OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460



### PC Code: 129701
DP Barcode: 425426

Date: 10/1 9 /2015



### MEMORANDUM

Subject: Hymexazol : Ecological Risk Assessment for Registration Review

To: Caitlin Newcamp, Chemical Review Manager
Ricardo Jones

, Chemical Review Manager

R isk Manage ment and Implementation Branch 1
Pesticide Re

- evaluation Division

Through: Dan a Spatz, Branch Chief
Environmental Risk Branch 3
Environmental Fate and Effects Division

From: Tanja Crk, Biologist

James K. Wolf, PhD. Environmental Scientist
Environmental Risk Branch 3
Environmental Fate and Effects Division

Peer Review: Melissa Panger, Ph.D., Senior Scientist

Rosanna Louie

- Juzwiak, RAPL
Environmental Risk Branch 3
Environmental Fate and Effects Division

This memorandum transmits the Environmental Fate and Effects Division’s (EFED) ecological risk
assessment for hymexazol

. The results of this risk assessment indicate:

For seed treatment on sugar beets :

• Growth effects to non

- target plants are not expected.

• Effects of mortality, growth, and reproduction of fish, aquatic

- phase amphibians, and aquatic invertebrates are not expected.

### • Risk of mortality and reproductive effects have been identified for mammals and birds. Although t his chemical is slightly toxic to mammals and birds on an acute oral basis and practicall y non

- toxic to birds on an acute dietary basis , the LOC exceedances identified in
this assessment can be attributed to potentially high application rate s ( i.e., 0.15

- 1.25 lb a.i./A), which are based on the seed treatment application and seeding rate. For details,
see Risk Characterization Section and Appendix E

.

• Despite risk identified for birds ( i.e. , considered surrogates for terrestrial

- phase amphibians and reptiles), the effects of mortality, growth, and reproduction of terrestrial

phase amphibians and reptiles are not expected on the basis of low likelihood of seed consumption.

• Risk to t errestrial invertebrates is not expected based on toxicological data from the European Food Safety Authority (EFSA). The data was submitted by the registrant upon

r equest for this risk assessment and has been reviewed for this risk assessment

.

The EPA reviewed honey bee studies an d the EFSA (2010) report cite acute oral and contact honey bee endpoints as LD 50 

### >100 mg/bee and LC 50 

### >100 mg/bee, respectively. Hymexazol is registered for use as a fungicide and is applied via seed treatment on sugar beets. The compound is systemic 1 

### but the mode and extent of systemic transport as well as persistence specifically in

sugar beet plants is expected to be minimal

-- f or details, see the general explanation of anticipated systemic transport of hymexazol in plants in S ection I.A. below.

The biennial crop needs the first year to produce sugar and second year to use the sugar for flower production. Therefore, sugar beets g rown for their roots (for sugar) do not have flowers for pollination. However, sugar beets can also be grown for seed production and g iven that the

sugar beet is both wind and insect pollinated

, data to assess the effect on pollinators is

recommended. Furthermore, sugar beets are attractive via nectar to honeybees and other bees.

Ho wever, given the rapid metaboliz ation of the parent to CO 2 

### and incorporation into sugars in the plant (MRID 42826314) and flowering time a year after planting , only t he fol lowing studies on the adult honey bee would be needed in order to conduct a risk assessment for honey bees taking into account the seed treatment use :

1. A cute oral 2 

### toxicity to adult honey bees (Non

- guideline, OECD TG 213)

2. Acute contact 2 

### toxicity to adult honey bee (OCSPP Guideline 850.3020)

At this time, data from these studies has been incorporated in this assessment on the basis of

EFSA 2 

### and EPA reviews

.

1 http://sitem.herts.ac.uk/aeru/iupac/Reports/388.htm “Systemic, inhibits fungal growth by inhibiting nucleic acid synthesis (DNA / RNA synthesis).”

2 Report available online: http://www.efsa.europa.eu/en/scdocs/doc/1653.pdf

### I. EXECUTIVE SUMMARY

A. Nature of the Stressor

Systemic properties of hymexazol

Hymexazol is a systemic fungicide, or more specifically, a partially (locally) systemic fungicide. It is rapidly translocated and has locally systemic distribution properties (Ypema, 2003). The chemical has upward properties (Mueller and Bradley, 2015) a nd is taken up by roots and rapidly transformed into glucosides for fungitoxic activity or stimulation of lateral root hair development in seedlings (Ypema, 2003).

Hymexazol is registered as a seed treatment to control soilborne pathogens on sugar beet such

as Aphanomyces spp root rot and Pythium spp root rot. The fungicide is active for a few weeks after planting, plays an important role for early season control, does not protect against chronic root rot, and does not result in detectable residues in m ature sugar beet roots (Harveson et al., 2007). Though the two pathogens listed on the label cause root rot, implying that hymexazol ought to be present in the plant after germination for protection against the disease, a metabolism in sugar beets study (MRID 42826314) on the determination of food/non

- food use, finds substantial evidence that hymexazol rapidly metabolizes (degrades) to CO 2 

### in the plant and subsequently gets incorporated into sugars. In the study plants were treated with 45 g Tachigaren 70WP/kg raw seed; total radioactive residues were 0.006

- 0.007ppm in aerial samples and 0.015

- 0.022 ppm in roots. The study evaluation suggests that greater than 85% of the radioactivity in the sugar bee ts grown from hymexazol treated seeds was present due to incorporation of 14 

### C

CO 2 

### into the natural sugars of the beet. As a result of this study, the Chemistry Branch Tolerance Support ( CBTS , extant at the time within the Health Effects Division) determine d that the sugar beet use of hymexazol is a non

- food use.

II. PROBLEM FORMULATION

a. Pesticide Type, Class, and Mode of Action

Hymexazol ( 5

- methyl

- 3(2 H )

- isoxazolone; CAS No. 10004

- 44

- 1) is a fungicide belonging to the isoxazole chemical family. H ymexazol affects nucleic acid synthesis, possibly inhibiting DNA/RNA. FRAC 3 

### has classified this MOA as a nucleic acid synthesis inhibitor. H ymexazol is registered as a fungicide, but it may also function as a growth rate regulator 4

, 5



### . The parent hymexazol is assume d to be the only stressor as the degradation products were shorted lived

.

3 Fungicide Resistance Action Committee

– www.frac.info

4 http://www.alanwood.net/pesticides/hymexazol.html

5 Payne and Williams, 1990.

### b. Overview of Pesticide Use and Usage

Hymexazol is used as a seed treatment for sugar beet ( Beta vulgaris ) seeds to protect against

seed and seedling diseases such as Aphanomyces spp. and Pythium spp

.

Hymexazol Usage Based on the Screening Level Usage Analysis memorandum produced by the Biological and Economical Analysis Division (EPA, June 11, 2014), an average of 3,000 pounds of hymexazol for
seed treatment was used annual ly

, with an average of 15 percent crop treated and a maximum of 25 percent crop treated (reporting years 2004

– 2012).

Sugar beet cultivation is found in many parts of the US but appear to be most prominent in California, Colorado, Michigan, Montana, Minneso ta, Nebraska, North Dakota , Oregon, and Washington. Because sugar beets are grown nationwide, it is believed that hymexazol could be applied anywhere in the country. The acres of sugar beets plant ed and harvested for several years from the USDA National A gricu l tural Statistics Service (USDA, NASS, 2015 6 

### ) are

summarized in Table 1

.

Table 1. Acres of sugar beets harvested in 2007, 2012, 2014, and 2015 and sugar beets planted in 2014 and 2015.

State Acres
Harvested a


### 2012 Harvested a


### 2007 Planted

2014 b 

### Harvested

2014 b 

### Planted

2015 b 

### Harvested

2015 b

, c


### California 27,193 42,984 24,300 25,000 22,600 25,000
Colorado 30,553 29,235 29,600 27,000 29,300 26,700
Idaho 184,510 163,598 171,000 168,000 169,000 167,000 Michigan 156,447 150,054 151,000 154,000 150,000 153,000
Minnesota 480,847 485,650 440,000 430,000 434,000 416,000

Montana 45,807 47,533 45,100 44,700 44,400 44,400
Nebraska 51,671 44,938 49,000 48,000 45,900 46,500
North Dakota 227,771 245,735 216,000 224,000 215,000 218,000 Oregon 11,731 11,232 67,000 12,700 6,500 12,600

Vermont 6

- - - - - Washington

- 2,076 Wyoming 31,302 30,782 30,700 31,000 30,000 30,800 Total for sugar d 

### 1,249,481 1,253,817 1,163,400 1,644,000 1,146,700 1,140,000 Pennsylvania 2,344 2,510 Washington 1,351

- Total for seed d 

### 4,588 3,199

a http://www.agcensus.usda.gov/Publications/2012/Full_Report/Volume_1,_Chapter_2_US_State_Level/st99_2_025_025.pdf

b http://usda.mannlib.cornell.edu/usda/current/Acre/Acre

- 06

- 30

- 2015.pdf

c Relates to year of intended harvest for fall planted sugar beets in central California and to the year of planting for overwintered sugar beets in central and southern California.

d Totals may not add up because some states information wa s w ithheld to avoid disclosing data for individual operations

6 http://www.nass.usda.gov/Data_and_Statistics/index.asp

### The US Geological Survey as part of the NAWQA program 7 

### reported national

- level pesticide usage data for hymexazol available for a three year period (2009

- 2011). Figure 1 shows the use

areas for 2010.

Figure 1. Hymexazol usage map for 2010 and by use year for 2009 to 2011 (USGS, 2014).

Hymexazol is not applied to the soil before sowing nor are seeds treated in the field. Sugar beet seeds are treated and pelletized in commercial operations and then sown through broadcast spreader or seed drill.

Application information for hymexazol is su mmarized in Table 2

. Hymexazol is formulated as a wettable powder (70% active ingredient) in the fungicide seed treatment

– Tachigaren  70 WP (EPA Reg. No. 48210

- 1). The application rate for hymexazol according to the label is 45 to 90

7 http://water .usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=2011&map=HYMEXAZOL&hilo=L&disp=Hy

mexazol

### grams of Tachigaren 70 WP (hymexazol 70% active ingredient, a.i.) to 100,000 pelleted sugar beet

seeds

, or 31.5 to 63.0 gram a.i. to 100,000 seeds [0.315 to 0.63 mg a.i./seed] . The mass of the 100,000 sugar beet seeds is about 1 kg (45,359 seeds per pound). Single application rates for hymexazol in lb a.i./A (needed for EFED exposure models) for seed treatment were not provided on the labels; however, EFED was able to convert the rates from lbs a.i./kg seed to lb a.i./A and the range is 0.126 to 1.25 pounds active i ngredient/acre (lb a.i./A), depending upon sugar beet

see d ing rates ( Table 3 ).

Table 2 . Maximum Hymexazol Use Rates on Sugar beets (EPA Reg. No. 48210

- 1)

Seeding

Rate a (lb seed/A) Max. Rate per App (lb a.i./kg seed) b Max. App

Rate (lb a.i./A)

NON

- FOOD/NON

- FEED USES

2.0 0.139 0.126

3.6 0.139 0.23

4 0.139 0.25

4.8 0.139 0.30

5 0.139 0.32

5.5 0.139 0.35

8 0.139 0.50

10.0 0.139 0.63

15.0 0.139 0.95

19.8 0.139 1.25

a Base d upo n seeding rates given in Table 3

. b (0.139 lb a.i./kg seed or 0. 0 63 lb a.i./lb seed)



### The seeding rate (lb seed/A or # of seeds/A) varies from region or state and has changed over time ( Table 3 ). Seed planting depth also varies from location to location on the basis of the moisture content in the soil needed for seed germination

. Tables 2 and 3 capture the range of seeding rates found in the literature. However, the standard seeding rates used for terrestrial exposure calculations are found in T

- REX and based on input from BEAD. These include seeding rates at 4.8 lb seed/A for sugar beets and 19.8 lb seed/A for sugar beet seed production.

### Table 3. Sugar beet seed source, depth of seeding, seeding rate, and application methods.

Sugar beet seed

Source See ding Depth (inch) Seeding Rate (lb seed/A or #seed/A)

Khan a 1 to 1.25 13,068

– 53,894 #/A

Bucklunch b 0.5 to 1.5 10

– 15 c lb seed/A

5

- 10 lb seed/A

8

– 10 lb seed/A b

, c , d

CO Crop Profile d 0.75 to 1.25 55,000 #/A

Sugar beet production e 0.75 6

- 10 lb seed/A

Seedland f 0.25 to 0.5 8

- 10 lb seed/A

3

- 4 lb seed/A

Handcock seed

company g 0.25 to 0.50 10

- 15 lb seed/A

OR sugar Beet production h 0.75 4

- 10 lb seed/A

2015 Sugar beet
Production i (ND and MN) 1.0 to 1.25 81,463 #seed/A; 22”row

3.5 inches between seed

Sugar beet j 1.5 1

– 2 lb seed/A

Holly Seed k 100,000 seeds/pellet

USEPA, 2011 l 34,848 to 435,600 seeds/A 1.25 to 4.0 lb seed/A

a Khan 2013: http://www.sbreb.org/production/2013/2013SBProductionGuide.pdf

b http://www.bucklunch.com/docs/bucklunch_brochure.pdf ;

c http://www.bucklunch.com/docs/bucklunch_plantinstruct.pdf '

d http://www.ipmcenters.org/cropprofiles/docs/cosugarbeets.pdf

e http://cropandsoil.oregonstate.edu/system/files/classes/css460

- 560/Chapter_9.pdf

f http://www. seedland.com/mm5/merchant.mvc?Screen=CTGY&Store_Code=Seedland&Category_Code=WG

- BEETS

g https://hancockseed.com/seed

- varieties

- 241/sugar

- beets

- seed

- 668/

h Chastain T.G. http://cropandsoil.oregonstate.edu/system/files/u528/Sugar%20Beet%20Seed%20Production.pdf

I htt p://www.smbsc.com/pdf/2015SBGuide.pdf

j http://corn.agronomy.wisc.edu/Crops/Sugarbeet.aspx

k http://www.hollyseed.com/seed/seed

- packaging

- sizing

l USEPA, 201 1

. Becker, J. and S Ratnayake. 2011. Acres planted per day and seeding rates of crops grown i n the United States. OCSPP/BEAD March 24, 2011.



### c. Previous Ecological Risk Assessments and Evaluations

Hymexazol was registered in 1995 as a seed treatment for sugar beet (USEPA 1995a, DP 209885 ; USEPA 1995b, DP 209851, 205149 

### ). The concentrations of hymexazol (peak to 54

- days) were < 6 μg/L (ppb). The estimates were based on 0.126 lb a.i. /A, assuming a typical planting (or seeding) rate of 1.5 to 2.0 lbs of seed per acre. The environmental exposure concentrations (EECs) in

### aquatic systems were estimated with the Tier 1 GENEEC model, Version 1. A seed treatment assessment using the analysis currently available in T

- REX was not conducted, nor was the Seed Consumption A pproach (SCA) available at the time of this earlier assessment. Toxicity data used
for this PRA on the passerine (acute oral), the chronic avian

, and chronic mammalian studies were
not available for this earlier assessment. Hymexazol did not reach the acute Levels of Concern (LOCs) for birds, mammals, freshwater fish and freshwater invertebrates. No study was available
to evaluate th e risk to estuarine and marine animals, but i t was noted that the exposure was limited by the use pattern, together with the low aquatic toxicity of hymexazol. Although the risk could not be quantitatively evaluated, it was conclude d that no estuarine data were required. In addition, the label cautions phytotoxicity could occur when use rates are >45 g of product per
seed. The risk to non

- target plants could not be evaluated due to a lack of data. At that time, it
was concluded that a ll RQs were well below the LOCs for endangered species for which data had been submitted on birds, mammals, fish and invertebrates.

A registration review preliminary problem formulation was completed in 2010 (USEPA 2010 a ).

III. Risk Hypothesis and Conceptual Model

a. Measures to Evaluate Risk Hypotheses

M easures of exposure are based on terrestrial and aquatic exposure models 8 

### that estimate d
environmental concentrations (EEC) of hymexazol (parent) using maximum labeled application

rates. T he T

- REX model (version 1.5.2) is used to produce terrestria l EECs on wildlife food items.
The TerrPlant model is used to estimate exposure to non

- target plants. Because the use is a seed treatment, spray drift is assumed to be zero for both broadcast with incorporat ion or drilled seeding

. Th e Surface Water Concentration Calculator (SWCC 9 

### ; version 1.106) is used to produce

EECs for aquatic exposure

. Though the STIR model can be used to account for potential inhalation exposure, the model was not used in this assessment because inhalation is not anticipated to be a significant route of exposure from the seed treatment use; the seeds are expected to be coated and inhibit volatilization of the active ingredient leading to ingestion as the primary route of

exposure.

Measures of effect are obtained from a suite of studies conducted with a limited number of surrogate species. The lowest toxicity endpoints for the most sensitive surrogate test species are
used to estimate treatment

- related effects on growth, reproduction and/or survival.

8 http://www.epa.gov/pesticides/science/models_pg.htm

9 http://www.epa.gov/oppefed1/models/water/index.htm#swcc

### b. En vironmental Fate an d Modeling Input Parameters

Physical/Chemical and Environmental Fate Properties

The p hysical/chemical properties are in Table 4 and the environmental fate properties of hymexazol are listed in Table 5

.

Table 4 . Select Identifiers and Physical and Chemical Properties of Hymexazol a

Parameter Value

Common name Hymexazol

Chemical name IUPAC: 5

- methylisoxazol

- 3

- ol

5

- methyl

- 1,2

- oxazol

- 3

- ol

CAS: 5

- methyl

- 3(2 H )

- isoxazolone

Pesticide type Fungicide

Chemical class Isoxazoles chemical group

CAS number 10004

- 44

- 1, assigned to the enol tautomer

Trade name Tachigaren®

Empirical formula C 4 H 5 NO 2

Chemical Structure

Molecular mass (g/mole) 99.09

Vapor pressure, at 25 ̊C 1.37 E

- 3 torr ( mm Hg )

Henry’s Law Constant 6.5 E

- 9 atm

- m 3 /mole*

2.7 4 E

- 9 atm

- m 3 /mole (calculated @ pH7)

Solubility in water (g/L) , 20 ̊C @ pH7 5.82 g/mL b (pH 3) 58.2 g/L

6.51 g/mL b (pH 7) 65.1 g/L (bold value used to calculate Henry’s constant

6.78 g/mL b (pH 9) 67.8 g/L
There appears to be a conversion error in one of the sources of solubility data as (e.g., 6.51 g/mL does not equal 65.1 g/L).

Log K ow 0.48

pK a 5.92

* Estimated via EPISuite

a MRIDs 428263

- 01/

- 02/

- 03. Reviewed 03/29/1995.

b Solubility in the Problem Formulation (02/16/2010) solubility was reported in g/m L however in other sources report solubility in g/L.

### Environmental Fate/Exposure Summary

F our Guideline studies were required w hen hymexazol (Tachigaren ® 

### 70 WP) was initially registered

, in 1995

, as a fungicidal seed treatment, pelletized for field

- planted sugar beet seeds.
The guideline studies were hydrolysis (161

- 1), aerobic soil metabolism (162

- 1), anaerobic soil metabolism (162

- 2), and adsorption/desorption (mobility, 163

- 1 ) ( Table 5 )

. These studies were discussed in detail for the new chemical registration action (D209851; 04/28/95). Since then, n o additional information has been submitted. T he environmental fate of hymexazol is summarized

in Table 5 b ased on submitted fate and transport studies

.

Table 5 . Select Environmental Fate Data for Hymexazol.

Environmental Fate Property Value Comments MRI D Hydrolysis (t 1⁄2 

### ) Stable @pH 5,7, 9 and 25 to 70°C 42826311 Aerobic Soil Metabolism (t 1⁄2 

### ) 7.7 days SFO a 

### (Single First Order) 42826312 Anaerobic Soil Metabolism (t 1⁄2 

### ) 1.72 days SFO a 

### (Single First Order) 43253801 Adsorption (mL/g or mL/g

oc 

### ) K d 

### K
oc 

### <0.10 9.1

<0.10 11.8

0.25 193
0.423 18

0.526 66 AZ (SiCLm); K

oc 

### assume K d 

### = 0.1 CA (SLm); K

oc 

### assume K d 

### = 0.1 Plainfield ( S and) Kewaunee (Clay) Mississippi (SiLm) 42826313

Octanol/water Partition
Coefficient (K

ow 

### ) 3.0 ( Log K
ow 

### = 0.48 ) D209851 b

a USEPA, 2014. Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half

- life Values and Characterizing Pesticide Degradation (Nov. 26, 2014) OPP/EFED Arlington, VA.

b Clem, A. 1995. New Chemical Registration of the Fungicide Hymexazol. (D209851 04/28/95)



### Biotransformation in aerobic and anaerobic soils is the major route of dissipation of hymexazol. Hymexazol is stable to abiotic hydrolysis. Biodegradation is a relati vely rapid process with half

life of less than 12 days under aerobic conditions and less than 2

- days under anaerobic
conditions. The chemical biodegrades through r ing

- cleavage produc ing degradates that are mostly of lower molecular weight and are associate d to naturally occurring products (e.g., acetoacetamide, crotonic acid, acetoacetic acid). These chemical species are short lived and

transient. The end products are carbon dioxide under aerobic conditions and methane under
anaerobic conditions. The metabo lite 5

- methyl

- 2(3H)

- oxazolone was proposed as a possible, intermediate product in the degradation of hymexazol to CO 2 

### , where about 1 to 2% of applied was detected, but was not identified in the aerobic soil metabolism study (MRID 42826312).

Batch

- equilibr ium sorption studies indicate that hymexazol is very mobile. Mobility increases with pH, as expected from a weak acid with a pK a 

### of 5.92. The K d 

### values ranged from < 0.1 to 0.526 mL/g and calculated K oc 

### values of 18 to 193 mL/g oc 

### indicating it is high to very high
mobil ity 10



### .

10 Bradbury, S. 200 6 . Standardized Soil Mobility Classification Guidance.

### Possible volatilization of parent from dry soil is also suggested by the vapor pressure (1.37 X 10

- 3 

### torr) and Henry’s Law Constant value ( 2.74 x 10

- 9 

### atm

- m 3 

### /mol )

.

Hymexazol does not appear to have a potential to bioaccumulate in fish. Its n

- octanol partition coefficient is very low (K ow 

### = 3.0 ).

Monitoring Data Detections in Environmental Media

The Agency was unable to locate or identify any monitoring data for hymexazol in the USGS
NAWQA 11 

### data base, USDA Pesticide Data Program (PDP) 12 

### data b ase, and the California Department of Pesticide Regulation Surface Water Data Base 13



### .

Ecological Effects Characterization

Effects to Aquatic Organisms

A summary of the most sensitive aquatic toxicity data for hymexazol is provided in Table 6

. Data indicate that hymexazol is practically non

- toxic to freshwater fish and slightly toxic to invertebrates on an acute exposure basis. There are no available chronic toxicity data for fish
and invertebrat es, or toxicity data for estuarine /marine anima ls or marine non

- vascular plants

. The toxicity to these species exposed to hymexazol is uncertain

.

Table 6. Aquatic Toxicity Profile for Hymexazol

.

Taxon Exposure
Duration Most Sensitive Species Tested Toxicity Value Toxicity Category MRID /

Classification

Freshwater
Fish Acute Rainbow trout Oncorhynchus mykiss LC 50 >100 m g a.i. /L
No Effects Practically non

toxic 42960005 (acceptable; limit test)

Chronic EFSA Data Available Only. See risk characterization section.

Estuarine/

Marine Fish Acute /

Chronic No data available

Freshwater
Invertebrates Acute Water Flea
Daphnia magna EC 50 = 30.8 m g a.i. /L Slightly toxic 42960007 (acceptable)

Chronic EFSA Data Available Only. See risk characterization section.

Estuarine/

Marine
Invertebrates Acute /
Chronic No data available

11 USGS National Water Quality Assessment Data War ehouse (07/20/15)
NAWQA http://cida.usgs.gov/nawqa_public/apex/f?p=136:23:0:QUERY:NO

12 USDA, PDP http://www.ams.usda.gov/AMSv1.0/ams.fetchTemplateData.do?template=TemplateO&navID=PDPOviewBox2Link6& rightNav1 =PDPOviewBox2Link6&topNav=&leftNav=ScienceandLaboratories&page=PDPTestingHistory&resultType=&acct=pestcddataprg

13 CDPR, Surface Water Database (SURF) http://www.cdpr.ca.gov/docs /emon/surfwtr/surfdata.htmTaxon Exposure
Duration Most Sensitive Species Tested Toxicity Value Toxicity Category MRID /

Classification

Vascular plant Acute Duckweed Lemna gibba EC 50 = 7.9 mg a.i. /L

NOAEC < 3.1 mg a.i. /L

EC 05 = 1.1 mg a.i. /L Not applicable 43926302 (supplemental 1 )

Non

- vascular plant Acute Cyanobacteria Anabaena flos

- aquae 2 EC 50 = 23.39 mg a.i. /L

NOAEC = 5.79 mg a.i. /L

Reduced yield (for pH

adjusted samples) Not applicable 49021702 (acceptable)

1 Data on biomass was not available

2 Data on A. flos

- aquae, P. subcapitata (formerly known as S. capricornutum ), and N. pelliculosa were submitted. However,
data on the marine diatom S. costatum are not available

.



### Effects to Terrestrial Animals and Plants

A summary of the most sensitive terrestrial toxicity data for hymexazol is provided in Table 7

. The data indicate that hymexazol is slightly toxic to mammals and is slightly toxic to practically nontoxic to birds on an acute exposure basis. A second avian reproduction study was reviewed
for this assessment (MRID 49268101) and is reported below the avian reproduction study that
was used in risk estimation ( i.e., MRID 4871 6602)

. The EPA reviewed honey bee studies and the European Food Safety Authority (EFSA) risk assessment indicate acute oral and contact honey bee toxicity as LD 50 

### > 100 μ g /bee and LC 50 

### > 100 μ g/ bee, respectively, for the hymexazol technical.

Table 7. Terrestrial Toxicity Profile for Hymexazol

.

Taxon Exposure
Duration Most Sensitive Species Tested Toxicity Value Toxicity Category MRID
Reference

Mammals 1 Acute

Rat Rattus norvegicus ♂ LD 50 = 1600 mg a.i. /kg bw
Mortality Slightly

toxic 42960008 (acceptable) [TGAI: 99.1% a.i. via gavage]

Chronic NOAEL = 100 mg/kg

- bw/day LOAEL = 500 mg/kg

- bw/ day Reduced fetal weight,
evidence of other developmental abnormalities N/A 42826307 [ter atogenicit y study w/ TGAI:

92.7% a.i. via

gavage ]

Acute Oral Zebra Finch Taeniopygia guttata (body weight: 12.7 g) 2 LD 50 = 827 mg a.i./kg bw Mortality Slightly

toxic 49018701 (supplemental, for quantitative use )

Acute Dietary Bobwhite quail
Colinus virginianus LC 50 >5200 mg a.i./kg diet Practically

nontoxic 42960004 (acceptable)

Chronic Bobwhite quail Colinus virginianus NOAEC = 385 mg a.i./kg

- diet LOAEC = 962 mg a.i./kg

- diet Egg shell thickness N/A 48716602 (acceptable)

Mallard duck

Anas platyrhynchos NOAEC = 902 mg a.i./kg

- diet LOAEC = 4467 mg a.i./kg

- diet Eggshell thickness N/A 49268101 (supplemental 3 )

Terrestrial

Insects Acute Honey bee Apis mellifera LD 50 >100 μ g /bee

LC 50 >100 μ g /bee Practically

nontoxic 49718601
(supplemental, quantitative 4 )Taxon Exposure
Duration Most Sensitive Species Tested Toxicity Value Toxicity Category MRID
Reference

Terrestrial
Plants

- Seedling Emergence Survival
and growth Onion (monocot) Allium cepa IC 25 = 174 lb a.i. /A
NOAEC = 152 lb a.i. /A Reduced fresh weight (biomass) N/A 44071301 to
44071310
(acceptable 5 ) Cabbage (dicot)
Brassica oleracea IC 25 = 35 lb a.i. /A

NOAEC = 16 lb a.i. /A Reduced fresh weight (biomass)

Terrestrial
Plants

– Vegetative Vigor Survival
and growth Ryegrass (monocot) Lolium perenne IC 25 = 437 lb a.i. /A
NOAEC = 166 lb a.i. /A Reduced fresh weight (biomass) 44071311 to

44071320 (acceptable) ; 44071319 (supplemental 6 )

Tomato (dicot) Lycopersicon
esculentum IC 25 = 63.5 lb a.i. /A

NOAEC < 16.2 lb a.i. /A (IC 05 = 32.1 lb a.i. /A) Reduced dry weight 48677801 (supplemental, for quantitative use )

1 An acute oral (gavage) toxicity study in rats using the TEP (70% a.i.; MRID 42956301 ) is also available, where the male LD 50 :
27 00 mg a.i./kg

- bw. Furthermore, a rat 2

- generation reproduction study (MRID 42826309) suggests effects to post

implantation survival rate and l itter size at the high dose (LOAEL: 159 mg a.i./kg

- bw); the NOAEL in the study is 31 mg a.i./kg

bw. However, the developmental NOAEL (100 mg/kg/day) is protective of the reproductive effects at 159 mg/kg/day in the

2

- generation study

.
2 The body weight cited here was used in T

- REX. It is based on the mean of mean body weights taken in the control from day 0, day 7, and day 14 for both males and females. The means for the 5 control males at those respective time steps are: 12.8g, 13.4g, 13 .6g; the means for the 5 control females are: 11.9g, 12.3g, 12.2 grams. The average of these values is 12.7 grams.

3 Quantitative for eggshell thickness only.

4 The honeybee study did not include a negative control. Treatment data were compared to a solvent control.

5 Upgraded from supplemental per US EPA 2010b memo

. 6 Tomato plant only because the plants were not cultivated under optimal growing conditions.



### IV. ANALYSIS

a. Exposure Modeling

Model inputs include values for certain physical

- chemical propertie s of the pesticide, application practices, and crop agronomic information.

The input parameters used in this aquatic and terrestrial modeling assessment are selected from
the environmental fate data submitted by the registrant or available in ope n literature or estimated ( following EFED Model Input Guidance )

. Input parameters were prepared in
accordance with US EPA

- OPP EFED water model parameter s election guidelines, Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides 14



### . Detailed information about the water models, selection of input parameters and sce narios can
be obtained from http://www.epa.gov/oppefed1/models/water/index.htm

.

14 Parameters are selected as per Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of

Pesticides; Version 2.1, October 22, 2009.

### Aquatic Mo d eling

Potential aquatic exposure ( estimated environmental concentration, EECs) were estimated using

the Surface Water Concentration Calculator (SWCC; Version 1.106, 05/22/2014) for surface

water . The SWCC simulate s the fate and transport of pesticides on the agricultural field and the fate and resulting daily concentrations of pesticides that reach an adjacent water body through
runoff and erosion . S pray drift is assumed to be zero for treated seeds

.

Surface water s imulations are based on crop

- specific scenarios developed to represent

e nvironmental conditions at sites with a generally high runoff vulnerability. For this assessment the standard Minnesota sugar beet scenario was used. Aquatic ecological exposure is est imated using the “standard pond” scenario based on a 10

- ha field bordering a 1

- ha water body, 2

- m deep (20,000 m 3 

### ) with no outlet

. Weather and agricultural practices are simulated for 30 years so that
the 10

- year exceedance probability at the site can be e stimated. The simulation was generated using 30 years of meteorological data, encompassing the years from 1961 to 1990.

Aquatic Model Inputs

Th e hymexazol is applied to the seed and the seed is broadcast with incorporat ion or drill ed in by ground equipment

. The date of application is assumed to be 7 days before crop emergence

which is defined in each scenario. Spray drift is assumed to be zero, since the pesticide is applied

to the seed. Because the label only specifies a maximum rate per 100 kg o f treated seed, a range of seeding rates were considered, because of the range of sugar beet seeding rates (Table 3). The seeding rate (lb seed/A) therefore will influence the “hymexazol” application rate. There is also variability in the “pelleting of see d” which can also influence application rates (i.e., seeding rates).

The aerobic soil metabolism and anaerobic soil metabolism half

- lives for modeling were obtained
using R Foundation for Statistical Computing (version 3.1.2 and xxDeg_08.13) following NAF TA 15 

### guidance

. The R statistics following the NAFTA guidance recommended using the SFO (single first order degradation model). T he selection and procedure for selecting model input parameters followed EFED guidance 16



### . Since no seed leaching study has been submitted, EFED assume d that 100 percent of the hymexazol applied to the seed was available for leaching and runoff 17



### . Model inputs for the SWCC are summarized in Table 8

.

15 http://www.epa.gov/oppefed1/ecorisk_ders/degradation_kinetics/ftt_sop_using_nafta_guidance.pdf

16 http://www.epa.gov/o ppefed1/models/water/input_parameter_guidance.htm

17 USEPA, 2000. Standard Methods of Determining the Leachability of Pesticides from Treated Seed. (Keehner, D. 07/06/00).

### T able 8

. SWCC Input Parameters for Hymexazol.

Input Parameter Value Reference /Discussion

Molecular Weight (g/mole) a 99.09 USEPA, 2010 (D371500) b

Henry’s Law Constant a
(atm

- m 3 /mol) 2.7 4 E

- 9 Estimated from solubility of 65.1 g/L (@pH7, 20°C)

Vapor Pressure @ 2 5 oC (torr) a 1.37 x 10

- 3 USEPA, 2010 (D371500)

Solubility (mg/L) @ 25 ° C a 65,100 (65.1 g/L)

Aqueous Photolysis Half

- life [t 1⁄2 ](days) a 0 No data

Hydrolysis [t 1⁄2 ] @ pH 7 (days) a,c 0 S table

Aerobic Soil Half

- life [t 1⁄2 ] (days) a,c 23.1 7.7 x 3 (single value x 3) EFED Guidance

Aerobic Aquatic Half

- life [t 1⁄2 ] (days) a 46.2 ASM x 2 (23.1 x 2) EFED Guidance

Anaerobic Aquatic Half

- life [t 1⁄2 ] (days) 0 No Data

Organic Carbon Partition a,c
Coefficient (K oc ) (mL/g oc ) 59. 6 Average of 5 values (9.1, 11.8, 193, 18, 66)

Pesticide Application

Chemical Application Method I ncorporated 2 cm. Estimated from Table 3 w h ere 2 cm ≈
0.75 inch d

.

Application Date a,c

- 7 days (7days before) Days before emergence (scenario specific)

Application Efficiency a 1 EFED Guidance

Spray Drift (fraction) a 0 EFED Guidance

Application Rate (lb a.i/A) Range 0.126 to 1.25 See Table 2 ; depends upon seed treatment rate and seeding rate.

a Input for SWCC

b USEPA, 2010. Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Hymexazol (03/04/10; D371500).

c Input for PRZM

- GW

d Depth estimate also supported by https://www.hort. purdue.edu/newcrop/afcm/sugarbeet.html



### Modeling Results

Surface water EECs estimated by the SWCC for the MN sugar beet scenario are summarized in
Table 9
, assuming a 2

- cm seed incorporation depth

. Other incorporation depth s were evaluated and found to have no effect on the risk conclusion concerning the aquatic exposure

. For example, the peak EECs for the maximum rate with and a 1

- cm seed incorporation depth was 23.4 μg/L

. Example out put s are given in Appendix C

.

### Table 9 . Surface Water EECs for Aquatic Exposure: SWCC estimated Peak, 96

- hour, 21

- day and

60

- day average concentrations in standard farm pond for 6 rates and 2

- cm seed incorporation depth (estimated from Table 3 )

.

Scenario

MN Sugar beet s (lb seed/A) * Application

Rate (lb a.i./A) Peak 96

- hr 21

- day 60

- day

μg/L

2.0 0.126 1.39 1.37 1.33 1.15

3.6 0.23 2.54 2.51 2.42 2.11

4.8 0.30 3.31 3.27 3.16 2.75

5.0 0.32 3.53 3.48 3.36 2.93

5.5 0.35 3.86 3.81 3.68 3.21

8.0 0.50 5.52 5.45 5.26 4.58

10.0 0.63 6.99 6.91 6.67 5.81

19.8 1. 25 13.8 13.6 13.2 11.5



### * The seeding rate at 2 lb seed/A was used in a previous risk assessment. A current potential conservative estimate

from J. Becker, BEAD (email 03

- 12

- 15) is 3.6 lb seed/A. An ExpoSAC SOP (#15, 2004) cites a range between 2

- 8 lb seed/A. Estimates reported in T

- REX include 4.8 lb seed/A and 19.8 lb seed/A.



### Ecological Exposure

Terrestrial Exposure Modeling

- Animals

Terrestrial exposure estimates (EECs) for avian and mammalian risk assessments were derived using the T

- REX model (version 1.5.2). Table 10 presents five scenarios analyzed in T

- REX for
mammals and birds. Table 1 1 presents only the highest application rate analyzed in TerrPlant.
The foliar half

- life value has no effect on modeling EECs for seed treatment uses; thus, no value was entered for this parameter in T

- REX

. The highest seeding rate used was based on sugar beet
seeds planted for seed production ( i.e. , 19.8 lb seed/acre); the lo west seeding rate used was based on sugar beets presumably for root harvest ( i.e. , 4.8 lb seed/acre). The T

- REX equations for estimating residues on seeds assumes that the product is a liquid formulation ( e.g. , accounts for a default product density of 8.3 3 lb/gallon )

. The application rate units that are prompted for

in T

- REX are fl uid o unces / 100 pound weight, or fl. oz/cwt. In order to achieve the correct estimates, the application rate from the label ( for example

, the highest rate: 90 grams of product per kg of seed ) was used to derive an input of 138.8 fl

. oz

. /cwt (based on 1 g = 0.034 fl oz and 1 cwt sugar beet seeds = 45.36 kg )

. A complete description of the input parameters and output is
contained in APPENDIX B

. For reference, the values used are below:

Standard pellet

• High application (treatment) rate = 90 g TEP / kg

- seed (138.8 fl oz TEP/cwt)

• Low application (treatment) rate = 45 g TEP/kg

- seed (69.4 fl oz TEP/cwt )

Build

- up Pellet

• High application (treatment) rate = 30 g TEP/ kg

- seed (46.27 fl oz TEP/cwt) Seeding rates

• High seeding rate = 19.8 lb seed/A• Low seeding rate = 4.8 lb seed/A



### T able 10

. Intermediate Calculations for Seed Treatment Applications of H ymexazol U sing the

T

- REX Model

.

Animal

Size Scenario 1 (treatment rate/seeding rate) Maximum Application

Rate Maximum Seed Application

Rate Avian Nagy

Dose Mammalian Nagy Dose Available AI

(lbs a.i. /A) (mg a.i. /kg seed) (mg a.i. /kg

bw/day) (mg a.i. /kg

bw/day) (mg a.i. ft

- 2)

Small High app rate/ High seed rate 1.25 63,230 16 ,003 13,397

13.06 Medium 9 ,126 9,259

Large 4 ,086 2,147

Small High app rate/

Low seed rate 0.30 63,230 16,003 13,397

3.14 Medium 9,126 9,259

Large 4,086 2,147

Small Low app rate/ High seed rate 0.63 31,615 8,001 6,698

6.53 Medium 4,563 4,629

Large 2,043 1,073

Small Low app rate/

Low seed rate 0.15 31,615 8,001 6,698

1.57 Medium 4,563 4,629

Large 2,043 1,073

Small High app rate (build up) / Low

seed rate 0.10 21,078 5,335 4,466

1.05 Medium 3,042 3,087

Large 1,362 716

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)



### Plants
The model used to derive EECs relevant to terrestrial and wetland /semi

- aquatic plants for the registered uses of hymexazol for seed treatment is TerrPlant (version 1.2.2.). This model uses estimates of pesticides in surface water runoff based upon solubility ( i.e., 6 5

. 1 g/ L = 6.51 x 10 4 

### mg/L at 20 o 

### C and pH 7)

, highest single applica tion rate ( i.e. , 1.25 lb a.i./A) , and minimum incorporation depth 18 

### ( i.e. , 0.5 inch) to calculate EECs.

TerrPlant estimates potential exposure from a single application using de fault assumptions for runoff ( fraction of 0.05 gi ven the solubility is > 100 ppm) ( Table 1 1 )

. Because effects due to spray drift are not expected with seed treatment uses, the spray drift fraction was defined to equal zero ( i.e. , also the default for granular applications) in the model; in addition, the

18 Mayberry, K.S. 2000. U.C. Cooperative Extension Sample Cost to Establish and Produce Sugar Beets. http://coststudies.ucdavis.edu/files/sugarbeets.pdf

### vegetative vigor study is not used for RQ calculation . Instead, this analysis only uses the seedling emerg ence study to assess exposure via runoff 19 

### . See APPENDIX B for more
information.

Table 1 1

. EECs on Plants Following Label

- Specified Seed Treatment Applications of Hymexazol Using the TerrPlant Model (lb a.i./A )

.

USE RATE (lb a.i./A) EEC from runoff to dry areas EEC from runoff to

semi

- aquatic areas Tachigaren ® 70 WP 1.25 0.125 1.25



### V. Risk Characterization

a. Risk Estimation

- Integration of Exposure and Effects Data

T oxicity data and exposure estimates are used to evaluate the potential for adverse ecological
effects on non

- target species. For this assessment of hymexazol the deterministic risk quotient method is used to provide a metric of potential risks. The RQ is a comparison of exposure estimates to toxicity endpoints; estimated exposure concentrations are divided by acute and chronic toxicity values. The resulting unitless RQs are compared to the Agency’s levels of concern (LOCs) (see Table 1 2 ), which are the Agen cy’s interpretive policy such that when LOCs are exceeded, the need for regulatory action may be considered. These criteria are used to indicate when the use of a pesticide, as directed on the label, has the potential to cause adverse effects

on non

- target organisms.

Table 1 2

. Agency Levels of Concern (LOC)

.

Risk Description RQ Taxa

Acute Potential for acute risk to non

- target organisms which may warrant regulatory action in

addition to restricted use classification acute RQ > 0.5 aquatic animals, mammals, birds

Acute Listed Species Listed species may be potentially affected by

use acute RQ > 0.05 aquatic animals

acute RQ > 0.1 mammals and
birds

Chronic Potential for chronic risk may warrant regulatory action, listed species may potentially be affected through chronic exposure chronic RQ > 1 all animals

19 “ For defining RQ values for plants exposed to runoff, measures of effect to seedling emergence are used; however, vegetative vigor could be affected by runoff (i.e. effects to plant roots). Due to limitations of testing methods, these effects are not measured and cannot be incorporated int o RQ development.” (TerrPlant v.1.2.2 User Guide, 2006)Risk Description RQ Taxa

Non

- Listed and
Listed Plant Potential for effects in non

- listed and listed plants RQ > 1 all plants



### 1. Non

- target Aquatic Animals and Plants

On an acute exposure basis, hymexazol is classified as “practically non

- toxic” to freshwater fish

and “slightly toxic” to aquatic invertebrates. With a peak surface water EEC of 13.8 μ g a.i./L, the resulting RQ values were below the LOC thresholds (acute and ES) at <0.01 for fish and

inver tebrates, respectively ( Table 1 3 ). However, this is based on a limited toxicity set with only one species of freshwater fish tested and no data for es tuarine/marine (E/M) species (fish or invertebrates). In the absence of data, the freshwater species will serve as a surrogate for E/M species, however, there is uncertainty with using freshwater values as a proxy for E/M species

, especially given that onl y one species of freshwater fish was tested

. When comparing the toxicity endpoint for freshwater fish (> 100,000 μ g/L) to the peak EEC of 13.8 μ g a.i./L, hymexazol would need to be at least over 7,200 times more toxic on an acute basis to reach the level of concern for fish (freshwater and estuarine/marine). Considering the labeled application rates and the available acute toxicity data for freshwater fish, acute ri sk is expected to be low for estuarine/marine fish.

Chronic toxicity data is available for freshwater fish and invertebrates through the EFSA (2010) risk assessment; the NOAEC for a 28

- day rainbow trout study is >100 mg/L and the NOAEC (based

on the numbe r of live juveniles) for a 21

- day Daphnia magna is 0.8 mg/L

. At these level s, the
LOC would not be exceeded ( Table 13 )

. Considering the predicted EECs (f or the maximum labeled

rate ) and the EFSA chronic toxicity data, risk i s expected to be low for expos ures to fish and
invertebrates on a chronic basis

.

There are no LOC exceedances for vascular and non

- vascular aquatic plants.

Table 1 3

. Aquatic Exposure Surface Water RQ Values for Hymexazol

Taxonomic Group Exposure Type Toxicity ( μ g/L) EEC ( μg/L ) RQ Exceeds

LOC (Y/N)

Freshwater Fish Acute LC 50 >10 0,000 13.8 <0.01 N

Chronic* NOAEC > 100,000 11.5 <0.01 N

Freshwater

Invertebrate Acute LC 50 = 30,8 00 13.8 <0.01 N

Chronic* NOAEC= 800 13.2 0.02 N

Aquatic Vascular plants Non

- listed EC 50 = 7,900 13.8 <0.01 N

Listed EC 05 =1, 100 13.8 0.01 N

Non

- listed EC 50 = 23,390 13.8 <0.01 NTaxonomic Group Exposure Type Toxicity ( μ g/L) EEC ( μg/L ) RQ Exceeds

LOC (Y/N)

Aquatic Non

Vascular Listed NOAEC = 5,790 13.8 <0.01 N

* Based on EFSA (2010) risk assessment: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/1653.pdf



### 2. Non

- Target Terrestrial Animals

For reference, the values used in the calculations for the tables below:

Standard pellet

• High application (treatment) rate = 90 g TEP / kg

- seed (138.8 fl oz TEP/cwt)

• Low application (treatment) rate = 45 g TE P/kg

- seed (69.4 fl oz TEP/cwt)

Build

- up Pellet

• High application (treatment) rate = 30 g TE P/kg

- seed (46.27 fl oz TEP/cwt) Seeding rates

• High s eeding rate = 19.8 lb seed/A

• Low seeding rate = 4.8 lb seed/A



### The acute RQs are calculated using two different equations. Equation for RQ #1 (as well as the chronic RQ calculation) does not take into account the seeding rate parameter. Instead, the Nagy dose is calculated on the basis of the daily food intake, maximum seed application rate, and animal body weight. As a result, these values demonstrably do not change across the low and high seed rate scenarios for a given application rate. On the other han d, the equation for RQ#2, which is analogous to the LD 50 

### per ft 2 

### method, does take into account seeding rates and tends to be a lower RQ estimate than RQ#1. In determining risk concern both equations should
be considered.

Mammals

Acute
The shaded cells indicate the acute LOC (0.5) exceedances and the bold indicate the additional ES LOC (0.1) exceedances.

For the Tachigaren ® 70 WP standard pellet u ses at the highest application rate (i.e., 1.25 lb a.i./A), there were acute listed and non

- listed species exceedan ces for all mammalian size classes ( Table 1 4 ). The non

- listed species RQs (i.e ., LOC ≥0.5) range from 1.74

- 3.81 and the listed species
RQs (i.e., LOC ≥0.1) from 0.13

- 3.81 for the highest application rate

. LOC exceedances are
observed down to the low end scenario as well

-- at the lowest application rate (i.e., 0.15 lb a.i./A). The Tachigaren ® 

### 70 WP build

- up pellet scenario at the lowest application rate (i.e., 0.10

lb a .i./A) and low seeding rate is similar to the low end scenario for the standard pellet use.

### Chronic The chronic RQ was calculated using the NOAEL and LOAEL to demonstrate that LOC exceedances occur at the frank effects levels (i.e., LOAEL), noting that the LOAEL (the lowest observed adverse effect level) stands for the lowest tested concentration where e ffects are observed. The RQ is based on either the NOAEL or LOAEL as marked in Table 14 . The NOAEL = 100 mg/kg

- bw/day and LOAEL = 500 mg/kg

- bw/day based on the teratogenicity study (MRID 42826307). The frank effect is reduced fetal weight (9.3% relative to the control at the highest tested dose, 500 mg/kg

- bw/day). Additional developmental delays were also observed in the study . In terms of chronic exposure, there were LOC exceedances (i.e., LOC ≥ 1.0) for all
mammalian size classes for all scenarios and at both effect levels.

Table 1 4

. Mammalian Seed Treatment RQs

-- for Tachigaren ® 70 WP as a single seed treatment application on sugar beets

.

Scenario 1 Mammalian (15 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*) High app rate / High seed rate 3.81 0.25 60.95 12.19 1.25 High app rate / Low seed rate 3.81 0.06 60.95 12.19 0.30 Low app rate / High seed rate 1.90 0.12 30.48 6.10 0.63 Low app rate / Low seed rate 1.90 0.03 30.48 6.10 0.15 High app rate (build up) / Low seed rate 1.27 0.02 20.32 4.06 0.10 Mammalian (35 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*) High app rate / High seed rate 3.25 0.13 52.07 10.41 1.25 High app rate / Low seed rate 3.25 0.03 52.07 10.41 0.30 Low app rate / High seed rate 1.63 0.07 26.03 5.21 0.63 Low app rate / Low seed rate 1.63 0.02 26.03 5.21 0.15 High app rate (build up) / Low seed rate 1.08 0.01 17.36 3.47 0.10
Mammalian (1000 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*)
High app rate / High seed rate 1.74 0.01 27.91 5.58 1.25 High app rate / Low seed rate 1.74 <0.01 27.91 5.58 0.30 Low app rate / High seed rate 0.87 0.01 13.95 2.79 0.63 Low app rate / Low seed rate 0.87 <0.01 13.95 2.79 0.15 High app rate (build up) / Low seed rate 0.58 <0.01 9.30 1.86 0.10

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)
*Bold values exceed acute listed and chronic listed and non

- listed species LOCs; highlighted cells signify values that also

exceed acute non

- listed LOCs

Acute RQ #1 = (mg a.i. /kg

- bw/day) / LD50

Acute RQ #2 = mg a.i. ft

- 2 /(LD50*bw)

Mammalian Chronic RQ = mg a.i./kg

- bw/day / adjusted NOAEL

### Birds

Acute The shaded cells indicate the acute LOC (0.5) exceedances and the bold indicate the additional ES LOC (0.1) exceedances. For the Tachigaren ® 70 WP standard pellet uses at the highest application rate (i.e., 1.25 lb a.i./A), there were acute listed and non

- listed species LOC exceedances for all avian size classes ( Table 15 ). The acute non

- listed species LOC exceedances (i.e., LOC ≥0.5) range from 0.74

- 18.08 and the listed species exceedances (i.e., LOC ≥0.1) from

0.12

- 18.08. LOC exceedances are observed down to the low end scenario as well

-- at the lowest application rate (i.e., 0.15 lb a.i./A).

Chronic
The chronic RQ was calculated using the NOAEC and LOAE C to demonstrate that LOC
exceedances occur a t the fr ank effects levels (i.e., LOAEC), noting that the LOAEC (the lowes t observed adverse effect concentration ) stands for the lowest tested concentration where
effects are observed. The RQ is based on either the NOAEC or LOAEC as marked in Table 1 5

. The NOAEC = 385 mg a.i./kg

- diet and LOAEC = 962 mg a.i./kg

- diet are based on the quail study (MRID 48716602). The frank effect is reduced eggshell thickness (5% reduction in thickness relative to the control at the highest dose level tested 962 mg a.i./ kg

- diet). No other treatment related effects were observed in this study. However, in a reproduction study for the mallard (MRID 49268101), eggshell thickness was also significantly different (8.35% effect) relative to the control in the highest dose level tested (4467 mg a.i./kg

- diet), which led to a NOAEC of 902 mg a.i./kg

- diet.

In terms of chronic exposure, there were LOC exceedances (i.e., LOC ≥ 1.0) for all avian size
classes for all scen arios and at both effect levels.

Table 1 5 . Avian Seed Treatment RQs

-- for Tachigaren ® 70 WP as a single seed treatment application on sugar beets

.

Scenario 1 Avian (20 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 18.08 0.74 164.23 65.73 1.25

High app rate / Low seed rate 18.08 0.18 164.23 65.73 0.30

Low app rate / High seed rate 9.04 0.37 82.12 32.86 0.63
Low app rate / Low seed rate 9.04 0.09 82.12 32.86 0.15

High app rate (build up) / Low seed rate 6.03 0.06 54.75 21.91 0.10

Avian (100 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 8.10 0.12 164.23 65.73 1.25

High app rate / Low seed rate 8.10 0.03 164.23 65.73 0.30Low app rate / High seed rate 4.05 0.06 82.12 32.86 0.63
Low app rate / Low seed rate 4.05 0.01 82.12 32.86 0.15

High app rate (build up) / Low seed rate 2.70 0.01 54.75 21.91 0.10

Avian (1000 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 2.57 0.01 164.23 65.73 1.25

High app rate / Low seed rate 2.57 <0.01 164.23 65.73 0.30

Low app rate / High seed rate 1.28 <0.01 82.12 32.86 0.63

Low app rate / Low seed rate 1.28 <0.01 82.12 32.86 0.15

High app rate (build up) / Low seed rate 0.86 <0.01 54.75 21.91 0.10

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

*Bold values exceed acute listed and chronic listed and non

- listed species LOCs; highlighted cells signify values that
also exceed acute non

- listed LOCs

Acute RQ #1 = (mg a.i. /kg

- bw/day) / LD50

Acute RQ #2 = mg a.i. ft

- 2 /(LD50*bw)

Avian Chronic RQ = mg kg

- 1 seed / NOAEL



### 3. Terrestrial Invertebrates

EPA reviewed data and EFS A (2010) risk assessment report acute oral and contact honey bee
toxicity as LD 50 

### > 100 μ g /bee and LC 50 

### > 100 μ g/ bee, respectively, for the hymexazol technical.

4. Non

- target Terrestrial Plants The risk to plants was assessed using TerrPlant v. 1.2.2 ( Appendix B ) using calculations of runoff only EECs as described previously and seedling emergence data: onion (monocot) IC 25 

### = 174 lb a.i./A and NOAEC = 152 lb a.i./A; and, cabbage (dicot) IC 25 

### = 35 lb a.i./A and NOAEC = 16 lb a.i./A

. From the Terr P lant a nalysis, there were no LOC exceedances for applications at the 1.25 lb a.i./A

rate ( Table 1 6 ).

T able 1 6

. Screening Level Analys is

- Terr Plant RQs for runoff only in dry and semi

- aquatic areas

Plant Type Rate lb a.i./A

1.25

Monocot <0.1
Monocot (listed) <0.1

Dicot <0.1
Dicot (listed) <0.1

### b. Risk Description and Characterization

Risks to Aquatic Organisms

Animals

On an acute and chronic exposure base s, t he risk to freshwater fish and invertebrates is
considered low. Data are not available for estuarine/marine (E/M) species (fish or invertebrates). In the absence of data, the freshwater species may serve as a surrogate for E/M species, thus, the acute risk is anticipated to be low

. Chronic toxicity data for freshwater fish and inve rtebrates is available through the EFSA (2010) risk assessment.

Plants All of the RQs for aquatic vascular and non

- vascular plants are below the LOCs for risk to listed

and non

- listed species. Therefore, likelihood of direct risk to aquatic plants from t he use of hymexazol is considered low.

Risks to Terrestrial Organisms

Terrestrial invertebrates

H ymexazol is a registered systemic fungicide applied to sugar beets, a pollinator attractive crop. The EPA study review and EFSA (2010) risk assessment reporting acute oral and contact honey bee toxicity as LD 50 

### > 100 μ g /bee and LC 50 

### > 100 μ g/ bee, respectively, for the hymexazol technical, suggests that the risk to honey bees on an acute oral and contact basis is expected to be low. In addition, the metabolism in sugar beets study (MRID 42826314) finds substantial evidence that hymexazol rapidly metabolizes (degrades) to CO 2 

### in the plant and subsequently gets incorporated into sugars. This suggests that by the time this biennial crop blooms

– i.e., in the second year of growth

-- it is expected that the degradation pathway of hymexazol inside the plant is not likely to lead to exposure to adults or younger life stages in the hive

.

Terrestrial Plants In the screening level analysis with TerrPlant, the re were no LOC exceedances for applications at the 1.25 lb a.i./A rate. Only the seedling emergence data were used for RQ calculations because these data are more representative of effects resulting from runoff. Vegetative vigor data are representative of effects resulting from spray drift. Given that spray drift is not an expected exposure route, vegetative vigor results and the spray drift analysis were not included. These results are consistent with a lack of incidents reported for terrestrial plants. A s a result, effects are not expected to terrestrial plants.

Terrestrial Vertebrates

M odifications to application rate (in terms of lb a.i./A) may substantially reduce risk to mammals
and birds

. Critical information on the label and usage reports that contribute to changing the application rate includes seed treatment application rate (i.e. gram of TEP/kg seed) and seeding rate (i.e., lb seed/A).

### With respect to the outputs in T

- REX, if seeding rates are changed, the risk quotie nts change for
the acute RQ (#2) for birds and mammals. This is on account of the types of equations used in
the T

- R EX model; RQ (#2) equations account for risk on the basis of the amount of pesticide
present per square foot and needed to reach the LD 50 

### . However, when the application rates are
redu ced, the risk quotients decrease for all risk categories: acute (#1 and #2) as well as the chronic (NOAEL

- based and LOAEL

- based).

Given this limitation on the seeding rates pa rameter in T

- REX additional calculations were developed

– i.e., the seed consumption approach (SCA)

-- that confirm the T

- REX based risk conclusions but highlight the importance of accurate seeding rate assumptions. Appendix D provides a logical outline of the calculations used for the development of the SCA using the lowest and highest application rates (40 and 90 g TEP/kg

- seed) for the standard pellet, the highest application rate (30 g TEP/kg

- seed) for the build

- up pellet, and the lowest and highest seedi ng rates (4.8 and 19.8 lb seed/Acre) from those listed in T

- REX . For clarity, the SCA approach is presented in the risk characterization section for the highest rates scenario. However, Appendix

E outlines all refinements of the RQ estimates including those calculated in T

- REX and the SCA for combinations (or ‘scenarios’) of application rates ( standard pellet high: 90 g TEP/kg

- seed and low:

45 g TEP/kg

- seed ; build up pellet high: 30 g TEP/kg

- seed ) and seeding rates (high: 19.8 lb seed/A; and low: 4.8 lb seed/A). Conclusions of the T

- REX modeling only are presented throughout the body of this document. For details on the SCA refinements and real

- world case study examples
with the wood mouse and zebra finch, see Appendix E

.

Mammals

Hymexazol is classified as “slightly toxic” to mammals on an acute oral basis, however, becau se of the high seed treatment application rate (1.25 lb a.i./A) , the expected residues on the treated seeds, should direct consum ption occur, are high ( maximum seed application rate: 63,230 mg a.i./kg

- seed ; amount of available a.i.: 13.1 mg a.i./ft 2 

### ) as are the calculated doses received by the three size classes (a range of 2,147

- 13,397 mg a.i./kg

- bw/day) , thus leading to acute and chronic

LOC exceedances for all mammalian size classes

.

If the seeding rate from above (19.8 lbs a.i./A) is changed to 4.8 lbs a.i./A, if the seeding rate remains 19.8 lbs a.i./A but the application (treatment) rate is halved (from 138.8 fl oz /cwt to 69.4 fl oz/cwt), or if a seeding rate of 4.8 lbs a.i./A and application (treatment) rate of 69.4 fl oz/cwt is used, the risk quotients decrease but risk co nclusions do not change for mammals

.

Thus, a combination of seeding rate and application (t reatment) rate reduction may substantially
reduce risk , as suggested by results of the build

- up pellet scenario

. G iven that the label does not specify a maximum application rate per acre

– i.e., it only indicates the weight of end use product per weight of seed

– means that there is uncertainty in the above estimates.

In an effort to refine the T

- REX output, EFED calculated the amount of seeds a mammal would
need to consume to reach the acute ri sk, acute endangered species risk, and chronic risk LOC
levels. Table 1 7 through Table 1 9 provide the following refinements: the number of sugar beet

### seed pellets that a 15, 35, and 1000g mammal would need to consume at the highest application

rate , the percentage of the daily dietary intake of that size class, and the area the organism would need to forage in order to attain the LOC. Consuming more seeds than reported in the tables would yield an LOC exceedance for that risk category. The following assumptions were made: the highest seeding rate available in T

- REX was used (i.e., 19.8 lb seeds/acre), that the mammals assessed are granivores, and, as a result, the mass fraction of water in the food items is 0.1 (T

REX User Guide)

– i.e. relevant for determination of the daily mass food intake. A detailed
desc ription of the calculations

-- including the low application (treatment) rate and low seeding

rate

-- can be found in Appendix D

. The multiple scenario outputs and real

- world case study example wi th the wood mouse are presented in Appendix E

.

Based on the acute exposure below, the foraging areas covered to result in consuming sufficient seed to reach a level of concern by all size classes seem reasonable and very likely. Specifically,
the small a nd middle size class mammals cover less ground and need to consume a smaller percentage of their daily mass intake to reach the acute LOC and much less so to reach the acute endangered mammal LOC than do the larger size class mammals. The number of seeds c onsumed required to reach the chronic LOC is lower than that required for reaching either acute level of concern. The risk to larger mammals increases with respect to chronic exposure as they would
need to cover less ground and consume less than they would for acute exposure to show effects.

Chronic exposure is based on a teratogen icit y study (MRID 42826307) that showed reduced mean feta l weight (9.3% below control) at the highest tested concentration ( also LOAEL: 500 mg a.i./kg

bw), a dose which was not maternally toxic. As a result, the developmental NOAEL for the study is 100 mg a.i./kg

- bw. Additional developmental delays were also observed in the study. Though

a 2

- generation reproduction study (MRID 42826309) suggests no treatment relate d effects on the general physical condition, body weight, or developmental landmarks of the F 1 

### and F 2 

### pups, post

- implantation s urvival rate and litter size were significantly reduced in the high dose ( also

LOAEL: 159 mg a.i./kg

- bw) F 1 

### (↓17%) and F 2 

### (↓20%) offspring compared to controls. Lower survival rates led to reduced litter size at birth/on postnatal day (PND) 1 in both the F 1 

### (↓26

- 27%) and F 2 

### (↓17%) generations. This reduction continued until PND 4 (pre

- cull), with 16% fewer

F 1 

### pups and 19% fewer F 2 

### pups per litter compared to controls. It was impossible to determine if
this was a maternal or in utero effect without more data; therefore, it was attributed to both. The paternal and offspring NOAEL in the 2

- generation study is 31 mg a.i./kg

- bw and furt her supports the risk conclusions based on the development/teratogenicity study. Furthermore, the developmental NOAEL (100 mg/kg/day) is protective of the reproductive effects at 159 mg/kg/day in the 2

- generation study

. If this laboratory

- observed effect o ccurs in the environment, it could , in return, have effects on reproduction, survival, and growth of individuals and subsequent effects on a given mammalian population.

The refinements presented below (high application rate for the standard pellet use and high seeding rate) further support the acute and chronic risk conclusions calculated from T

- REX; that
is, there is potential risk of mortality and reproductive effects to mammals resulting from acute and chronic exposures. In other words , the fraction of pellets consumed and required to reach the LOC is in many cases much lower than 100% and the area required to collect as many pellets

### is not unre a sonab le

. However, these refinements further emphasize the importance of accurate seeding rate assumptions in r isk cal culations for seed applications; see Appendix E for a comprehensive analysis of alternative application scenarios

. High seeding rates, for example, imply a reduced foraging area required to consume the amount of seed needed to reach a given

LOC. The greatest risk concern is evidenced by hig h application and seeding rates; in particular, in the standard pellet case. The build

- up pellet application rate is lower and presents a possibility
of concern on a chronic basis particularly for small and mid

- siz e mammals ( Appendix E ).

Table 17 . Acute Risk to Mammals: Comparisons to non

- listed species LOC for mammals foraging on hymexazol treated seed.

Size (g) 0.5 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to
reach 0.5 adj LD 50 (mg a.i.) Mass of pellet to
reach 0.5 adj. LD 50 (mg

pellet) # Pellets
consumed to
reach 0.5 adj. LD 50 Daily
mass of
food

intake (mg) Fraction of Daily
mass intake to
reach 0.5 adj.

LD 50 (%)* Area covered (ft 2 )**

15 1,758 26 1,256 42 3,178 39.5 2.02

35 1,423 50 2,371 79 5,125 46.3 3.82

1000 615 615 29,301 977 33,951 86.3 47.2

The LD 50 = 1600 mg a.i./kg

- bw for a 350g rat. The adjusted LD 50 = 3,517 mg a.i./kg

- bw for a 15g mammal, 2,845 mg a.i./kg

- bw for a 35g mammal, and 1231 mg a.i./kg

- bw for a 1000g mammal *(Mass of pellet to reach 0.5 adjusted LD 50 / Daily mass intake) x 100 **Number of pellets consumed to reach the 0.5 adjusted LD 50 / 20.7 seed pellets ft

- 2 (See Appendix D for details)



### Table 18 . Acute Endangered Mammal Species Risk: Comparisons to listed species LOC for threatened and endangered mammals consuming hymexazol treated seed.

Size (g) 0.1 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to

reach 0.1 adj LD 50 (mg a.i.) Mass of pellet to

reach 0.1 adj. LD 50 (mg

pellet) # Pellets
consumed to

reach 0. 1 adj. LD 50 Daily
mass of

food
intake (mg) Fraction of Daily
mass intake to

reach 0.1 adj.

LD 50 (%)* Area covered (ft 2 )**

15 352 5.3 251 8 3,178 7.9 0.40

35 285 10 474 16 5,125 9.3 0.76

1000 123 123 5,860 195 33,951 17.3 9.44

The LD 50 = 1600 mg a.i./kg

- bw for a 350g rat. The adjusted LD 50 = 3,517 mg a.i./kg

- bw for a 15g mammal, 2,845 mg a.i./kg

- bw for a 35g mammal, and 1231 mg a.i./kg

- bw for a 1000g mammal *(Mass of pellet to reach 0.1 adjusted LD 50 / Daily mass intake) x 100
**Number of pellets consumed to reach the 0.1 adjusted LD 50 / 20.7 seed pellets ft

- 2 (See Appendix D for details)

### Table 19 . Chronic Risk to Mammals: Comparisons to chronic LOC for mammals consuming hymexazol treated seed.

Size (g) Adjusted

NOAEL (mg a.i./kg

bw) Mass of

a.i. to reach adj

NOAEL (mg a.i.) Mass of pellet to
reach adj.

NOAEL (mg

pellet) # Pellets
consumed to reach adj.

NOAEL Daily
mass of
food

intake (mg) Fraction of Daily
mass intake to reach adj. NOAEL (%)* † Area covered (ft 2 )**

15 220 3.3 157 5 3,178 4.9 0.25

35 178 6.2 296 10 5,125 5.8 0.48

1000 77 76.9 3,662 122 33,951 10.8 5.90

The NOAEL = 10 0 mg a.i./kg

- bw for a 350g rat (based on teratogenicity study , MRID 42826307 ) *(Mass of pellet to reach adjusted NOAEL / Daily mass intake) x 100 **Number of pellets consumed to reach the adjusted NOAEL / 20.7 seed pellets ft

- 2 (See Appendix D for details)
†See Appendix E for calculations based on the LOAEL.



### Birds Hymexazol is classified as “slightly toxic” to birds on an acute oral basis and “practically non

toxic” to birds on an acute dietary basis, however, because of the high seed treatment application rate (1.25 lb a.i./A), the expected residues on the treated seeds, sh ould direct consumption occur, are high (maximum seed application rate: 63,230 mg a.i./kg

- seed; amount of available a.i.: 13.1 mg a.i./ft 2 

### ) as are the calculated doses received by the three size classes (a range of 4,086

- 16,003 mg a.i./kg

- bw/day), thus lea ding to acute and chronic LOC exceedances for all avian size classes.

As for the mammals, if the seeding rate from above (19.8 lbs a.i./A) is changed to 4.8 lbs a.i./A, if the seeding rate remains 19.8 lbs a.i./A but the application (treatment) rate is halved (from 138.8 fl oz/cwt to 69.4 fl oz/cwt), or if a seeding rate of 4.8 lbs a.i./A and application (treatment) rate of 69.4 fl oz/cwt is used, the risk quotients decrease but risk conclusions do not change for the

birds

.

Thus, a combinatio n of seeding rate and application (treatment) rate reduction may substantially
reduce risk. G iven that the label does not specify a maximum application rate per acre

– i.e., it only indicates the weight of end use product per weight of seed

– means that th ere is uncertainty
in the above estimates.

Once again in an effort to refine the T

- REX output, EFED calculated the amount of seeds a bird would need to consume to reach the acute risk, acute endangered species risk, and chronic risk
LOC levels. Table 20 t hrough Table 22 provide the following refinements: the number of sugar beet seed pellets that a 20, 100, and 1000g bird would need to consume at the highest application

rate , the percentage of the daily dietary intake of that size class, and the area the organism would need to forage in order to attain the LOC. Consuming more seeds than reported in the tables would yield an LOC exceedance for that risk category. The following assumptions were made: the highest seeding rate available in T

- REX was used (i.e., 19.8 lb seeds/acre), that the birds assessed are granivores, and, as a result, the mass fraction of water in the food items is 0.1

– i.e. relevant

### for determination of the daily mass food intake. A detailed description of the calculations

-- including the low application (treatment) rate and low seeding rate

-- can be found in Appendix

D . The multiple scenario outputs and real

- world case study example with the zebra finch ar e presented in Appendix E

.

Based on the acute exposure below, the foraging areas covered to result in consuming sufficient
seed to reach a level of concern by all size classes seem reasonable and very likely. Specifically,
the small and middle size class birds cover less ground and need to consume a smaller percentage of their daily mass intake to reach the acute LOC and much less so to reach the acute endangered bird LOC than do the larger size class birds. Generally, t he number of seeds consumed and

re quired to reach the chronic LOC is lower than that required for reaching either acute level of concern. The risk to larger bird s increases with respect to chronic exposure as they would need to cover less ground and consume less than they would for acute e xposure to show effects.

T he chronic endpoint used in this assessment from the avian reproduction study for the quail (MRID 48716602) is based on egg shell thickness (5% reduction relative to the control at the highest dose level tested, 962 mg a.i./kg

- di et, which led to a NOAEC of 385 mg a.i./kg

- diet)

. Though statistical difference in egg shell thickness was detected it is possible that this difference is not biologically significant given that the mean egg shell difference at the highest level tested (1 000 mg/kg

- diet) is 0.219 ± 0.014 mm, comparable to (according to the study author’s) the historical control value of 0.219 ± 0.010 mm. The control mean for egg shell thickness for the study, however, is 0.231 ± 0.015 mm. No other treatment related effects were observed in this study. However, in a reproduction study for the mallard (MRID 49268101), eggshell thickness was also significantly different (8.35% effect) relative to the control in the highest dose level tested (4467 mg a.i./kg

- diet), which led to a NOAEC of 902 mg a.i./kg

- diet.

The refinements presented below (high application rate for the standard pellet use and high seeding rate) further support the acute and chronic risk conclusions calculated from T

- REX; that
is, there is potential risk of mortality and reproductive effects to birds resulting from acute and chronic exposures

. In other words, the fraction of pellets consumed and required to reach the LOC is in many cases much lower than 100% and the area required to collect as many pellet s is
not unreasonable. However, these refinements further emphasize the importance of accurate seeding rate assumptions in risk calculations for seed applications , see Appendix E for a comprehensive analysis of alternative application scenarios

. High seed ing rates, for example, imply a reduced foraging area required to consume the amount of seed needed to reach a given LOC. The greatest risk concern is evidenced by high application and seeding rates; in particular, in the standard pellet case. The build

- up pellet application rate is lower but presents a possibility
of concern on a chronic basis for all size classes ( Appendix E ).

### Table 20 . Acute Risk to Birds: Comparisons to 0.5 Adj. LD 50

Size (g) 0.5 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to

reach 0.5 adj LD 50 (mg a.i.) Mass of pellet to

reach 0.5 adj. LD 50 (mg

- pellet) # Pellets
consumed

to reach 0.5 adj. LD 50 Daily mass
of food intake (mg) Fraction of Daily mass

intake to
reach 0.5 adj. LD 50 (%)* Area covered (ft 2 )**

20 443 8.9 422 14 5,062 8.3 0.68

100 564 56 2,683 89 14,432 19 4.32

1000 796 796 37,904 1,263 64,615 59 61.04

The LD 50 = 827 mg a.i./kg

- bw for a 12.7 g passerine. The adjusted LD 50 = 885 mg a.i./kg

- bw for a 20g bird, 1,127 mg a.i./kg

- bw for a 100g bird, and 1,592 mg a.i./kg

- bw for a 1000g bird *(Mass of pellet to reach 0.5 adjusted LD 50 / Daily mass intake) x 100 **Number of pellets consumed to reach the 0.5 adjusted LD 50 / 20.7 seed pellets ft

- 2 (See Appendix D for details)



### Table 21

. Acute Endangered Bird Species Risk: Comparisons to 0.1 Adj. LD 50

Size (g) 0.1 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to

reach 0.1 adj LD 50 (mg a.i.) Mass of pellet to

reach 0.1 adj. LD 50 (mg

pellet) # Pellets
consumed to

reach 0.1 adj. LD 50 Dail y mass of food

intake (mg) Fraction of Daily mass

intake to reach 0.1 adj.

LD 50 (%)* Area covered (ft 2 )**

20 88.5 1.8 84 3 5,062 1.7 0.14

100 113 11 537 18 14,432 3.7 0.86

1000 159 159 7,581 253 64,615 12 12.21

The LD 50 = 827 mg a.i./kg

- bw for a 12.7 g passerine. The adjusted LD 50 = 885 mg a.i./kg

- bw for a 20g bird, 1,127 mg a.i./kg

- bw for a 100g bird, and 1,592 mg a.i./kg

- bw for a 1000g bird *(Mass of pellet to reach 0.1 adjusted LD 50 / Daily mass intake) x 100 **Number of pellets consumed to reach the 0.1 adjusted LD 50 / 20.7 seed pellets ft

- 2 (See Appendix D for details)



### Table 22 . Chronic Risk to Birds : Comparisons to chronic LOC for birds consuming hymexazol
treated seed.

Size (g) Adjusted

NOAEC (mg a.i./kg

diet ) Mass of

a.i. to reach adj

NOAEC (mg a.i.) Ma ss of pellet to
reach adj.

NOAEC (mg

pellet) # Pell ets
consumed to reach adj.

NOAEC Daily
mass of
food

intake (mg) Fraction of Daily
mass intake to reach adj.

NOAEC (%)* † Area covered (ft 2 )**

20 385 1.95 92.8 3 5,062 1.8 0.15

100 5.56 265 9 14,432 1.8 0.43

1000 24.9 1,185 39 64,615 1.8 1.91

The NOAEC = 385 mg a.i./kg

- diet (based on bobwhite quail study MRID 48716602 ) *(Mass o f pellet to reach NOAEC / Daily mass intake) x 100 **Number of pellets consumed to reach NOAEC / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)
†See Appendix E for calculations based on the LOAEC

.

### Review of Incident Data

Reviews of the Ecological Incident Information System (EIIS) v.2.1.1

, OPPs Incident Data System (IDS) , and the Avian Incident Monitoring System (AIMS) 20 

### were conducted on 2/11/15. There are no reported incidents for hymexazol in the EIIS, IDS or AIMS databases.

Federally Threatened and Endangered (Listed) Species Concerns

Before completing this Registration Review, the Agency will conduct an ecological risk assessment to address the Agency’s obligations under both the Endangered Species Act (ESA)
and FIFRA. While the risk assessment supporting this proposed interi m Registration Review decision evaluates risks to species that are not subject to the ESA, EPA is still in the process of conducting a risk assessment for endangered and threatened (listed) species and their designated critical habitats for hymexazol

. T her efore, EPA has not completed effects determinations for listed species associated with the registered uses of hymexazol

.

At this time, EPA has not fully developed its risk assessment process for listed species

. In November 2013, the EPA, along with the U .S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services) , and the U.S. Department of Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks to listed species from pe sticides. The Interim Approaches were developed jointly by the Agencies in response to the National Academy of Sciences’ (NAS) recommendations and reflect a common approach to risk assessment shared by the Agencies as a way of addressing scientific differences
betwe en the EPA and the Services. The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344 , outlines recommendations on specific
scientific and technical issues related to the de velopment of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. The joint Interim Approaches were released prior to a stakeholder workshop held on November 15,

2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and State

- FIFRA Issues Research and Evaluation Group ( SFIREG) meetings, allowing additional opportunities for stakeholders to comment on the

Int erim Approaches. As part of a phased, iterative process for developing the Interim Approaches, the Agencies will also consider public comments on the Interim Approaches in connection with the development of upcoming Registration Review decisions. The deta ils of the joint Interim Approaches are contained in the white paper “Interim Approaches for National

Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report,” dated November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html

.

20 http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm

### Clean Water Act

Hymexazol is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

. 

### In addition, no Total Maximum Daily Loads (TMDL) have been developed for hymexazol , based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_polluta

nt_group_name=PESTICIDES



### . More information on impaired water bodies and TMDLs can be found

at http://www.epa.gov/owow/tmdl/

.



### Endocrine Disruptor Screening Program

Hymexazol was not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing. For additional information on the EDSP, visit http://www.epa.gov/endo/

.

References

Doran PM. 1997. Hairy Roots: Culture and Applications. Harwood Academic Publishers, Amsterdam, The Netherlands.

European Food Safety Authority. 2010. Conclusion of Pesticide Peer Review: Conclusion on the peer review of the pesticide risk assessment of the active substance hymexazol. Parma, Italy. November 4, 2010. http://www.efsa.europa.eu/en/scdocs/doc/1653.pdf

Harvesion RM, Windels CE, Smith JA, Brantner JR, Cattanach AW, Giles JF, Hubbell L, Cattanach NR. 2007. Fungicide registration and a small niche marke t: A case history of hymexazol seed treatment and the U.S. sugar beet industry. Plant Disease 91:780

- 790.

Mueller DS, Bradley CA. 2015. Field Crop Fungicides for the North Central United States. Iowa State University. University of Illinois. Accessed Marc h 2015 at https://www.ncipmc.org/resources/Fungicide%20Manual4.pdf

.

Payne, PA, Williams, GE. 1990. Hymexazol treatment of sugar

- beet seed to control seedling disease caused by Pythium spp. and Aphanomyces cochlioides . Crop Protection. 9:371

- 377.

U.S. EPA. 1995a. Request to Review the New Chemical Tachigaren Technical (Hymexazol) for Use as a Seed Treatment (Chemical No. 129107). Office of Prevention, Pesticides, and

Toxic Subst ances. Office of Pesticide Programs. Washington, DC. April 4, 1995. DP

Barcode: 209885.

### U.S. EPA. 1995b. New chemical registration of the fungicide hymexazol: Transmittal of Administrative Conclusions, Environmental Fate Assessment and Results of Study

Re views. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, DC. April 28, 1995. DP Barcodes: 209851, 205149.

U.S. EPA. 2010a. Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecologi cal Risk, Endangered Species, and Drinking Water Exposure Assessments for Hymexazol. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, DC. March 4, 2010. DP Barcode: 371500.

U.S. EPA. 2010b. EFED Response: R ebuttal to EPA’s Classification of Ecotoxicity Studies for Hymexazol (MRIDs 43926302, 43926301, 44071301

- 44071310, 44071311

- 44071320). Office of Chemical Safety and Pollution Prevention. Office of Pesticide Programs. Washington, DC. December 7, 2010. DP Ba rcode: 384399.

Ypema H. 2003. Fungicides, Hymexazol. Encyclopedia of Agrochemicals. Accessed March 2015

at http://onlinelibrary.wiley.com/doi/10.1002/047126363X.agr110/a bstract

.

### Appendix A . TREX Model Sample Input (Note: Outputs are available in the body of the document)

INPUT Table 1. Input

- Sugar Beet Seed Treatment (1.25 lb a.i./A)

Chemical Name: Hymexazol Application Rate (lb ai/acre)

Seed Treatment? (Check if yes) TRUE Seeding Rate (lbs/acre)

Use: 135 19.8
Product name and form: Tachigaren 70 WP % A.I. (leading zero must be entered for
formulations <1% a.i.): 70.00% Application rate (fl oz/cwt) 

### 138.8

Half

- life (days): 

### 35 Application Interval (days):
Number of Applications: 

### 1 Are you assessing applications with

variable rates or intervals? 

### no



## Avian

Endpoint Toxicity value Indicate test species below Optional Test Organism Body weight (g) Optional Test Species Name

LD50 (mg/kg

- bw) 

### 827.00 3 12.70 Zebra
finch LC50 (mg/kg

diet) 

### 5200.00 1 NOAEL (mg/kg

bw) 1 NOAEC (mg/kg

diet) 

### 385.00 1

Enter the Mineau et al. Scaling Factor 

### 1.15

## Mammalian

Acute Study Chronic Study 

### Size (g) of mammal used in toxicity study Default rat body weight is 350 grams 350 350

Endpoint Toxicity value Reference (MRID)
LD50 (mg/kg

- bw) 

### 1600.00 LC50 (mg/kg

diet) Reported

Chronic Endpoint 

### 100.00

1 Is dietary concentration

(mg/kg

- diet) reported from the available chronic

mammal study? (yes or no) 

### no

Enter dietary concentration

(mg/kg

- diet)

Estimated Chronic Diet Concentration Equivalent to Reported Chronic Daily Dose 

### 2000 mg/kg

- diet based on standard FDA
lab rat conversion



### Anima l Size Crop Maxim

um Applic ation
Rate Maximu m Seed Applicati
on Rate Avian Nagy
Dose Mammalia n Nagy

Dose Availa
ble AI

(lbs ai/A) (mg ai/kg seed) (mg ai/kg

bw/day) (mg ai/kg

bw/day) (mg ai ft

- 2)
Small sugar beet for seed production 1.25 63229.91 16002.78 13396.64

13.06 Mediu

m 9125.47 9258.87 Large 4085.59 2146.70

### Appendix B . Terr Plant Model Input/output

Table 1. Chemical Identity.

Chemical Name Hymexazol
PC code 129701

Use sugar beets Application Method seed treatment

Application Form wettable powder Solubility in Water (ppm) 65,100
Table 2. Input parameters used to derive EECs.

Input Parameter Symbol Value Units
Application Rate A 1.25 lb a.i./A

Incorporation I 0.5 none Runoff Fraction R 0.05 none

Drift Fraction D 0 none

Table 3. EECs for Hymexazol. Units in lb a.i./A.

Description Equation EEC
Runoff to dry areas (A/I)*R 0.125
Runoff to semi

- aquatic areas (A/I)*R*10 1.25 Spray drift A*D 0 Total for dry areas ((A/I)*R)+(A*D) 0.125

Total for semi

- aquatic areas ((A/I)*R*10)+(A*D) 1.25

Table 4. Plant survival and growth data used for RQ derivation. Units are in lb a.i./A.
Seedling Emergence Vegetative Vigor Plant type EC 25 NOAEC EC 25 NOAEC

Monocot 174 152 x x

Dicot 35 16 x x

Table 5. RQ values for plants in dry and semi

- aquatic areas exposed to Hymexazol through runoff and/or spray drift.*

Plant Type Listed Status Dry Semi

- Aquatic Spray Drift

Monocot non

- listed <0.1 <0.1 <0.1

Monocot listed <0.1 <0.1 <0.1

Dicot non

- listed <0.1 <0.1 <0.1

Dicot listed <0.1 <0.1 <0.1
*If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group.

### Appendix C

. Example of SWCC Aquatic Exposure

Summary of Water Modeling of Hymexazol and the USEPA Standard Pond



### Estimated Environmental Concentrations for Hymexazol are presented in Table 1 for the USEPA standard pond with the MNsugarbeetSTD field scenario. A graphical presentation of the year

- to

year peaks is presented in Figure 1. These values were generated with the Surface Water Concentration Calculator (SWCC Version 1.106). Critical input values for the model are

summarized in Tables 2 a nd 3.

This model estimates that about 0.65% of Hymexazol applied to the field eventually reaches the water body. The main mechanism of transport from the field to the water body is by runoff (99.1% of the total transport) followed by erosion (0.87%).

In the water body, pesticide dissipates with an effective water column half

- life of 128.5 days. (This value does not include dissipation by transport to the benthic region; it includes only processes that result in removal of pesticide from the complete syste m.) The main source of dissipation in the water column is metabolism (effective average half

- life = 128.8 days) followed by volatilization (59224 days).

In the benthic region, pesticide dissipates relatively quickly (2.5 days). The main source of dissipat ion in the benthic region is metabolism (effective average half

- life = 2.5 days). Most of the pesticide in the benthic region (87%) is sorbed to sediment rather than in the pore water.

Table 1. Estimated Environmental Concentrations (ppb) for Hymexazol.

Peak (1

- in

- 10 yr) 6.99

4

- day Avg (1

- in

- 10 yr) 6.91

21

- day Avg (1

- in

- 10 yr) 6.67

60

- day Avg (1

- in

- 10 yr) 5.81

365

- day Avg (1

- in

- 10 yr) 1.90

Entire Simulation Mean 0.711

Table 2. Summary of Model Inputs for Hymexazol.

Scenario MNsugarbeetSTD

Cropped Area Fraction 1

Koc (ml/g) 59.6

Water Half

- Life (days) @ 25 °C 46.2

Benthic Half

- Life (days) @ 0 °C 5.16

Photolysis Half

- Life (days) @ 40 °Lat 0

Hydrolysis Half

- Life (days) 0Soil Half

- Life (days) @ 25 °C 23.1

Foliar Half

- Life (days) 0

Molecular Wt 99.09

Vapor Pressure (torr) 1.37e

- 3

Solubility (mg/l) 65100

Table 3. Application Schedule for Hymexazol.

Date (Days Since Emergence) Type Amount (kg/ha) Eff. Drift

- 7 Incorporated to 2

cm 0.71 1.0 0.0

Figure 1. Yearly Peak Concentrations

### Appendix D. Characterization Calculations for Avian and Mammalian Exposure to Treated Sugar Beet
Seeds

Calculations applicable for acute exposure to a 20g bird. The values marked in italics would need to change for other size classes; the values in bold stay constant for each size class

– however, these values can change if assumptions change (e.g. seeding rate) or the label specifications change (e.g. application rate).
Similar calculations apply for chronic risk to birds and for acute/chronic risk to mammals. Note that t he ‘adjustment’ to the endpoints refers to the body weight adjustment to the three size classes of birds and
mammals ; this adjustment is not conducted for chronic bird endpo ints because no data exist to incorporate scaling factors ( see T

- REX User Guide).

Assuming birds eat seed pellets, how many seed pellets would it need to eat to reach LD 50 

### , how does this compare to its daily feeding rate, and how much ground area (on fiel d) would the bird need to forage to consume that many seeds ?

I. Baseline Calculations

1. What is the weight of raw seed and seed pellet? Given (from label):

• 100,000 seeds = 1 kg of raw sugar beet seed

o 1 seed weight = 1 kg /100,000 seed x 1,000,000 mg/1 kg = 10 mg

Standard pellet

• 2:1 weight ratio of pelleting mixture to raw seed

o 1 seed pellet weight = 10 mg x 3 = 30 mg

Build

- up pellet

• 3:10 weight ratio of pelleting mixture to raw seed

o 1 seed pellet weight = 10 mg x 13 = 130 mg

2. How much pesticide is in a seed pellet?

Given (from label): Standard pellet

• 45

- 90 grams of TEP (70% a.i.) per unit of 100,000 seeds

• 45,000

- 90,000 mg of TEP (70% a.i.) per 1 kg of raw seed High application rate

o 90,000 mg (0.70) / kg = 63,000 mg a.i./kg

- seed

o 63,000 mg a.i./kg

- seed x 1 kg

- seed/3kg

- pellet = 21,000 mg a.i./kg

- pellet Low application rate

o 45,000 mg (0.70)/kg = 31,500 mg a.i./kg

- seed

o 31,500 mg a.i./kg

- seed x 1 kg

- seed/3kg

- pellet = 10,500 mg a.i./kg

- pellet

Build

- up pellet

• 20

- 30 grams of TEP (70% a.i.) per unit of 100,000 seeds

• 20,000

- 30,000 mg of TEP (70% a.i.) per 1 kg of raw seed

### High application rate

o 30,000 mg (0.70) / kg = 21,000 mg a.i./kg

- seed

o 21,000 mg a.i./kg

- seed x 1 kg

- seed/13kg

- pellet = 1,615 mg a.i./kg

- pellet Low application rate

o 20,000 mg (0.70) / kg = 14,000 mg a.i./kg

- seed

o 14,000 mg a.i./kg

- seed x 1 kg

- seed/13 kg

- pellet = 1,077 mg a.i./kg

- pellet

3. How much pesticide mass is needed to reach the adjusted LD 50 

### of a 20 g bird? *See Section III below for specific case of chronic avian characterization equations.

Given (from T

- REX): Adjusted LD 50 

### = 885.30 mg a.i./kg

- bw

• 885.30 mg a.i./kg

- bw x 0.02 kg/bird = 17.7 mg a.i.

4. How much pellet mass is in the above pesticide mass ( i.e. needed to reach the adjusted LD 50 

### of a 20g bird)? Standard Pellet (max rate)

• 17.7 mg a.i. / (21,000 mg a.i./kg

- pellet) = 8.43 x 10

- 4 

### kg

- pellet

• 8.43 x 10

- 4 

### kg

- pellet x 1,000,000 mg/1 kg = 843 mg

- pellet

Build

- up Pellet (max rate)

• 17.7 mg a.i. / (1, 615 mg a.i./kg

- pellet) = 0.011 kg

- pellet

• 0.011 kg

- pellet x 1,000,000 mg/1 kg = 10,963 mg

- pellet

II. Characterization Component:

1. How many pellets constitute the above mass?

Standard Pellet (max rate; recall 30 mg is weight of one pellet )

• 843 mg

- pellet / 30 mg

- pellet = 28.1 or 28 seed pellets

Build

- up Pellet (max rate; recall 130 mg is weight of one pellet)

• 10,96 3 mg

- pellet / 130 mg

- pellet = 84.3 or 84 seed pellets

2. Based on the daily mass intake of a 20g granivore bird (i.e. 5.1 grams), what is the percent of its daily diet it would have to consume to reach the adjusted LD 50 

### ?

• 5.1 g x 1,000 mg / 1g = 5,100 mg of food consumed in a day

Standard pellet (max rate)

• 843 mg

- pellet / 5,100 mg = 0.165 or 16.5% of a 20g birds diet would have to be
consumed to reach the adjusted LD 50



### Build

- up Pellet (max rate)

• 10,960 mg

- pellet / 5,100 mg = 2.15 or 215 % of a 20g birds diet would have to be
consumed to reach the adjusted LD 50

### 3. How many seed pellets are in a squa re foot?[this value stays constant with seeding rate] High seeding rate:

Given max seeding rate for sugar beets (from T

- REX): 19.8 lb seeds/acre Knowing that 1kg = 2.2 lb, the seeding rate becomes 9 kg seeds/acre Recall: 100,000 seeds = 1 kg of raw sugar beet seed

o 100,000 seeds/ 1kg seeds x 9 kg seeds/acre = 900,000 seeds/acre Assuming that the seeding rate applies to both raw seeds and seed pellets:

o 900,000 seeds pellets/acre x 1 acre/43,560 ft 2 

### = 20.7 seed pellets/ft 2



### Low seeding rate:

Given min seeding rate for sugar beets (from T

- REX): 4.8 lb seed/acre The seeding rate becomes 2.18 kg

- seeds/acre

o 100,000 seeds/kg seeds x 2.18 kg seeds/acre = 218,182 seeds/acre

o 218,182 seed pellets/acre x 1 acre/ 43,560 ft 2 

### = 5.01 seed pellets/ft 2



### a. How much square footag e would a 20g bird need to cover to consume enough pellets to
reach the adjusted LD 50 

### ?

o Standard pellet (max rate), High seeding rate: 28 seed pellets / ( 20.7 seed pellets/ft 2 

### ) = 1.35 ft 2



### o Build

- up pellet (max rate), High seeding rate: 84 seed pellets / ( 20.7 seed pellets/ft 2 

### ) = 4.06 ft 2



### o Standard pellet (max rate), Low seeding rate: 28 seed pellets / ( 5.01 seed pellets/ft 2 

### ) = 5.6 ft 2



### o Build

- up pellet (max rate, Low seeding rate: 84 seed pellets / ( 5.01 seed pellets/ft 2 

### ) = 16.8 ft 2



### III. Particular case of chronic avian characterization equations (Standard pellet at the maximum rate and high seeding rate) . The equations are valid for LOAEC calculations as well.

Assumption: 20g bird; also a granivore Known: daily food intake = 5,062 mg Convert to kg with: 5,062 mg x (1kg/1,000,000 mg) = 5.062 x 10

- 3 

### kg or 0.0051 kg Given: NOAEC = 385 mg a.i./kg

- diet (MRID 48716602); From above sections: max pesticide in seed pellet = 21,000 mg a.i./kg

- pellet; weight of pellet = 30 mg; max seed pellets in square foot = 20.7 Note: Unlike the mammalian chronic endpoint, the avian chronic endpoint is not adjusted as no data exist for incorporating scaling factors for birds (T

- REX User Guide).

1. How much pesticide mass is needed to reach the NOAEC for a 20g bird ?

• 385 mg a.i./kg

- diet x ( 0.0051 kg diet / 20g bird ) = 1.95 mg a.i. / 20g bird

2. How much pellet mass is in the above pesticide mass ( i.e. needed to reach the NOAEC for a 20g bird)? Standard Pellet (max rate)

• ( 1.95 mg a.i./20g bird) / (21,000 mg a.i./kg

- pel let) = 9.28 x 10

- 5 

### kg

- pellet / 20g bird

• ( 9.28 x 10

- 5 

### kg

- pellet /20g bird) x 1,000,000 mg/1 kg = 92.8 mg

- pellet / 20g bird

### 3. How many pellets constitute the above mass? ( i.e. , the number of pellets at the 20 g bird dose)

• (92.8 mg

- pellet /20g bird) / 30 mg

- pellet = 3.09 pellets at the 20g bird dose

4. Based on the daily mass intake of a 20g granivore bird (i.e. 5.1 grams), what is the percent of its daily diet it would have to consume to reach the NOAEC ? ( i.e. , the percent daily diet that is the number of p ellets calculated above?)

• 5.1 g x 1,000 mg / 1g = 5,100 mg of food consumed in a day

Standard pellet (max rate)

• ( 92.8 mg

- pellet / 20g bird) / 5,100 mg = 0. 0183 or 1.83 % of a 20g birds diet would have
to be consumed to reach the NOAEC

5. How much square footage would a 20g bird need to cover to consume enough pellets to reach
the NOAEC?

• Standard pellet (max rate), High seeding rate: 3.09 pellets / ( 20.7 pellets/ft 2 

### ) = 0.15 ft 2

### Appendix E. Comparison of T

- REX and Seed Consumption Approach (SCA) Refinements

The calculations below represent a set of refinements from the maximum application rate and maximum seeding rate. Two tools were used, the T

- REX seed treatment function as we ll as a novel approach to calculation of seed consumption rates (for clarity called the ‘seed consumption approach’ or SCA). In each tool four different analyses were performed to account for the high end and low end options of the two variables of interes t: application rate and seeding rate. The application rate for the standard pellet is a range provided in the label (EPA Reg. No. 48210

- 1): 45

- 90 g TEP/kg

- seed (recall: 2:1 pelleting mixture to raw seed) . The seeding rate is also a range used in standard p ractice in T

- REX: 4.8 and 19.8 lb seed/A. To better characterize risk, a fifth analysis was also conducted on using the build

- up pellet high end rate, 30 g TEP/kg

- seed (recall: 3:10 pelleting mixture to raw seed), and the low end seeding rate in T

REX, 4.8 lb seed/A. This combination was selected on account of the instance where acute RQs

in T

- REX (for the area based RQ#2) did not exceed LOCs ( Tables E1 and E2 ).

For reference, the values used in the calculations for the tables are outlined below. Values
b efore the semicolon were used in T

- REX; values after the semi

- colon were used in SCA. For
detailed derivation of the values see Appendix D

. Standard pellet

• High application (treatment) rate = 90 g TEP / kg

- seed (138.8 fl oz TEP/cwt); 21,000 mg a.i./kg

- pellet

• Low application (treatment) rate = 45 g TEP/kg

- seed (69.4 fl oz TEP/cwt); 10,500 mg a.i./kg

- pellet

Build

- up Pellet

• High application (treatment) rate = 30 g TEP/kg

- seed (46.27 fl oz T EP/cwt); 1,615 mg a.i./kg

- pellet Seeding rates

• High seeding rate = 19.8 lb seed/A; 20.7 seed pellets/ft 2

• Low seeding rate = 4.8 lb seed/A ; 5.01 seed pellets/ft 2



### T

- REX Calculations The shaded cells indicate the acute LOC (0.5) exceedances and the bold in dicate the additional

acute ES LOC (0.1) and chronic LOC (1.0) exce edances.

The acute RQs are calculated using two different equations. Equation for RQ #1 (as well as the chronic RQ calculation) does not take into account the seeding rate parameter. Instead, the Nagy dose is calculated on the basis of the daily food intake, maximum seed application rate, and animal body weight. As a result, these values demonstrably do not change across the low and high seed rate scenarios for a given application rat e. On the other hand, the equation for
RQ#2 , which is analogous to the LD 50 

### per ft 2 

### method, does take into account seeding rates and
tends to be a lower RQ estimate than RQ#1. In determining risk concern both equations should
be considered.

The chronic en dpoint was calculated using the NOAEL/C and LOAEL/C to demonstrate that LOC exceedances occur at the frank effects levels (i.e., LOAEL/C), noting that the LOAEL (the lowest observed adverse effect level) stands for the lowest tested concentration where eff ects are
observed.

### The application rates in lbs a.i./A are calculated for reference using a combination of application rates reported in the label (in g TEP/kg

- seed) and seeding rates from T

- REX (in lb seed/A). A sample calculation for the high label repo rted application rate and high seeding rate is below:

Maximum rate (from label 21 

### ) = 90 g TEP/kg

- seed *(0.70) * = 63 g a.i./kg

- seed Conversions: 1 g = 0.001 kg; 1 kg = 2.2 lb Assumptions: 19.8 lb

- seed/A [i.e. seeding rate]

Maximum rate (calculated) = 63 g a. i./kg

- seed *(0.001 kg/1g)*(2.2 lb/ 1kg)*(1 kg

seed/2.2 lb

- seed)*(19.8 lb

- seed/A) = 1.25 lb a.i./A

Mammals

Hymexazol is classified as “slightly toxic” to mammals on an acute oral basis, however, the range of seed treatment application rate s ( 0.10 to 1.25 lb a.i./A) implies high residue concentrations on the treated seeds leading to LOC exceedances on both the acute and chronic levels. The high application rate (standard pellet) + high seeding rate scenario consistently
leads to LOC exceedances for sm all and medium size mammals when seeding rate is taken into account (i.e., RQ#2); however, in all scenarios and in particular on a dose basis , low end to high end, risk concern for mammals is high.

Table E1. Mammalian Seed Treatment RQs

-- for Tachigaren ® 70 WP as a single seed treatment application on sugar beets

Scenario 1 Mammalian (15 g) App rate (lbs a.i./A)

Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*)
High app rate / High seed rate 3.81 0.25 60.95 12.19 1.25

High app rate / Low seed rate 3.81 0.06 60.95 12.19 0.30

Low app rate / High seed rate 1.90 0.12 30.48 6.10 0.63

Low app rate / Low seed rate 1.90 0.03 30.48 6.10 0.15

High app rate (build up) / Low seed rate 1.27 0.02 20.32 4.06 0.10

Mammalian (35 g) App rate (lbs a.i./A)

Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*)
High app rate / High seed rate 3.25 0.13 52.07 10.41 1.25

High app rate / Low seed rate 3.25 0.03 52.07 10.41 0.30

Low app rate / High seed rate 1.63 0.07 26.03 5.21 0.63

Low app rate / Low seed rate 1.63 0.02 26.03 5.21 0.15

High app rate (build up) / Low seed rate 1.08 0.01 17.36 3.47 0.10

21 Note 0.70 is the fraction of hy mexazol active ingredient in the formulation ( i.e. , 70 % a.i. in Tachigaren® 70 WP EPA Reg. No. 48210

- 1)Mammalian (1000 g) App rate (lbs a.i./A)

Acute (# 1) Acute (# 2) Chronic (NOAEL*) Chronic (LOAEL*) High app rate / High seed rate 1.74 0.01 27.91 5.58 1.25

High app rate / Low seed rate 1.74 <0.01 27.91 5.58 0.30

Low app rate / High seed rate 0.87 0.01 13.95 2.79 0.63

Low app rate / Low seed rate 0.87 <0.01 13.95 2.79 0.15

High app rate (build up) / Low seed rate 0.58 <0.01 9.30 1.86 0.10

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)
*Bold values exceed acute listed and chronic listed and non

- listed species LOCs; highlighted cells signify values
that also exceed acute non

- listed LOCs

Acute RQ #1 = (mg a.i. /kg

- bw/day) / LD50

Acute RQ #2 = mg a.i. ft

- 2 /(LD50*bw)
Mammalian Chronic RQ = mg a.i./kg

- bw/day / adjusted NOAEL



### * The RQ is based on either the NOAEL or LOAEL as marked. The NOAEL = 100 mg/kg

- bw/day and LOAEL = 500 mg/kg

- bw/day based on the teratogenicity study (MRID 42826307). The LOAEL (the lowest observed adverse effect level) stands for the lowest tested concentration where effects are observed. In this study, the frank ef fect is reduced fetal weight. The teratogenicity study
showed reduced mean feta l weight (9.3% below control) at the highest tested concentration (also LOAEL: 500 mg a.i./kg

- bw), a dose which was not maternally toxic. As a result, the developmental NOAEL fo r the study is 100 mg a.i./kg

- bw. Additional developmental delays were also observed in the study. Though a 2

- generation reproduction study (MRID 42826309) suggests no treatment related effects on the general physical condition, body weight, or development al
landmarks of the F 1 

### and F 2 

### pups, post

- implantation s urvival rate and litter size were significantly reduced in the high dose (also LOAEL: 159 mg a.i./kg

- bw) F 1 

### (↓17%) and F 2 

### (↓20%) offspring compared to controls. Lower survival rates led to reduced lit ter size at birth/on postnatal day (PND) 1 in both the F 1 

### (↓26

- 27%) and F 2 

### (↓17%) generations. This reduction continued until PND 4 (pre

- cull), with 16% fewer F 1 

### pups and 19% fewer F 2 

### pups per litter compared to controls. It was impossible to determine if this was a maternal or in utero effect without more data; therefore, it was attributed to both. The paternal and offspring NOAEL in the 2

- generation study is 31 mg a.i./kg

- bw and furthe r supports the risk conclusions based on the development/teratogenicity study. Furthermore, the developmental NOAEL (100 mg/kg/day) is protective of the reproductive effects at 159 mg/kg/day in the 2

- generation study

. If this laboratory

- observed effect occurs in the environment, it could, in return, have effects on reproduction, survival, and growth of individuals and subsequent effects on a given mammalian population.

Birds Hymexazol is classified as “slightly toxic” to birds on an acute oral basis and “practically non

toxic” to birds on an acute dietary basis, ho wever, the range of seed treatment application

rate s ( 0.10 to 1.25 lb a.i./A) implies high residue concentrations on the treated seeds leading to LOC exceedances on both the acute and chronic levels. The high application rate (standard

### pellet) + high seedi ng rate scenario consistently leads to LOC exceedances for small and medium size birds when seeding rate is taken into account (i.e., RQ#2); however, in all

scenarios and in particular on a dose basis , low end to high end, risk concern for birds is high.

Table E2 . Avian Seed Treatment RQs

-- for Tachigaren ® 70 WP as a single seed treatment application on sugar beets

Scenario 1 Avian (20 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 18.08 0.74 164.23 65.73 1.25

High app rate / Low seed rate 18.08 0.18 164.23 65.73 0.30

Low app rate / High seed rate 9.04 0.37 82.12 32.86 0.63
Low app rate / Low seed rate 9.04 0.09 82.12 32.86 0.15

High app rate (build up) / Low seed rate 6.03 0.06 54.75 21.91 0.10

Avian (100 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 8.10 0.12 164.23 65.73 1.25

High app rate / Low seed rate 8.10 0.03 164.23 65.73 0.30

Low app rate / High seed rate 4.05 0.06 82.12 32.86 0.63
Low app rate / Low seed rate 4.05 0.01 82.12 32.86 0.15

High app rate (build up) / Low seed rate 2.70 0.01 54.75 21.91 0.10

Avian (1000 g) App rate (lbs a.i./A) Acute (# 1) Acute (# 2) Chronic (NOAEC*) Chronic (LOAEC*)
High app rate / High seed rate 2.57 0.01 164.23 65.73 1.25

High app rate / Low seed rate 2.57 <0.01 164.23 65.73 0.30

Low app rate / High seed rate 1.28 <0.01 82.12 32.86 0.63

Low app rate / Low seed rate 1.28 <0.01 82.12 32.86 0.15

High app rate (build up) / Low seed rate 0.86 <0.01 54.75 21.91 0.10

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

*Bold values exceed acute listed and chronic listed and non

- listed species LOCs; highlighted cells signify values that
also exceed acute non

- listed LOCs

Acute RQ #1 = (mg a.i. /kg

- bw/day) / LD50

Acute RQ #2 = mg a.i. ft

- 2 /(LD50*bw)

Avian Chronic RQ = mg kg

- 1 seed / NOAEL



### * The RQ is based on either the NOAEC or LOAEC as marked. The NOAEC = 385 mg a.i./kg

- diet and LOAEC = 962 mg a.i./kg

- diet based on the quail study (MRID 48716602). The LOAEC (the lowest observed adverse effect concentration) stands for the lowest tested concentration
where effects are observed. In this study, the frank effect is reduced eggshell thickness (5%

### reduction in thickness relative to the control at the highest dose level tested, 962 mg a.i./kg

diet)

. No other treatment related effects were observed in this study. However, in a reproduc tion study for the mallard (MRID 49268101), eggshell thickness was also significantly different (8.35% effect) relative to the control in the highest dose level tested (4467 mg a.i./kg

diet) , which led to a NOAEC of 902 mg a.i./kg

- diet

.

Seed Consumption A pproach Calculations
In an effort to refine the T

- REX outputs above, EFED calculated the amount of seeds mammals
and birds would need to consume to reach the acute risk (0.5 of the adjusted acute endpoint)

, acute endangered species risk (0.1 of the adjusted acute endpoint) , and chronic risk LOC levels.
Table E3 through Table E10 provide the following refinements: the number of sugar beet seed pellets ( i.e. , a raw seed with a pelleting mixture coating) that a 15, 35, and 1000g mammal and a 20, 100, and 1000g bird would need to consume, the percentage of the daily dietary intake of a given size class, and the area the organism would need to forage in order to attain the LOC. Consuming more seeds than reported in the tables would yield an LO C exceedance for that risk category. The following assumptions were made: the lowest and highest seeding rates available

in T

- REX were used (i.e., 4.8 and 19.8 lb seeds/acre, respectively), that the mammals and birds assessed are granivores, and, as a resu lt, the mass fraction of water in the food items is 0.1

– i.e. relevant for determination of the daily mass food intake. A detailed description of sample
calculations can be found in Appendix D

.

Mammals
The values in Table E3 through Table E6 provide est imates of seed consumption ( i.e., #pellets consumed) and forage area ( i.e., area covered) for mammals under the same five scenarios presented in the above T

- REX calculations. The seed consumption to reach the given threshold changes with application rate ( i.e., recall that application rate determines the amount of a.i. on a seed pellet) , while forage area covered to consume enough seeds to reach a given risk level changes with both the application rate and seeding rate. A lower seeding rate always leads to a higher foraging area, which would effectively minimize the exposure of the organism on a per
area basis.

Table E3 and Table E4 focus on seed consumption and forage area to reach the acute and acute listed LOC, respectively. Table E5 and Table E6 present seed consumpti on and forage area to
reach the chronic LOC using the weight adjusted NOAEL and LOAEL (or frank effects endpoint), respectively. The ‘adjustment’ to the endpoints refers to the body weight adjustment to the
three size classes of mamm als ( see T

- REX User Guide).

Using the nocturnal wood (or field) mouse 22 

### or Apodemus sylvaticus (belonging to the small to medium mammalian size class; i.e., 13

- 27g) as a case example we show that the calculated

22 Putman, R.J. Ed. 1989. Mammals as Pests. Chapter 3: The Mammal Society. New York, New York. ISBN: 0 412
32590X. Available online: https://books.google.com/books?hl=en&lr=&id =hOEM7IC8XhUC&oi=fnd&pg=PA34&dq=predators+beet+seed& ots=1A5O3k9AOe&sig=YYtp2NCmrexgDhVGJ24x2F0QloI&safe=on#v=onepage&q=predators%20beet%20seed
&f=false

### consumption rates are plausible. The wood mouse is an abundant granivore that feeds on sugar beet seeds. It can easily locate them by smell and excavate them from the soil. It removes the
seed coat orally and consumes the plant embryo. A single wood mouse can, on average, consume 800 seeds in one night; the highest consumption by a single individual is reported to be 1400 seeds in one night 23 

### . That is, assuming the wood mouse only feeds on sugar beets. The forage area is 10

- 20 m along a row followed by move ment to an adjacent row. The mouse can detect ungerminated sugar beet seeds at depths of at least 3 cm ; rabbits ( Oryctolagus
cuniculus ) and hares ( Lepus capensis ) also feed on cotyledons, leaves, petioles, and crowns of sugar beet plants 24



### .

Assuming the average consumption rate of 800 seeds/night, the wood mouse could easily consume enough pelleted seeds to reach and exceed LOCs for the acute (84 seeds/day), listed (17 seeds/day), chronic (10 seeds/day), and frank effects chronic (52 seeds/da y) risk categories at the low end scenario ( i.e. , low application rate and low seeding rate ) for the standard pellet

. With respect to the high application rate for the build

- up pellet and the low seeding rate, the most compelling result is for the chronic values whereby the wood mouse could conceivably

consume over 16 pellets/day (or 64% of its daily mass intake) to exceed the adjusted NOAEC.

Taking the less conservative approach and assuming a typical 25 

### sugar beet row spacing of 22 inches (or 0.5588 m), t he minimum row forage distance (10m) of the wood mouse 22 

### , and that the wood mouse only reaches two consecutive rows to forage, the forage area covered is

5.588m 2 

### (or 60 ft 2 

### ). Therefore, the wood mouse can cover 60 ft 2 

### and in that area encounter enough pell eted seeds to reach and exceed LOCs for the acute (17 ft 2 

### ), listed (3 ft 2 

### ), chronic (2
ft 2 

### ), and frank effects chronic (10 ft 2 

### ) risk categories at the low end scenario ( i.e. , low application rate and low seeding rate). With respect to the high application rate for the build

- up pellet and the low seeding rate, the wood mouse would cover only 3.13 ft 2 

### to obtain enough seeds ( i.e., 16 pellets/day) to reach the adjusted NOAEC.

Though larger size mammals require consumption of a greater number of pellets and a larger foraging area to reach the given risk categories, the potential of reaching or exceeding the LOC levels is high, especially for the high application rate (standard pellet) + high seeding rate scenarios and even more so in the cases of acute exposure to listed species and chronic exposure in general.

23 Putman, R.J. 1989 citing Pelz 1979.

24 Draycott, A.P. Ed. 2006. Sugar Beet. Chapter 13: Pests. Blackwel l Publishing. ISBN

- 10: 1

- 4051

- 1911

- X. ISBN

13: 978

- 1

- 4051

- 1911

- 5. Available online: https://books.google.com/books?id=h1hMU

uA59QC&pg=PA341&lpg=PA341&dq=birds+feeding+on+sugar+beet+seeds&source=bl&ots=xxfn0cjEe 5&sig=_r vKXnq77KSfc9jJ0DhurvsvEKg&hl=en&sa=X&ved=0CDAQ6AEwBWoVChMIvtS6sLTbxgIVBXs

Ch3rywuh#v=onepage&q=birds%20feeding%20on%20sugar%20beet%20seeds&f=false

25 Minimum row spacing is 15 inches (or 0.381m). (EPA draft guidance)Table E3. Acute Risk to Mammals: Comparisons to 0.5 Adj. LD 50 Scenario 1 (app rate/seed rate) 0.5 Adjusted

LD 50 (mg a.i./kg

bw) Mass of a.i.
to reach 0.5 adj LD 50 (mg a.i.) Mass of pellet to
reach 0.5 adj. LD 50 (mg

pellet) # Pellets
consumed
to reach 0.5 adj.

LD 50 Daily
mass of
food

intake (mg) Fraction of Daily
mass intake to reach 0.5 adj.

LD 50 (%)* Area
covered (ft 2 )**

15 g size class High/High 1,758 26 1,256 42 3,178 39.5 2.02 High/Low 8.36 Low/High 2,512 84 79 4.04 Low/Low 16.71 High (build up)/Low 16,330 126 514 25.1

35 g size class High/High 1,423 50 2,371 79 5,125 46.3 3.82 High/Low 15.78 Low/High 4,742 158 92.5 7.64 Low/Low 31.55 High (build up)/Low 30,830 237 602 47.34

1000 g size class High/High 615 615 29,301 977 33,951 86.3 47.2 High/Low 194.95 Low/High 58,603 1,953 172.6 94.4 Low/Low 389.9 High (build up)/Low 381,008 2,931 1,122 585

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

The LD 50 = 1600 mg a.i./kg

- bw for a 350g rat. The adjusted LD 50 = 3,517 mg a.i./kg

- bw for a 15g mammal, 2,845 mg a.i./kg

- bw for a 35g mammal, and 1231 mg a.i./kg

- bw for a 1000g mammal *(Mass of pellet to reach 0.5 adjusted LD 50 / Daily mass intake) x 100 **Number of pellets consumed to reach the 0.5 adjusted LD 50 / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)

Table E4 . Acute Endangered Mammal Species Risk: Comparisons to 0.1 Adj. LD 50

Scenario 1 (app rate/seed rate) 0.1 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to

reach 0.1 adj LD 50 (mg a.i.) Mass of pellet to

reach 0.1 adj. LD 50 (mg

pellet) # Pellets
consumed

to reach

0.1 adj.

LD 50 Daily
mass of

food
intake (mg) Fraction of Daily
mass intake to reach 0.1 adj.

LD 50 (%)* Area
covered (ft 2 )**

15 g size class High/High 352 5.3 251 8 3,178 7.9 0.40 High/Low 1.67 Low/High 502 17 15.8 0.81 Low/Low 3.34 High (build up)/Low 3,266 25 103 5.0135 g size class High/High 285 10 474 16 5,125 9.3 0.76 High/Low 3.16 Low/High 948 32 18.5 1.53 Low/Low 6.31 High (build up)/Low 6,166 47 120 9.47

1000 g size class High/High 123 123 5,860 195 33,951 17.3 9.44 High/Low 38.99 Low/High 11,721 391 34.5 18.87 Low/Low 77.98 High (build up)/Low 76,202 586 224 117

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)
The LD 50 = 1600 mg a.i./kg

- bw for a 350g rat. The adjusted LD 50 = 3,517 mg a.i./kg

- bw for a 15g mammal, 2,845 mg a.i./kg

- bw for a 35g mammal, and 1231 mg a.i./kg

- bw for a 1000g mammal *(Mass of pellet to reach 0.1 adjusted LD 50 / Daily mass intake) x 100
**Num ber of pellets consumed to reach the 0.1 adjusted LD 50 / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)

Table E5 . Chronic Risk to Mammals: Comparisons to Adj. NOAEL

Scenario 1 (app rate/seed rate) Adjusted

NOAEL (mg a.i./kg

bw) Mass of

a.i. to reach adj

NOAEL (mg a.i.) Mass of pellet to reach adj.

NOAEL (mg

pellet) # Pellets

consumed
to reach adj. NOAEL Daily

mass of
food
intake (mg) Fraction of Daily

mass intake to reach adj. NOAEL (%)* Area

covered (ft 2 )**

15 g size class High/High 220 3.3 157 5 3,178 4.9 0.25 High/Low 1.04 Low/High 314 10 9.9 0.51 Low/Low 2.09 High (build up)/Low 2,041 16 64.2 3.13

35 g size class High/High 178 6.2 296 10 5,125 5.8 0.48 High/Low 1.97 Low/High 593 20 11.6 0.95 Low/Low 3.94 High (build up)/Low 3,854 30 75.2 5.92

1000 g size class High/High 77 76.9 3,662 122 33,951 10.8 5.90 High/Low 24.37 Low/High 7,325 244 21.6 11.8 Low/Low 48.74 High (build up)/Low 47,626 366 140.3 73.12

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)The NOAEL = 10 0 mg a.i./kg

- bw for a 350g rat (based on teratogenicity study, MRID 42826307) *(Mass of pellet to reach adjusted NOAEL / Daily mass intake) x 100 **Number of pellets consumed to reach the adjusted NOAEL / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)

Table E6 . Chronic Risk t o Mammals: Comparisons to Adj. L OAEL

Scenario 1 (app rate/seed rate) Adjusted

L OAEL (mg a.i./kg

bw) Mass of

a.i. to reach adj

L OAEL (mg a.i.) Mass of pellet to reach adj.

L OAEL (mg

pellet) # Pellets
consumed

to reach adj. L OAEL Daily
mass of

food
intake (mg) Fraction of D aily
mass intake to reach adj. L OAEL (%)* Area
covered (ft 2 )**

15 g size class High/High 1,099 16.5 785 26 3,178 24.7 1.26 High/Low 5.22 Low/High 1,570 52 49.4 2.53 Low/Low 10.4 High (build up)/Low 10,207 79 321 15.7

35 g size class High/High 889 31.1 1,482 49 5,125 28.9 2.39 High/Low 9.86 Low/High 2,964 99 57.8 4.77 Low/Low 19.7 High (build up)/Low 19,269 148 376 29.6

1000 g size class High/High 385 385 18,313 610 33,951 53.9 29.5 High/Low 121.8 Low/High 36,627 1,221 108 58.98 Low/Low 243.7 High (build up)/Low 238,130 1,832 701 365.6

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

The LOAEL = 5 0 0 mg a.i./kg

- bw for a 350g rat (based on teratogenicity study, MRID 42826307) *(Ma ss of pellet to reach adjusted L OAEL / Daily mass intake) x 100 **Number of pellets consumed to reach the adjusted L OAEL / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)



### Birds
The values in Table E7 through Table E10 provide estimates of seed consumpti on ( i.e., #pellets consumed) and forage area ( i.e., area covere d) for birds under the same five scenarios presented in the above T

- REX and SCA mammalian calculations. As for the mammals, the seed consumption to reach the given threshold changes with application rate ( i.e., recall that application rate determines the amount of a.i. on a seed pellet) , while forage area covered to consume enough seeds to reach a given risk level changes with both the application rate and seeding rate. A low er seeding rate always leads to a higher foraging area, which would effectively minimize the exposure of the organism on a per area basis.

### Table E7 and Table E8 focus on seed consumption and forage area to reach the acute and acute listed LOC, respectivel y. Table E9 and Table E10 present seed consumption and forage area to reach the chronic LOC using the avian NOAEL and LOAEL (or frank effects endpoint), respectively. The weight adjustment is not calculated for birds as no data exist for incorporating

sca ling factors for birds.

Using the zebra finch 26 

### or Taeniopygia guttata (belonging to the small avian size class; i.e., 12.7g) as a case example we show that the calculated consumption rates are plausible. The zebra finch is a passerine granivore but may al so feed on fruits and vegetables 27 

### . Though little information is available on the finch’s sugar beet seed consumption, one open literature study (Lemon & Barth 1992) notes that when fed a diet of mixed grass seeds without seed hulls or chaff, a single zebra finch adult could consume approximately 2.3g of seeds per day. Furthermore, birds like skylarks ( Alauda arvensis ), house sparrows ( Passer domesticus L.),

pa r tridges ( Perdix perdix L.), woodpigeons ( Columba palumbus L.), and pheasants ( Phasianus
colchicus ) feed on sugar beet seedlings and foliage; rooks ( Corvus frugilegus ) can uproot them in search of soil invertebrates; and, skylarks can also feed on sugar beet cotyledons 24



### .

Assuming the grass seeds approximate a standard pelleted sugar beet seed in weight (30 mg, or 0.03 g, see Appendix D ), the consumption rate of sugar beet seeds for comparison with calculations becomes 77 seeds/day ; for build

- up pellets (130 mg is 0.13g) be comes 18 seeds/day . With this in mind, the zebra finch could easily consume enough pelleted seeds to reach and exceed LOCs for the acute (28 seeds/day), listed (6 seeds/day), chronic ( 6 seeds/day ), and frank effects chronic (15 seeds/day) risk categor ies a t the low end scenario ( i.e. , low application rate and low seeding rate ) for the standard pellet . The fraction of the daily mass intake is less than 20% for acute exposure meaning that the zebra finch would not have to consume a lot of sugar beet seed to r each the acute risk categories.

With respect to the high application rate for the build

- up pellet and the low seeding rate, the most compelling result s are for the acute listed, chronic , and frank effects chronic risk categories whereby the zebra finch c ould conceivably consume over 8 pellets/day (or 22 % of its daily mass intake), 40 pellets/day (23.8%), and 101 pellets/day (59.6%), respectively, to exceed

the LOCs

.

Taking the less conservative approach, as was calculated for the wood mouse, and assuming a typical 28 

### sugar beet row spacing of 22 inches (or 0.5588 m), the minimum row forage distance (10m) of the wood mouse 22 

### (since data on the zebra finch is not available), and that the zebra

26 Lemon, W.C. and R.H. Barth, J r. 1992. The effects of feeding rate on reproductive success in the zebra finch, Taeniopygia guttata

. Animal Behavior (44): 851

- 857.

Available online: http://ac.els

- cdn.com/S0003347205805810/1

- s2.0

- S0003347205805810

- main.pdf?_tid=cebfcac2

- 2587

- 11e5

- b1ee

00000aacb35f&acdnat=1436370272_c91241597d91c91a2f01627aa3c043a0

27 http://www.finchinfo.com/diet/safe_toxic_and_unsafe_foods.php

28 Minimum row spacing is 15 inches (or 0.381m). (EPA draft guidance)

### finch only reaches two consecutive rows to forage, the forage area covered is 5.588m 2 

### (or 60
ft 2 

### ). Therefore, the zebra finch can cover 60 ft 2 

### and in that area encounter enough pelleted seeds to reach and exceed LOCs for the acute (6 ft 2 

### ), listed (1 ft 2 

### ), chronic (1 ft 2 

### ), and frank effects chronic (3 ft 2 

### ) risk catego ries at the low end scenario ( i.e.

, low application rate and low seeding rate) for the standard pellet

. With respect to the high application rate for the build

- up pellet and the low seeding rate, the zebra finch would cover only 2, 8 and 20 ft 2 

### to obtain enough seeds ( i.e., 8, 40, 101 pellets/day) to reach the adjusted LD 50 

### , non

- adjusted NOAEL and LOAEL for the acute listed, chronic, and frank effects chronic risk categories, respectively.

Though larger size birds require consumption of a greater number of pellets and a larger foraging area to reach the given risk categories, the potential of reaching or exceeding the LOC levels is high, especially for the high application rate (standard pellet) + high seeding rate
scenarios and even more so in the cases of acute exposure to listed species and chronic exposure in general.

Table E7 . Acute Risk to Birds: Comparisons to 0.5 Adj. LD 50

Scenario 1 (app rate/seed rate) 0.5 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to
reach 0.5 adj LD 50 (mg a.i.) Mass of pelle t to reach 0.5 adj.

LD 50 (mg

pellet) # Pellets
consumed
to reach 0.5 adj. LD 50 Daily mass
of food intake (mg) Fraction of Daily mass
intake to

reach 0.5 adj. LD 50 (%)* Area
covered (ft 2 )**

20 g size class High/High 443 8.9 422 14 5,062 8.3 0.68 High/Low 2.8 Low/High 843 28 16.7 1.36 Low/Low 5.61 High (build up)/Low 5,482 42 108 8.42

100 g size class High/High 564 56 2,683 89 14,432 19 4.32 High/Low 17.85 Low/High 5,367 179 37.2 8.64 Low/Low 35.71 High (build up)/Low 34,893 268 242 53.6

1000 g size class High/High 796 796 37,904 1,263 64,615 59 61.04 High/Low 252. 2 Low/High 75,808 2,527 117.3 122. 1 Low/Low 504. 4 High (build up)/Low 492,870 3,791 763 756.8

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

The LD 50 = 827 mg a.i./kg

- bw for a 12.7 g passerine. The adjusted LD 50 = 885 mg a.i./kg

- bw for a 20g bird, 1,127 mg a.i./kg

- bw for a 100g bird, a nd 1,592 mg a.i./kg

- bw for a 1000g bird *(Mass of pellet to reach 0.5 adjusted LD 50 / Daily mass intake) x 100 **Number of pellets consumed to reach the 0.5 adjusted LD 50 / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)Table E8. Acute Endangered Bird Species Risk: Comparisons to 0.1 Adj. LD 50 Scenario 1 (app rate/seed rate) 0.1 Adjusted

LD 50 (mg a.i./kg

bw) Mass of

a.i. to

reach 0.1 adj LD 50 (mg a.i.) Mass of pellet to

reach 0.1 adj. LD 50 (mg

pellet) # Pellets
consumed

to reach 0.1 adj. LD 50 Daily mass
of food intake (mg) Fraction of Daily mass

intake to
reach 0.1 adj. LD 50 (%)* Area
covered (ft 2 )**

20 g size class High/High 88.5 1.8 84 3 5,062 1.7 0.14 High/Low 0.56 Low/High 169 6 3.3 0.27 Low/Low 1.12 High (build up)/Low 1,096 8 22 1.68

100 g size class High/High 113 11 537 18 14,432 3.7 0.86 High/Low 3.57 Low/High 1,073 36 7.4 1.73 Low/Low 7.14 High (build up)/Low 6,979 54 48 10.7

1000 g size class High/High 159 159 7,581 253 64,615 12 12.21 High/Low 50.44 Low/High 15,162 505 23.5 24.4 Low/Low 100.9 High (build up)/Low 98,574 758 153 151.4

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

The LD 50 = 827 mg a.i./kg

- bw for a 12.7 g passerine. The adjusted LD 50 = 885 mg a.i./kg

- bw for a 20g bird, 1,127 mg a.i./kg

- bw for a 100g bird, and 1,592 mg a.i./kg

- bw for a 1000g bird *(Mass of pellet to reach 0.1 adjusted LD 50 / Daily mass intake) x 100
**Nu mber of pellets consumed to reach the 0.1 adjusted LD 50 / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)

Table E9 . Chronic Risk to Birds: Comparisons to NOAEC

Scenario 1 (app rate/seed rate) NOAEC (mg a.i./kg

diet ) Mass of

a.i. to
reach

NOAEC (mg a.i.) Mas s of pellet to
reach

NOAEC (mg

pellet) # Pellets
consumed
to reach

NOAEC Daily
mass of
food

intake (mg) Fraction of Daily
mass intake to
reach NO AEC (%)* Area
covered (ft 2 )**

20 g size class High/High 385 1.95 92.8 3 5,062 1.8 0.15 High/Low 0.62 Low/High 186 6 3.7 0.30 Low/Low 1.23 High (build up)/Low 1,207 40 23.8 8.03

100 g size classHigh/High 385 5.56 265 9 14,432 1.8 0.43 High/Low 1.76 Low/High 529 18 3.7 0.85 Low/Low 3.52 High (build up)/Low 3,441 115 23.8 22.89

1000 g size class High/High 385 24.9 1,185 39 64,615 1.8 1.91 High/Low 7.88 Low/High 2,369 79 3.7 3.82 Low/Low 15.76 High (build up)/Low 15,404 513 23.8 102.5

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario)

The NOAEL = 385 mg a.i./kg

- diet (based on bobwhite quail study MRID 48716602 ) *(Mass o f pellet to reach NOAEC / Daily mass intake) x 100
**Number of pellets consumed to reach NOAEC / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)

Table E10 . Chronic Risk t o Birds: Comparisons to LOAEC

Scenario 1 (app rate/seed rate) LOAEC (mg a.i./kg

diet ) Mass of

a.i. to
reach

LOAEC (mg a.i.) Mass of pellet to
reach

LOAEC (mg

pellet) # Pellets
consumed
to reach

LOAEC Daily
mass of
food

intake (mg) Fraction of D aily
mass intake to
reach LOAEC (%)* Area
covered (ft 2 )**

20 g size class High/High 962 4.9 232 8 5,062 4.6 0.37 High/Low 1.54 Low/High 464 15 9.2 0.75 Low/Low 3.09 High (build up)/Low 3,015 101 59.6 20.1

100 g size class High/High 962 13.9 661 22 14,432 4.6 1.06 High/Low 4.40 Low/High 1,322 44 9.2 2.13 Low/Low 8.80 High (build up)/Low 8,597 287 59.6 57.2

1000 g size class High/High 962 62.2 2,960 99 64,615 4.6 4.77 High/Low 19.7 Low/High 5,920 197 9.2 9.53 Low/Low 39.4 High (build up)/Low 38,489 1,283 59.6 256.1

1 High and low app rates are for the standard pellet use unless otherwise specified (i.e., the fifth scenario) The LOAEC = 962 mg a.i./kg

- diet (based on bobwhite quail study MRID 48716602 ) *(Ma ss of pellet to reach LOAEC / Daily mass intake) x 100
**Number of pellets consumed to reach LOAEC / ( 20.7 or 5.01) seed pellets ft

- 2 (See Appendix D for details)