-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 

exposure 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 terrestrial 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 hexythiazox. 
Page 3 of 64

Table 1. Risk Resulting from Hexythiazox Exposure Presented by Taxon

Use Pattern Category1 Aquatic 

Invertebrates

Fish (surrogate 

for aquatic-phase 

amphibians)

Birds, 

(surrogate for 

terrestrialphase 

amphibians 

and reptiles)

Mammals Plants Terrestrial 

Invertebrates

Field Corn, Sweet Corn, 

Dry and Succulent Beans, 

Pepper, Eggplant, Alfalfa, 

Timothy, Ornamental 

lawns and turf, Nonresidential 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, 

Cotton

Acute risk:

Not expected; 

acute toxicity is 

limited by 

solubility

Chronic risk: 

Not expected 

for pelagic 

invertebrates; 

uncertain for 

sedimentdwelling 

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 nonlisted plants 

is uncertain

Aquatic:

Not expected

Non-listed and 

Listed:

Uncertain; 

likelihood of 

risk

1 Risk conclusions apply to all registered hexythiazox use patterns
Page 4 of 64

Basic 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 

sensitivity 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 uncertainty; 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 extraction 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 

to 67%. 

Quantitative Structure Activity Relationship (QSAR) modeling 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, 

specifically 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

(4RS,5RS)-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

June 13, 2013
Page 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 ....................................................................................................................................54
Page 7 of 64

1. Executive Summary

EFED has completed the Registration Review 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: 128849) and its end-use products. Hexythiazox is 

an 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 currently 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, 2013b; D404023), the Section 3 new use assessment for 

alfalfa, timothy, eggplant, and peppers (USEPA, 2012a; D396529+), the Section 3 new use 

assessment for field corn, sweet corn, dry beans, succulent beans and greenhouse tomatoes 

(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 

Northwest (USEPA, 2009; D338695), and an initial Problem Formulation for the for 

Registration Review (Document Number: EPA-HQ-OPP-2006-0114). The two most recent new 

use assessments (D404023 and D396529+) have been conducted with the total toxic residues 

(TTR) approach; preceding assessments additionally considered 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 KOC of 6,188 mL/g o.c. 

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

extractions and high unextracted 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 with 

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 20oC and Henry’s Law constant=. 3.87 x 10-8 m3 atm g/mol at 20oC)). Although the 

compound is considered slightly mobile, it may access water through runoff of sediment-bound 

residues (erosion).

Hexythiazox 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 freshwater 
Page 8 of 64

invertebrates 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. Hexythiazox is practically nontoxic to birds, mammals, and beneficial insects (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 response 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 exposure is considered low for avian species. Based on the available plant toxicity 

data, hexythiazox exhibited low toxicity 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%.

Potential effects to federally-listed endangered and threatened species (listed species) based on 

LOC exceedances require an in-depth listed species evaluation determining the potential cooccurrence of listed species and use patterns of hexythiazox. Identified 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 Hexythiazox.

Listed Plant Taxon Potential Direct Effects

Terrestrial and semi-aquatic 

plants – monocots and dicots Uncertain1

Aquatic nonvascular plants No

Aquatic vascular plants No

Listed Animal Taxon Potential Direct Effects

Acute Chronic

Terrestrial invertebrates Uncertain2 Uncertain2

Mammals No3 No3

Birds No3 No3

Reptiles No3 No3

Amphibians No5 Uncertain4

Freshwater fish No5 Uncertain4

Freshwater invertebrates No5 Uncertain6

Mollusks Uncertain7 ND

Estuarine/marine fish No5 Uncertain4

Estuarine/marine invertebrates No5 Uncertain6

ND = Not determined 1 Tier I terrestrial plant testing is incomplete; tier II seedling emergence data is not available for two species that demonstrated effects greater than 

25% in tier I testing. Only one tier I vegetative vigor study used TEP for testing (all other 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 high 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 formulated 

hexythiazox is expected to be below the LOC. 

4 No chronic fish toxicity studies have been submitted. Fish are surrogates for aquatic phase amphibians.
Page 9 of 64

5 Solubility issues confound the results of acute toxicity testing; no definitive LC/EC50 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 observed 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 and 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 non-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 current 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 refinements include more detailed 1) species-specific ecological 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 habitats of concern. Examples of such 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). Information 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 Pesticide Registration Information System (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 habitat, diet, life history 

variables, and temporal and spatial 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 derive 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 listed 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, field 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 

available) and national land-cover datasets that indicate potential use sites (e.g., national land 
Page 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 outlining 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, and 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 employed 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 into 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 comment 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 determinations 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 site (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 estimated 
Page 11 of 64

environmental 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 Quantitative Structural Activity 

Relationship (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 represent the additional risk from 

hexythiazox degradates. Available ecological 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 plants. 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 Registration 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 uses of 

hexythiazox (USEPA, 1998). 

2.1. Nature of Regulatory Action

Under the Federal Insecticide, Fungicide, 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 pesticide 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., Registration Review1. 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 unreasonable 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 changes 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 

Endangered 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, 2013b; D404023), the Section 3 incremental new use 

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

3 incremental new use assessment for field corn, sweet corn, dry beans, succulent beans and 

greenhouse tomatoes (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 

crops, 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 ovicide, 

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 hexythiazox 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 Plants and Nonbearing 

Fruit Trees; Vines Growing in 

Nurseries; Greenhouses, 

Shadehouses and Christmas Tree 

1 Ground and 

Air
Page 13 of 64

Plantations; Established Ornamental 

Landscape Plantings; Ornamental 

Lawns and Turf; Non-residential 

Turf; Pome Fruit; Stone Fruit; Nut 

Trees; Caneberries; 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

10163-

303

Emulsifiable

Concentrate

48 Caneberries; 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 

Plants and Nonbearing Fruit Trees;

Vines Growing in Nurseries,

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 usage assessment presents usage data on an annual basis and is derived from 
Page 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 walnuts being the dominant use patterns. Though these data are 

indicative of a small use pattern, new uses on 10 crops and various non-agriculture uses have 

been approved since 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 uses of hexythiazox assumes 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 labeled 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

STRESSOR Foliage applied Hexythiazox and its resulting degradates

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 Environments

*Dotted lines indicate that, although this exposure route/media was considered, its contribution to the fate and transport of hexythiazox is expected to be negligible
Page 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 of 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 of 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 organisms.

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 endpoint 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 represent 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 differential 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 beyond 
Page 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 uses 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 exposure 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 Degradation Kinetics 

in Environmental Media (Bohaty et al., 2012; NAFTA, 2012). These updated results will be 

used in estimating model inputs for estimating aquatic exposure. 

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 (EECs) 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 ECOTOXicity (ECOTOX)2 database, 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 Endangered Species Act (ESA), the 

Agency evaluates 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 process 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 Disruptor 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, 

developmental 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 required 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 ingredients) 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 

determinations. 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 found 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 any 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 February 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 screened 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 procedures, 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 stable 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 improved 

extractions and lower unextracted residues in a field lysimeter 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 field 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 

aerobic aquatic systems with half lives ranging 76 to 110 days. Hexythiazox is stable to 

hydrolysis though it photolyzes in water with a half life of 17 days. Parent hexythiazox is 

slightly mobile with a KOC of 6,188 mL/g o.c. 

Parent hexythiazox is initially 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 KOC 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 and 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 through 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 radioactivity (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: (4RS,5RS)-5-(4-

chlorophenyl)-N-cyclohexyl-4-

methyl-2-oxo-1,3-thiazolidine-3-

carboxamide

CAS: (4R,5R)-rel-5-(4-

chlorophenyl)-N-cyclohexyl-4-

methyl-2-oxo-3-

thiazolidinecarboxamide

CAS No.: 78587-05-0

Formula: C17H21ClN2O2S

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

KOC: 406 mL/g o.c. (MRID 

48743402)

Hydrolysis 

22°C 00141516 ND ND
Page 21 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-methylthiazolidin-2-one

Formula: C10H10ClNOS

MW: 227.71 g/mol

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

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

KOC: 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

KOC: 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: CO2

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 1x 10-8 mm Hg 44006301 Supplemental

KOW 337 143533 Supplemental

Direct Aqueous 

Photolysis 

t1/2 = 26.7 days with 

natural light (TTR)

PC-1-2

PT-Cy-O; PT-CyOH; PT-1-2; PT-1-

3; PC-1-1; 

unidentified. 

00146539 Supplemental

Aerobic Soil 

Metabolism 

t1/2 = 70 days (sandy 

loam at 25oC) and 49 days 

(sandy clay loam) for 

parent and 

UER ; 

t1/2 = 21 days (sandy 

loam at 25o

C) and 17 days 

(sandy clay loam) for 

parent only

PT-1-2; PT-Cy-O

PT-1-3; PT-CyOH; 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. t1/2 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.

t1/2 = 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

t1/2 = 110 days (sandy 

loam) and 76 days (sand); 

t1/2 calculations include 

UER.

t1/2 = 43 days (sandy 

loam) and 30 days (sand); 

t1/2 calculations include 

parent only. 

PT-1-2; PT-1-9

PT-1-3; PT-1-4; 

PT-1-8

48910702 Supplemental
Page 25 of 64

Study Value (units) Major Degradates 

Minor Degradates MRID # Study Status and 

Comments

Kd-ads (mL/g);

Koc- ads (mL/g) 

16, 30, 32, and 63-63.3 

mL/g.; 2638, 3218, 5769, 

and13167 mL/goc . 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

t1/2 = 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 has 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 be 

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 pesticide 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 accordance with current input 
Page 26 of 64

parameter guidance (USEPA, 20093

). Application dates were generally set for the crop 

emergence date in the PRZM scenario. This period is selected because hexythiazox is applied to 

foliage to control target pests (e.g., Banks grass mite 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 applications 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/EXAMS 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 m3 atm g/mol N/A Calculated from vapor 

pressure/solubility

Vapor Pressure 1x 10-8 mm Hg 44006301

Solubility in Water 0.12 ppm 44006301

Photolysis in Water 17.0 days (parent only) 00146539; 

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 

00146542; unreviewed interim 

report that does not 

achieve DT50 or 

characterize degradates

Koc

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.htm
Page 27 of 64

Aquatic exposure modeling, using PRZM-EXAMS, was performed to estimate exposures for

registered uses of hexythiazox. The down-the-drain model within the Exposure and Fate 

Assessment Screening Tool (E-FAST4; v2.0) was used to model exposure from the greenhouse 

tomatoes use pattern (USEPA, 2010a; D383745); however, this greenhouse use pattern resulted 

in negligible aquatic exposure relative to the outdoor uses. 

Table 7. Summary of Use Specific Inputs for PRZM/EXAMS Modeling

 4 USEPA. 2013. Council for Regulatory Environmental Modeling. Exposure and Fate Assessment Screening Tool 

(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 Emergence1 1 0.1875

CA Cotton Cotton Emergence 1 0.1563

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 nonflowering plants, 

Ornamental 

shrubs and vines

Used March 1 date1 1 0.1875

CA Rangeland Alfalfa, Timothy Maturity 1 0.1875

CA Strawberry Strawberry Emergence1 1 0.1875

CA Wheat Alfalfa, Timothy Emergence1 1 0.1875

FL Nursery

Non-bearing 

trees, Orchids, 

Christmas Trees, 

Ornamental nonflowering plants, 

Ornamental 

shrubs and vines

Used March 1 date1 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 0.1875
Page 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 nonflowering plants, 

Ornamental 

shrubs and vines

Used March 1 app 

date1 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 nonflowering plants, 

Ornamental 

shrubs and vines

Used March 1 app 

date1 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 0.1563

OR Nursery

Non-bearing 

trees, Orchids, 

Christmas Trees, 

Ornamental nonflowering plants, 

Ornamental 

shrubs and vines

Used March 1 app 

date1 1 0.1875

OR Wheat Alfalfa, Timothy Emergence 1 0.1875

OR Xmas trees Christmas Trees Used March 1 app 

date1 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 0.1875
Page 29 of 64

1 Nursery emergence dates are variable. A March 1 emergence date was selected as 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 Unextracted Residue in Surface Water

TN Nursery

Non-bearing 

trees, Orchids, 

Christmas Trees, 

Ornamental nonflowering plants, 

Ornamental 

shrubs and vines

Used 3-1 app date1 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 1.65
Page 30 of 64

Table 9. Peak EECs for Use Pattern 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, Nonresidential 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 2.47
Page 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 degradate 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 KOC equaling 

6,188 mL/g o.c. and the most mobile degradate KOC 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 KOC with the degradate KOC in a sample 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 degradates 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 Percent Reduction upon Exclusion 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 42

Dry Beans, 

Succulent Beans 50

Hops

45

Sorghum 33 Caneberries 46

Alfalfa, Timothy, 

Ornamental Lawns 

and Turf, Nonresidential Turf 53

Citrus (CA, AZ, 

TX)

56

Grapes 50 Christmas Trees 38

Dates 49 Mint 43

Non-bearing trees, 

Orchids, 

Christmas Trees, 

Ornamental nonflowering 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 water 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%. This 
Page 33 of 64

difference and the uncertainty associated with the data in the environmental fate 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-REX5 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 weight 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 Version 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 is estimated using the TerrPlant6

(version 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 default 

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 SemiAquatic Areas 

(channelized runoff + 

drift)

Drift EEC

Ground spray Aerial 

spray

Ground 

spray

Aerial 

spray

Ground 

spray

Aerial 

spray

0.1875 0.0038 0.0113 0.0206 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 Characterization7

Aquatic toxicity data for animals and plants are summarized in Table 14. For freshwater and 

estuarine/marine fish and invertebrates, the acute toxicity of the compound (in terms of an LC50) 

is limited by its solubility, i.e., 0.12 mg/L, as none of the studies were able to establish a 

definitive LC50. On a chronic exposure basis, hexythiazox resulted 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 at 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 are non-definitive. 

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

concentrations tested. The 14-day EC50 for the vascular aquatic plant duckweed (Lemna gibba)

was >120 μg a.i./L. Data were available for only one non-vascular aquatic plant species, the 

freshwater green algae Desmodesmus subspicatus, with a 96-hr EC50 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. Additionally, 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 

downgraded (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 

LC50/EC50

(μg a.i./L)

48-hr EC50

(μg a.i./L)

Toxicity 

Classification 

(MRID)

NOAEC/

LOAEC

(μg a.i./L)

Endpoints

(MRID)

Rainbow trout

(Oncorhynchus mykiss) > 120 -- Highly Toxic1(00260839) NA --

Bluegill sunfish

(Lepomis macrochirus) > 120 -- Highly Toxic1(00260839) NA --

Waterflea

(Daphnia magna) -- -- No data 6.1/12.7 Survival (43944701)

Sheepshead minnow

(Cyprinodon 

variegatus)

> 120 -- Highly Toxic1

(47315801) NA --

Mysid shrimp

(Americamysis bahia) -- > 1102 Highly Toxic1(47450601) 8.89/17.2

F0 & F1 male 

length

(48114001)

Duckweed

(Lemna gibba) -- 7-day EC50> 120 (47450602) 120/ >120 NA(47450602)

Green algae toxicity 

(Desmodesmus 

subspicatus)

-- 72-hr EC50

> 120 (48910703) 25 NA

(48910706)

1 Although 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. Filters 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 hexythiazox to fish based on the use of 

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

ECOSAR8 v1.11. All 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 invertebrate 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 daphnia). There is good agreement between the experimentally 

derived freshwater aquatic invertebrate 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 transformation 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.htm
Page 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

Chemical Endpoint 

(μg/L)

Thiazoldinones

(μg/L)

Monothiocarbamates

(μg/L)

Carbonylureas

(μg/L)

Neutral

(μg/L)

Parent 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 17 and 18,

respectively. Hexythiazox 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 studies, 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 on food consumption at mean-measured concentrations of 297 mg/kgdiet, resulting in a NOAEC of 100 mg a.i./kg-diet. High coefficients of variation, ranging 

between 42 and 53% for eggs laid per pen, and 62 and 89% for male weight gain, likely limited

the power 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 LD50 >200 μg 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 and 
Page 38 of 64

estuarine/marine invertebrate life cycle tests, there 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 emergence (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; however, 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), 

available data indicate that 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 found that applications of 

hexythiazox at a rate of 0.249 lb a.i./acre decreased 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 that hexythiazox is unlikely to be applied during bloom

(although EFED notes that labels do not prohibit applications during bloom).

Table 17. 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 

(Dosebased)

Mallard duck

(Anas 

platyrhynchos)

Single oral 

dose

>2510 

mg/kg bw 

(LD50)

072940

(acceptable)

1b. Acute 

(Dietarybased)

Northern 

Bobwhite 

(Colinus 

virginianus) & 

Mallard duck

(Anas 

platyrhynchos)

8-Day 

dietary

>5620 

mg/kg diet

(LC50)

072940

(acceptable)

1c. Chronic 

(Dietarybased) 

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

(LD50)

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 > 200μg/bee

072939 

(acceptable)

Table 18. Summary of Tier I Terrestrial Plant Toxicity Data for Hexythiazox

Crop Species EC25 (lbs 

a.i./A)

NOAEC (lbs 

a.i./A)

Most sensitive 

parameter MRID

Seedling Emergence

Monocots

Oat >0.16 0.16 NA 48211801

Ryegrass >0.21 0.21 NA 47433305

Corn >0.16 0.16 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 0.16 NA 48211801

Tomato >0.21 0.21 NA 47433305

Cucumber >0.21 0.21 NA 47433305

Bean >0.16 0.16 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 of this 

review show no reported incidents.
Page 40 of 64

However, because 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 hexythiazox. 

Reporting by states is only voluntary, and individuals discovering incidents may not be informed 

on the procedure of reporting these occurrences. Additionally, much of these databases 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 invertebrates 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 incidents.

4. Risk Characterization

4.1. Risk Estimation

4.1.1. Aquatic Organisms 

The peak EECs 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 EECs represents chronic exposure to aquatic invertebrates and fish, respectively. Acute 

and chronic RQs for freshwater and estuarine/marine animals are summarized in Table 17. RQs 

for aquatic vascular and nonvascular plants are presented in Table 18.

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 17).

No data were available to assess chronic risk to freshwater or estuarine/marine fish; however, a 

QSAR approach was employed which estimated chronic fish endpoints ranging from 3 to 26 

μg/L for carbonyl urea and neutral organic classes, 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, the 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 degradate 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 invertebrates because no effects 
Page 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 17,600 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 chronic 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 19). For hexythiazox 

transformation products, chronic daphnid QSAR 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 19. 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 4.02

NOT TOXIC AT SOLUBILITY LIMIT

NO DATANO DATA

NOT 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 nonflowering plants, 

ornamental shrubs and 

vines

1.82 1.54

0.25 0.17

NC Apple/ Pome fruits: 

apple, 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 0.12
Page 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 nonlisted 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

EC50 > 120 μg a.i./L

NOAEC = 120 μg a.i./L

Nonvascular Aquatic Plant RQs

EC50 > 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. Only non-definitive acute and

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

RQs are presented in Tables 21 and 22. Further discussion of the predicted exposure values 

relative to the levels at which no mortality occurred is provided 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). Only 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 22. In a chronic avian 

reproduction study, significant reduction was determined at the 297 mg/kg-diet treatment level 

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/Uses

Application Rate (lb 

a.i./A) x No. of Apps

RQs for Birds 

(20g small bird consuming short grass)

Acute Dose 

Based1

Acute Dietary 

Based2

Chronic Dietary 

Based3

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, nonresidential 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: apple, 

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). RQs 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 LD50 >2510 mg/kg bw 2

Based on dose-based EEC and Northern bobwhite quail and Mallard duck subacute dietary LC50 >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 Hexythiazox*

Scenario/Uses

Application Rate (lb 

a.i./A) x No. of Apps

RQs for Small Mammals

(small [15g] mammals consuming short grass)

Acute Dose 

Based1

Chronic Dose 

Based2

Chronic Dietary 

Based3

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, nonresidential 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: apple, 

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). RQs 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 LD50 >5000 mg/kg bw 2

Based on chronic dose-based EEC and Norway rat LD50 >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, hexythiazox is classified as ‘practically nontoxic’ to non-target 

terrestrial insects including honey bees (honeybee acute contact LD50 >200 μg ai/bee). If an RQ 

were calculated for terrestrial invertebrates9, conservatively assuming the LD50 to be 200 μg 

ai/bee and 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 online at 

regulations.gov, under docket EPA-HQ-OPP-2012-0543
Page 47 of 64

would be 103. This RQ value exceeds the terrestrial invertebrate LOC (0.4) by more than two 

orders of magnitude.

4.1.2.4. Plants

Since 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 the 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 of hexythiazox range from 0.0113 lb a.i./acre for 

dry areas to 0.0281 lb a.i./acre to semi-aquatic areas. At 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 exhibited 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 likely to dissipate through leaching. Field 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. 

Additionally, 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 owing 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 uses 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 invertebrates is uncertain. Chronic 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 plant seedling 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 listed 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 LC50) is limited by its solubility (i.e., 0.120 mg/L) as none of the studies were able to 

establish a definitive LC50. Therefore, acute 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 brackets 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. Under the most conservative exposure scenario and residue assumptions, chronic 

exposure estimates are 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/marine 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, sediment 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 are 3.21 μg/L, the Agency considers the predicted exposure to be insignificant. 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 orders of magnitude greater than peak 

EECs, and PT-1-3 and PT-1-9 are not acutely toxic at their 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 absence 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 available 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 LC50 was still nondefinitive.

Reduction of EEC by reducing 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 no 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 LD50 = 2,510 mg a.i./kg-bw) and the highest value in the avian sub-acute dietary 

study (i.e., acute LC50 = 2,023 mg a.i./kg-diet) represent the avian acute endpoints. The resulting 

dose-based and dietary-based acute RQs for all size and dietary classes, based on the upperbound 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 chronic 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 LD50 = 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 chronic 
Page 50 of 64

endpoints. 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 were identified 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 hexythiazox-treated pollen into the 

hive for consumption by larval stages. Therefore, risk to non-target terrestrial invertebrates is 

considered uncertain.

 

Direct 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 25% 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 is limited considering that 

eight of 10 tested crop species in the Tier I seedling emergence test did not exhibit phytotoxic 

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

this is a line of evidence indicating 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 listed 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 under 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 continued existence of a listed species means "to engage in an 

action that reasonably would be expected, directly or indirectly, to reduce appreciably the 
Page 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 registration 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 species 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 renewed registration of hexythiazox on 

agricultural use sites. It 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-located 

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 treated 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 with 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 

with 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 locations of these species, and the 

locations of use sites are considered to determine the extent to which screening assumptions 
Page 52 of 64

regarding an action area apply to a particular listed organism. These subsequent refinement steps 

will consider how this information 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 hexythiazox 

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 terrestrial 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 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 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 section 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 endangered 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 Hexythiazox.

Listed Plant Taxon Potential Direct Effects

Terrestrial and semi-aquatic 

plants – monocots and dicots Uncertain1

Aquatic nonvascular plants No

Aquatic vascular plants No

Listed Animal Taxon Potential Direct Effects

Acute Chronic

Terrestrial invertebrates Uncertain2 Uncertain2

Mammals No3 No3

Birds No3 No3

Reptiles No3 No3

Amphibians No5 Uncertain4

Freshwater fish No5 Uncertain4

Freshwater invertebrates No5 Uncertain6

Mollusks Uncertain7 ND

Estuarine/marine fish No5 Uncertain4

Estuarine/marine invertebrates No5 Uncertain6

ND = Not determined 1 Tier I terrestrial plant testing is incomplete; tier II seedling emergence data is not available for two species that demonstrated effects greater than 

25% in tier I testing. Only one tier I vegetative vigor study used TEP for testing (all other 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 high 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 formulated 

hexythiazox is expected to be below the LOC. 

4 No chronic fish toxicity studies have been submitted. Fish are surrogates for aquatic phase amphibians. 5 Solubility issues confound the results of acute toxicity testing; no definitive LC/EC50 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 observed from 

chronic pelagic invertebrate testing raise chronic risk concerns for sediment dwelling aquatic invertebrates.

7 No acute bivalve studies have been submitted
Page 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 Thieme 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 Pears. Environ Entomol 15 (5): 1047-1049.

United States Environmental Protection Agency. 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

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

Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide 

Programs. Washington, D.C. January 23, 2004.

USEPA, 2007. Problem Formulation for Hexythiazox in Hexythiazox Summary Document: 

Registration Review. Office of Pesticide Programs, January, 2007.

USEPA, 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

USEPA, 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 

Programs, October 6, 2009.

USEPA. 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, 2010a. 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

USEPA. 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) version 1.11. 

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

U.S. EPA. 2012a. Incremental Ecological Risk Assessment for New Uses on Alfalfa, Timothy, 

Eggplant, and Peppers. Environmental 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/models/terrestrial/

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

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

D404023.

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.txtmodified 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 Day60 Day90 DayYearly

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 2.568

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 5.444 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 2.99 2.909 2.682

1990 3.352 3.227 2.987 2.9 2.841 2.669

Sorted results

Prob. Peak 96 hr 21 Day60 Day90 DayYearly

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 3.187
Page 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

0.419354838709677 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

0.580645161290323 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/L
Page 58 of 64

Koc Koc 6188 mg/L

Photolysis half-life kdp 17 days Half-life

Aerobic Aquatic Metabolism kbacw 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

Application 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 assessments 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 several 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

MRID 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 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 test levels. Final hexythiazox 

concentrations had declined to 10%-59% of initial measured 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. Therefore, this 

study has been downgraded from “acceptable” to “supplemental”; and the nondefinitive LC50 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 00260839. 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 measured 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 LC50 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 concentration which was 
Page 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) was 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 

concentration 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 hexythiazox transformation product PT-1-2. The 

48-hr EC50 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 hexythiazox transformation product PT-1-3. The PT-1-3 EC50 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 hexythiazox transformation product PT-1-9. The PT-1-9 EC50 was 

determined to be greater than the limit of solubility (7.9 mg/L). This study is 

classified as supplemental.

Chronic Freshwater Invertebrates
Page 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 missing 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, cleaning 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 effects 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, will 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 was significantly reduced compared to the negative control at 

concentrations as low as 54 ppb, resulting in an inhibition 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 seven test 

concentrations ranging from 0.1-6.4 mg/L. Both a negative and dispersant 

(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 Estuarine/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 solubility; 

however, filters were used to prevent precipitate from entering the test chambers 

and final test concentrations were similar to initial test concentrations. The LC50

is non-definitive; >110 μg a.i./L.
Page 62 of 64

MRID 48114001. This chronic flow-through mysid 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 F0 and F1 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 67% at this 

LOAEC. The NOAEC for reproductive effects seen in this study was 17.2 ppb.

No data is available 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 for 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 this 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 EC50 value is considered to be the limit of 

solubility. 

MRID 48910706. This recently submitted study evaluated response of freshwater 

nonvascular green algae Desmodesmus subspicatus to seven concentrations of 

hexythiazox. The EC50 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 

(mg/L)

Thiazoldinones

(mg/L)

Monothiocarbamates

(mg/L)

Carbonylureas

(mg/L)

Neutral

(mg/L)

Parent > 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 

(mg/L)

Thiazoldinones

(mg/L)

Monothiocarbamates

(mg/L)

Carbonylureas

(mg/L)

Neutral

(mg/L)

Parent >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

(mg/L)

Thiazoldinones

(mg/L)

Monothiocarbamates

(mg/L)

Carbonylureas

(mg/L)

Neutral

(mg/L)

Parent > 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/a
Page 64 of 64

Algae Acute

Chemical Endpoint 

(mg/L)

Thiazoldinones

(mg/L)

Monothiocarbamates

(mg/L)

Carbonylureas

(mg/L)

Neutral

(mg/L)

Parent > 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