10

- 4 dd/mm or dd/mmm or dd

- mm or dd

- mmm Record 17: FILTRA

IPSCND 1

UPTKF

Record 18: PLVKRT

PLDKRT

FEXTRC 0.5 Flag for Index Res. Run IR EPA Pond Flag for runoff calc. RUNOFF none none, monthly or total(average of entire run)Page 59 of 64 Appendix 2. Hexythiazox Aquatic Ecological Effects Summaries

Much of the original toxicological data cited in previous ecological risk assessmen ts for hexythiazox was deemed acceptable. However, a more recent review of this data found that several of the studies had hexythiazox concentrations that were above solubility (reported to range from 105 in slow flowing distilled water to 126 ppb in fast flowing distilled water) and water samples were not centrifuged or alternatively filtered prior to processing and analysis. Solubility under actual test conditions is unknown. Additionally, dissolved hexythiazox

concentrations were not stable and in sev eral acute studies, final concentrations had declined to

10%

- 70% of initial concentrations. These issues were not captured in the initial reviews. Therefore, EFED downgraded several of these studies based on the rationale provided below.

Acute Fish

MR ID 00260839 . This static test design rainbow trout ( Oncorhynchus mykiss ) study was initially considered to meet the 850.1075 guideline requirement. However, hexythiazox concentrations were above solubility at all treatment levels and water samples were no t centrifuged or alternatively filtered prior to processing and analysis. Although a DMF co

- solvent was used, surface films and solution cloudiness were recorded at all test levels. Final hexythiazox

concentrations had declined to 10%

- 59% of initial meas ured concentrations, and there were overlapping concentrations between most treatment levels. No mortalities occurred in the study, but sublethal effects (lying on bottom, irregular opercular movement ) occurred in the four highest treatment levels. Therefo re, this study has been downgraded from “acceptable” to “supplemental”; and the non

definitive LC 50 value is assumed to be greater than hexythiazox’s solubility in water (120 μg a.i./L ; MRID 44006301 ). Submittal of an acute freshwater study

that meets the requirements specified in OCSPP 850.1075 and 850.1000 for compounds with low water solubility would reduce the uncertainties associated with solubility issues and overlapping treatment concentrations observed in the available rainbow trout study.

MRID 0 0260839 . This static test design bluegill sunfish ( Lepomis macrochirus ) study was initially classified as acceptable. However, hexythiazox concentrations were above solubility at all treatment levels and water samples were not centrifuged or alternatively filtered prior to processing and analysis. Although a

DMF co

- solvent was used, surface films and solution cloudiness were recorded at all higher treatment concentrations. Final hexythiazox concentrations had

declined to 16%

- 80% of initial m easured concentrations, and there were overlapping concentrations at the four highest treatment levels. Sublethal effects were not recorded, but mortalities occurred at all test concentrations. Therefore, this study has been downgraded from “acceptable” to “supplemental”, and the

non

- definitive LC 50 is assumed to be greater than hexythiazox’s solubility in water (120 μg a.i./L ; MRID 44006301 ). However, since 20% mortality (compared to 0% mortality in the controls) occurred at the lowest test concentratio n which wasPage 60 of 64 still above solubility, this approach may under represent the actual toxicity of hexythiazox to warmwater fish. Submittal of an acute freshwater study that meets the requirements specified in OCSPP 850.1075 and 850.1000 for compounds with

low water solubility would reduce the uncertainties associated with solubility issues and overlapping treatment concentrations observed in the available bluegill sunfish study.

MRID 47315801 . This static test with sheepshead minnow ( Cyprinodon variegatus ) wa s classified as supplemental because final measured concentrations were only 11

- 24% of the initial concentrations. No mortality was observed in the highest nominal treatment group (1.0 mg a.i./L), although one fish in this treatment exhibited partial loss of equilibrium at 96 hours. The supplemental study classification was not changed.

Acute Freshwater Invertebrates

MRID 00072940 . This study on Daphnia carinata was initially considered to be acceptable. Immobilization was observed at all treatment levels above the lowest treatment dose. However, no raw data was submitted indicating analytical measurements of test substance concentrations, observations of precipitates or indication of centrifugation/filtration of samples prior to processing, or

conc entration of solvent (Tween) used. Therefore, this study has been downgraded to invalid. This study may be upgraded if the raw data is submitted. Submittal of an acute freshwater study that meets the requirements specified in

OCSPP 850.1075 and 850.1000 for compounds with low water solubility would reduce the uncertainties associated with solubility issues observed in the available daphnid study.

MRID 48743406. This recently submitted study tested response of Daphnia

magna to five concentrations of hex ythiazox transformation product PT

- 1

- 2. The

48

- hr EC 50 was determined to be to be 17.6 mg a.i./L. This study is classified as acceptable.

MRID 48743407

. This recently submitted study tested response of Daphnia

magna to hexythiaz ox transformation product PT

- 1

- 3

. The PT

- 1

- 3 EC 50 was determined to be greater than the limit of solubility (7.9 mg/L). This study is

classified as supplemental.

MRID 48743408

. This recently submitted study tested response of Daphnia

magna to hexythiaz ox transformation product PT

- 1

- 9

. The PT

- 1

- 9 EC 50 was determined to be greater than the limit of solubility (7.9 mg/L). This study is

classified as supplemental.

Chronic Freshwater InvertebratesPage 61 of 64 MRID 00261731. This study on Daphnia magna was initially considered to be supplemental due to a lack of raw data. However, control samples were contaminated with hexythiazox, initial analytical measurements of concentrations were not conducted on three treatment levels and analytical measurements of

concentrations were also mi ssing at other time series. Therefore, this study has been downgraded from “supplemental” to “invalid.”

MRID 43944701 . This study on D. magna was initially considered to be supplemental due to a higher flow rate (20 vol/24 hours) and lower DO levels (40

- 60% in Day 21 samples) in the solvent control and all treatment levels than recommended by the guideline. Dissolved oxygen levels were only below 60% in the Day 21 samples and the study author’s attempted to raise this by increasing the cycle rate, clean ing the test chambers, and aeration. Despite these low DO concentrations, neither mortality, growth, nor reproductive parameters were affected in the solvent control (DO levels did not drop in the negative control) in comparison to the negative control. Therefore, the low DO concentrations do not appear to have had a significant effect on the study endpoints. Final hexythiazox

concentrations were maintained at > 70% of initial concentrations with the exception of the lowest treatment level. Since effec ts were not seen at this level, the study is considered adequate to characterize the chronic toxicity of hexythiazox to freshwater invertebrates and has furthermore been upgraded to acceptable. The chronic endpoint of 6.1 μg a.i./L, based on survival, wil l be used in this risk assessment. Cumulative mortality of 17% was recorded at the 6.1 μg a.i./L treatment level (cumulative mortality in the negative control was 15%). Additionally, reproductive effects were seen as the number of offspring per

female wa s significantly reduced compared to the negative control at concentrations as low as 54 ppb, resulting in an inhibi tion of 46 % at this LOAEC. The NOAEC for reproductive effects seen in this study was 27.7 ppb.

MRID 48910705. A 21

- day larval development test with freshwater benthic

invertebrate Chironomus riparius was recently submitted. First instar larvae (less than three days old) in a water

- sediment system were exposed to s even test
concentrations ranging from 0.1

- 6.4 mg/ L. Both a negative and dispe rsant (solvent) control were used in the test design. Neither emergence nor development rate were significantly reduced in any of the hexythiazox treatments compared to the negative control. This study is classified as supplemental.

Acute & Chronic Est uarine/Marine Invertebrates

MRID 47450601 . This acute flow

- through study on mysids is considered to be acceptable. No effects were seen at any treatment level. The highest treatment level of 110 ppb (measured concentration) was near the limit of solubi lity; however, filters were used to prevent precipitate from entering the test chambers

and final test concentrations were similar to initial test concentrations. The LC 50 is non

- definitive; >110 μg a.i./L.Page 62 of 64 MRID 48114001 . This chronic flow

- through mysi d study is classified as acceptable. Survival, growth, and reproductive endpoints were all affected. Final

concentrations were similar to initial concentrations. The chronic NOAEC of 8.89 ppb, based on day 14 length of F 0 and F 1 males, will be used in this risk assessment. Additionally, reproductive effects were seen as the number of offspring per female was significantly reduced compared to the negative control at concentrations as low as 34 ppb, resulting in an inhibition of 6 7% at this LOAEC. The NOAEC for reproductive effects seen in this study was 17.2 ppb.

No data is availab le for estuarine/marine bivalves . EFED will characterize risk to these species by using the estuarine/marine mysid acute and chronic toxicity data

as a surrogate for the mussel data. Submittal of acute and chronic estuarine/marine bivalve studies that meet the requirements specified in OCSPP 850.1055 would reduce the uncertainties in this assessment associated with using mysid data as a surrogate fo r estuarine/marine bivalves. Data is also not available

for estuarine/marine benthic invertebrates. Submittal of whole sediment chronic toxicity tests with estuarine/marine benthic invertebrates that meet the requirements specified in “USEPA 2001 Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- associated Contaminants with the Amphipod Leptocheirus plumulosus EPA 600/R

- 01/020 ( OCSPP 850.1780, in

prep. )” would reduce the uncertainties in this assessment associated with a lack

of t his data.

Aquatic Plants

MRID 47450602 . This static renewal study on the freshwater vascular plant Lemna gibba was initially considered to be acceptable. However, 3

- day renewal

concentrations declined to below 70% of initial concentrations. Therefore , this study was downgraded from “acceptable” to “supplemental”. Given that no signs of toxicity were observed at the highest treatment level, which was above the level of solubility, the non

- definitive EC 50 value is considered to be the limit of

solubili ty.

MRID 48910706. This recently submitted study evaluated response of freshwater nonvascular green algae Desmodesmus subspicatus to seven concentrations of hexythiazox. The EC 50 was determined to be >120 μg/L, and the cell density

NOAEC was statistically determined to be 25 μg/L ( nominal concentration )

. The study is classified as supplemental.

MRID 48910703. This recently submitted study evaluated response of freshwater nonvascular green algae Ankistrodesmus bibraianus

. All test concentrations were above the limit of hexythiazox’s solubility and no solvent was used; therefore, this study is classified as invalid.Page 63 of 64 Appendix 3. ECOSAR runs to support toxic equivalency approach

Freshwater Fish Acute

Chemical Endpoint (m g/ L) Thiazoldinones (mg/L) Monothiocarbamates (m g/L) Carbonylureas ( m g/L) Neutral (m g/L)

P arent > 0.12 0.326 0.423 0.44 0.179

PT

- 1

- 2 1.46 4.129 22.88 11.317 39.378

PT

- 1

- 3 no data 3.14 16.517 n/a 27.033

PT

- 1

- 4 no data 1.648 4.84 3.314 4.512

PT

- 1

- 5 no data 2.77 10.666 6.357 12.921

PT

- 1

- 8 no data 1.648 4.84 3.314 4.512

PT

- 1

- 9 1.22 2.77 10.666 6.357 12.921

E/M Fish Acute

Chemical Endpoint (m g/L) Thiazoldinones (m g/L) Monothiocarbamates (mg/L) Carbonylureas (mg/L) Neutral (m g/L)

P arent >0.12 n/a 0.211 0.385 n/a

PT

- 1

- 2 no data n/a 4.553 9.893 n/a

PT

- 1

- 3 no data n/a 3.397 n/a n/a

PT

- 1

- 4 no data n/a 1.441 2.898 n/a

PT

- 1

- 5 no data n/a 2.673 5.558 n/a

PT

- 1

- 8 no data n/a 1.441 2.898 n/a

PT

- 1

- 9 no data n/a 2.673 5.558 n/a

Mysid Acute

Chemical Endpoint (m g/L) Thiazoldinones (m g/L) Monothiocarbamates (mg/L) Carbonylureas ( m g/L) Neutral (m g/L)

P arent > 0.11 n/a 0.059 0.000223 n/a

PT

- 1

- 2 no data n/a 3.721 0.824 n/a

PT

- 1

- 3 no data n/a 2.671 n/a n/a

PT

- 1

- 4 no data n/a 0.736 0.027 n/a

PT

- 1

- 5 no data n/a 1.669 0.133 n/a

PT

- 1

- 8 no data n/a 0.736 0.027 n/a

PT

- 1

- 9 no data n/a 1.669 0.133 n/aPage 64 of 64 Algae Acute

Chemical Endpoint (m g/L) Thiazoldinones (m g/L) Monothiocarbamates (m g/L) Carbonylureas ( m g/L) Neutral (mg/L)

P arent > 0.12 n/a 0.052 0.026 0.413

PT

- 1

- 2 8.67 n/a 0.665 0.02 24.771

PT

- 1

- 3 no data n/a 0.506 n/a 17.816

PT

- 1

- 4 no data n/a 0.265 0.028 5.007

PT

- 1

- 5 no data n/a 0.445 0.028 11.251

PT

- 1

- 8 no data n/a 0.265 0.028 5.007

PT

- 1

- 9 11.9 n/a 0.445 0.028 11.251