UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D.C. 20460

MEMORANDUM

Date: 09-SEP

- 2014 OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVENTION

SUBJECT: Hexythiazox. Human Health Risk Assessment to Support Emergency Exemption U se inion Sugar Beet.

PC Code: 128849 DP Barcode: D421443

Decision No.: 493021 Registration No

. : 10163-277

Petition No

. : 14ID02 Regulatory Action: Section 18

Risk Assessment Type: Single Chemical Aggregate

TXRNo

. : NA

MRlDNo .: NA

FROM: Kate! ynn King

, Risk Assessor

Alexandra LaMay, Bio l og i st
Linda Tay l or, Toxicologist Registration

Case No

. : N / A

CAS No.: 78587

- 05-0

40 CFR : 180.448



### (_

Risk Assessment Branch V

Health E ffects Division (7509P)

THROUGH: Danette Drew, Chemist

# ~**t~CJ,. ~~**  William Donovan, Chemis r

- /}
Michael Metzger, Chief {)..4_4

Risk Assessment Branch II

Health Effects Division (7509P)

TO: Tawanda Maignan, Risk Manager 09
Andrea Conrath, Risk Manager Rev i ewer Risk Integration, Minor Use & Emergency Response Branch Registration Division (7505P)

Page 1 of32Hexyth i azo x Human Health R i s k Assessmen t D 421443

Table of Contents

1

. 0 Executive Summary

........ .. .......... .. .. .. .. .. .. .. . ... ... . .......................... .. .. ... .. .. .. .. .. ... . ... ... 4

2

. 0 HED Recommendations

.. . .. . ........................... . ... . ... .. . .. .. .. ... .. . .. .. ... ........................ . 5
2.1 Data Deficiencies

................. .. . ... . .. .. .. .. .. .. .. .. .. ... . .................. . ..... . . ... . ... .. .. .. ... . . .. .. .. 5

2.2 Tolerance Considerations

.................................. .. .. .. .. .. .. .. .. .. .. ... . ....... . . ............... 5
2.2.1 Enforcement Analytical Method

. . .. .. .. .. . ......... .. ............. .. . ............ . ... . ... .. .. .. ... 6
2.2.2 Recommended Tole rances

.. . ..................... .. .. .. .. .. .. .. .. .. .. .. .. .. ... . ....................... 6
2.2.3 Revisions to Petitioned-For Tolerances

. . .......................... . .. .. .. .. .. .. .. ... . ... . ..... 6
2.2.4 International Harmonization

.................. ... ... . .. .. .. .. .. .. .. .. .. .. ... .. .. .. . .................. 6
2.3 Label Recommendations

....... . ...... . ... . .. .. .. ... . ... . ... .. .. . ... .................. . ......... . . ... .. .. .. . 7
2.3.1 Recommendations from Residue Reviews

............ . .. . . ... . ... . ... . ... .. .. .. .. .. ... . ...... 7
2.3.2 Recommendations from Occupational Assessment

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

2

. 3 .3 Recommendations from Residential Assessment..

.. .. .. .. . ........ ... .................. . 7
3.0 Introduction

.. . ..... . . .......... . .. .. .. .. .. . ... .. .. . .. .. ... . .. ............................... . ...... ... .. .. .. ... .. .. .. .. 7
3

. 1 Chemical Identity

. . ...... . ...................................... ... . .. .. .. .. .. .. .. .. .. .. ... . ... .. ............... 7
3.2 Physical/Chemical Characteristics

. .. .. .. .. .. .. ... . .. ........................................ .. . ... .. 8

3.3 Pesticide Use Pattern

. ................ . ................ . ....... .. . .. .. ... . .. ... .. . ... . ... .. .. .. ... .. . ... .. ..... 9
3.5 Consideration of Env ironmental Justice

........... . . . . ..... . ... . ... . ... .. .. .. .. .. .. .. ... .. .. .. ... 9
4.0 Hazard Characterization and Dose

- Response Assessment

.......... . .. . .. .. ....... . ... . 10
4.1 Hazard Characterization

................... . ... . . ... . ... . ... .. .. .. .. .. .. .. .. .. ....... . ... . ... . .... ..... . . 10
4.2 Hazard Profile

..... .. .......... . .. . ... . .. .. . ... .. .. . ... .. .. .. . ... . ... . .......................................... 11
4.3 Dose-Response Assessment/Endpoint Selection

.. .. .................... . ............ ... .. .. 11
4.4 FQPA Considerations

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

4.5 Summary of Toxicological Doses and Endpoints for Use in Human Risk
Assessments and Levels

.. . ... . ...... . .. .. .. .. .. . ... . ... .. .......... .. ............................ . .................... 12
5.0 Dietary Exposure/Risk Characterization

. .. .. .. ... .. . ... . ... . .. .. ... .. .. . ... . ... .. .. ... . ... .. .. .. . 1 4
5.1 Residue Chemistry Summary

... . .. ... .. . ... . .. .. .. .. ... . .. ..... . .. . ..................... . ............ 14
5.2 Drinking Water Residue Profile

..................... . ..... . ... .. .. . ........ . ... .. .. ... .. ....... . ... . 15

5.3 Dietary Exposure and Risk

.. .. .. .. . .. .. .. .. .. .. .. ... .. . ... . ... . ....... .. ...... .. . ........ . ....... .. .... 1 5
5.4 Anticipated Residue and Percent Crop Treated (%CT) Information

. .. .. ... 17
6.0 Residential and Other N on-Occupationa l Exp osures/Risks

.. .. ... . .. ... .. .. .. .. ... .. . . 17
6.1 Residential Handler Exposure and Risk

.................................................. . ..... 17
6.2 Residential Post

- application Exposure

........................................................... 17

6

. 3 Other

... . .. . .. . ... . .. . .. .. .. . .. .. .. .. .. . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... . ... .. .. .. .. 19
7.0 Aggregate Risk Assessments and Risk Characterization

.. .. . . .... .. .. .. . .. ... .. .. .. ... .. 20
7.1 Acute Aggregate Risk.

.............................................................. . ....... . ............ . .. 20

7.2 Short

- and I ntermediate-Term Aggregate Risks

. . ... .. .. . ... .. .. . ... . .... . .. .. .. .. ... . ... 20

7

. 3 Long-Term (Chronic) Aggregate Risk

........................................................... 20

8.0 Cumulative Risk Characterization/ Assessment

... . ... . ... .. .. .. .. . ... .. . .. ... .. . ... ... . ... .. .. 21
9.0 Occupational Exposures and Risks

. . ...... .. .. .. ... . ...... .. ....... .. .. . .. ... ..... ... .. .. .. .. .. .. ... .. 21
9.1 Occupational Handler Risk

............................................ . ................ . ........ ....... 21
9.2 Occupational Post Application Risk

. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... . . .. .. .. .. .. ... .. 21
10

. 0 Human Studies

............. . ..................................................................... . ................. 23 Appendix A

. Tox i cology Assessment..

.. .. .. . ....... . ........... . ... .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... .. . ... .. .. .. .. . 24 Appendix B: Toxicology Data Requirements

................ ...... .......... ..................... . ............. 28 Appendix C : Field T ri a l Res idu e Data

. ... . ...... .. .. . ............... .. ... . ....... . ... . ... . ... . ... . ... .. .. . ... .. ... . 29

Page 2 of32Hexythiazox Human Health Risk Assessment D313192

Page 3 of 32 Appendix D: Maximum Residue Limits (MRL)

................................ .............................. 30 Appendix E: OECD Calculator MRL Output

................................ ................................ ... 31 Appendix F: Estimated Drinking Water Concentration

................................ .................... 32Hexythiazox Human Health Risk Assessment D313192

Page 4 of 32 1.0 Executive Summary

Hexythiazox, trans

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxothiazol idine

- 3

- carboxamide, is an ovicide/miticide used to control spotted spider mites on a variety of

crops and outdoor residential settings . Hexythiazox is a contact pesticide which achieves control of eggs or immature mites via direct contact or contact with treated surfaces.

The Idaho State Department of Agriculture (ISDA) is applying for a FIFRA S ection 18

emergency specific exemption for the use of hexythiazox, formulated as the product Onager Miticide on sugar beets in Idaho and Oregon. Gowan submitted the results of
residue studies conducted with a target application rate of 0.1875 lb of ai/A and a target

pre

- harvest interval ( PHI ) of 45 days. One decline study was conducted depicting residues over a PHI range of 38

- 66 days , showing little change in residues over this time
interval

. The proposed supplemental Onager ® Miticide label specifies a PHI of 21 days for sugar beet ; however

, the submitted residue data support a minimum PHI of 3 8 day s. The use directions for sugar beet should be changed to indicate a minimum PHI of 38 days. With this modification, the residue data support a tolerance level of 0.15 ppm for sugar beet roots.

The toxicity database for hexythiazox is complete. Hexythiazox is associated with toxicity of the liver and adrenals following sub

- chronic and chronic exposure to dogs, rats and mice, with the dog bei ng the most sensitive species. The prenatal development al
studies in rabbits and rats and the two

- generation reproduction study in rats showed no indication of increased susceptibility to in utero and/or postnatal exposure to hexythiazox. Reproductive toxicity was not observed. There is no concern for

neurot oxicity following exposure to hexythiazox. The toxicology database for hexythiazox does not show any evidence of treatment

- related effects on the immune
system. Hexythiazox is classified as “likely to be carcinogenic to humans”; however,

s ince the effects seen in the study that serves as the basis for the chronic reference dose (RfD) occurred at doses substantially below the lowest dose that induced tumors, HED concluded that quantification of risk using a non

- linear approach; i.e., RfD, for hexythiazox wil l adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to hexythiazox.

No acute risk is expected since no hazard was identified in any toxicity study for this duration of exposure. Chronic risk is regul ated based on effects seen in the adrenal glands in a one

- year dog feeding study. Short

- term and intermediate

- term incidental oral and inhalation risks are regulated based on decreased pup body weight during lactation
and delays in hair growth and/or eye opening, decreased p arental body

- weight gain and
increased liver, kidney, and adrenal weights in the 2

- generation reproduction study in the

rat. For the short

- and intermediate

- term dermal risk assessment, no quantification of risk is required

. As no dermal hazard has been identified for hexythiazox, quantification of dermal post

- application risk is not required. For the short

- term and intermediate

- term dermal risk assessments, no quantification of risk is required, based on the fact that the dermal eq uivalent dose for this dermal exposure scenario is 1.5

- fold greater than the limitHexythiazox Human Health Risk Assessment D313192

Page 5 of 32 dose considering the NOAEL of 30 mg/kg/day from the oral reproduction study, and the estimated 2% dermal absorption for this compound.

An acute endpoint was not selected fo r hexythiazox; therefore, the Agency conducted only a chronic dietary (food and drinking water) exposure and risk assessment. The chronic dietary risk assessment used tolerance level residues

, assumed 100% crop treated

, included DEEM default processing fa ctors, and modeled water values . This unrefined
assessment resulted in estimated chronic dietar y (food and water) risks of 17 % of the chronic population adjusted dose (cPAD) for the U.S. population an d 82 % of the cPAD
for children 1

– 2 years of age, the most highly exposed population subgroup.

Since there are no acute endpoints of concern, an acute aggregate risk assessment was not
conducted. HED has conducted short

- term, intermediate

- term

, and lon g

- term (chronic)
aggregate (food, drinking water and r esidential ) risk assessments for hexythiazox. Short

and intermediate

- ter m aggregate MOEs ranged from 1,300 to 9,8 00; significantly exceeding the LOC of 100 and are not of concern. The long

- term (chronic) aggregate assessment includes only dietary (food and water) exposure as there are no long

- term residential exposure s cenarios. Chronic dietary risk is not of concern.

A quantitative dermal risk assessment is not required for hexythiazox. Occupational
handler inhalation MOEs significantly exceed 100 for all scenarios assessed associated
with the new use and are not of concern . Further, there were no risks of concern identified for postapplication exposure to hexythiazox associated with th is new use.

No additional personal protective equipment (PPE) is required

. T he label restricted entry interval (REI) of 1 2 hours is appropriate and in compliance Worker Pro tection Standard requirements.

Potential areas of environmental justice concern, to the extent possible, were considered
in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

Income Populations," http://www .eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

2.0 HED Recommendations

Provided the proposed label is amended as noted in Section 2.3 .1 , there are no hazard, exposure, or risk considerations that would preclude granting the requested emergency exemption use on sugar beets

, and setting the recommended tolerance described in
Section 2.2.2.

2.1 Data Deficiencies

There are no data deficiencies with respect to chemistry, ORE , and toxicology associated
with this action.

2.2 Tolerance ConsiderationsHexythiazox Human Health Risk Assessment D313192

Page 6 of 32 2.2.1 Enforcement Analytical Method

Hexythiazox and its metabolites are not consistently recovered through FDA’s multi

residue methods. No data were provided, or are required, for recovery through other
common multi

- residue methodology.

An adequate HP LC/UV analytical method is available for the enforcement of tolerances for residues of hexythiazox and its metabolites containing the PT

- 1

- 3 moiety in crop and
livestock commodities. This method is listed in the U.S. EPA Index of Residue Analytical Methods under hexythiazox as method AMR

- 985

- 87.

Briefly, residues are extracted with methanol or methanol/water, acidified, partitioned
with dichloromethane (DCM) , subjected to base hydrolysis, partitioned with acetonitrile,
and re

- partitioned with DCM. The e xtracts are cleaned up using column chromatography, and the ethyl acetate/hexane eluate is concentrated and analyzed by
HPLC with UV detection. Residues are expressed in terms of hexythiazox using a molecular weight conversion factor of 1.55. The method L OQ is 0.02 ppm.

2.2. 2 Recommended Tolerances

Tolerances currently established under 40 CFR §180.448 comply with the HED Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09); therefore, no revisions are
recommended to the residue definition. T able 2.2.2 summarizes the recommended tolerance level and commodity definition required to support the proposed new emergency exemption use on sugar beets . This tolerance should be added to 40 CFR §180.448(b)

.

Table 2.2.2 . Tolerance Summary for Hexythia zox

. Commodity Proposed Tolerance (ppm) HED

- Recommended

Tolerance (ppm) Comments

( correct commodity definition )

Sugar Beet Roots NA 0.15 Beet, sugar, root ; expiration date TBD

2.2. 3 Revisions to Petitioned

- For Tolerances

No tolerances were propos ed by the petitioner

. HED used the OECD tolerance calculation procedure s to determine a recommended tolerance level of 0.15 ppm for sugar
beet roots. T he results of the OECD MRL calculations are present ed in Appendix E.

2.2. 4 International Harmonizati on

The International Residue Limit (IRL) status sheet is included as Appendix D to this
memorandum. As there are no Codex or Canadian MRLs for hexythiazox in/on sugar beets, there are no harmonization issues associated with this action.Hexythiazox Human Health Risk Assessment D313192

Page 7 of 32 2.3 Label Recomm endations

2.3.1 Recommendations from Residue Reviews

Two change s are recommended for th e proposed supplemental Onager® Miticide label
for sugar beet

.

 A 120

- day P BI for rotational crops should be added to the label.

 The PHI should be changed from 21 days to 38 days.

These changes should be included in a revised supplemental label.

2.3.2 Recommendations from Occupational Assessment

No label changes are required based on the occupational assessment.

2.3.3 Recommendati ons f rom Residential Assessment

No label changes are required based on the residential assessment.

3.0 Introduction

3.1 Chemical Identity

Hexythiazox, trans

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxothiazolidine

- 3

- carboxamide, is an ovicide/miticide used to control mites on a variety of crops and in outdoor residential settings . Hexythiazox is a contact pesticide which achieves control of eggs or immature mites via direct contact or contact with treated surfaces.

The chemical str ucture and nomenclature of hexythiazox and its common moiety, PT

- 1

- 3 is shown in Table 3.1. The physicochemical properties of the technical grade hexythiazox are presented in Table 3.2.Hexythiazox Human Health Risk Assessment D313192

Page 8 of 32 T able 3. 1. Nomenclature of Hexythiazox.
Compound

Common name Hexythiazox
Company experimental names DPX

- Y5893, NA

- 73

IUPAC name (4 RS ,5 RS )

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 1,3

- thiazolidine

- 3

- carboxamide

CAS name trans

- 5

- (4

- chlorophenyl)

- N

- cyclohexyl

- 4

- methyl

- 2

- oxo

- 3

- thiazolidinecarboxamide

CAS # 78587

- 05

- 0

End

- use product/EP 1 lb/gal EC (EPA Reg. No. 10163

- 277; Onager® Ovicide/Miticide)

Compound

(4

- chlorophenyl)

- 4

- methyl

- 2

-

oxo

- 3

- thiazolidine moiety

Common name PT

- 1

- 3 moiety

Chemical name 5

- (4

- chlorophenyl)

- 4

- methyl

- thiazolidin

- 2

- one

3.2 Physical/Chemical Characteristics

Table 3.2. Physicochemical Properties of Hexythiazox.

Parameter Value Reference

Melting point/range 108.0

- 108.5 °C 00143533

pH Not applicable
Density 1.289 at 25 °C 00143533
Water solubility 0.12 ppm 44006301
Solvent solubility g/L
chloroform 1379 xylene 362

acetone 160.0
acetonitrile 28.6

n

- hexane 3.9
methanol 20.6 00143533

Vapor pressure <10

- 8 mm Hg at 25 oC 44006301
Dissociation constant, pK
a Not applicable
Octanol/water partition coefficient Log(P OW ) 560 (average) 0143533, 00146531

UV/visible absorption spectrum (molecular absorption coefficients) Maximum at 223 nm in acetonitrile, no absorption in the visible range. Not availableHexythiazox Human Health Risk Assessment D313192

Page 9 of 32 3.3 Pesticide Use Pattern Residue Chemistry Summary Document, D404573, D. Davis, 5/3/13

Gowan Company has submitted a supplemental label for Onager® Miticide (EPA Reg

No. 10163

- 277) which includes proposed regionally restricted use directions for sugar beets . The newly proposed use pattern for sugar beet is summarized in T able 3.3

.

Table 3 .3 . Summary of Proposed Directions for Use of Hexythiazox.

Application
Method Formulation

[EPA Reg. No.] Application

Rate (lb ai/A) Max. No.

Applic ation per Season Max.

Seasonal Application

Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Sugar Beet

Aerial, ground, or chemigation applications Onager®

Miticide [ 10163

- 277 ] 0.078

- 0.188 1 0.18 8 21 Restricted to use in Regions 11 and 12

. Idaho may treat a maximum of 134,000 acres of sugar
beets and 25,125 lbs. ai. Oregon may treat 9, 300
acres of sugar beets and 1,743.75 lbs. ai. Both states may use AI until September 31, 2014.

The following changes should be made to the supplemental label for sugar beet:

 A 120

- day PBI for rotational crops is needed

.

 The PHI should be changed from 21 days to 38 days.

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed new use of hexythiazox. Humans may be exposed to hexythiazox in food and drinking water, since hexythiazox may be applied directly to growing crops and appl ication may result in hexythiazox reaching surface and ground water sources of drinking water. Additionally humans may be exposed to hexythiazox in residential settings, since it may be applied to ornamental plantings in residences, public areas, and

recr eational sides, as well as on lawns and turf and to residential berries and fruit and nut trees. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post

application exposure for workers re

- entering treated fields.

Risk assessments have been previously prepared for the existing uses of hexythiazox. This risk assessment considers all of the aforementioned exposure pathways based on the proposed new use of hexythiazox, as well as the existing uses.

3.5 Consideration of Environmental JusticeHexythiazox Human Health Risk Assessment D313192

Page 10 of 32 Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. E xecutive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

. As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on
pat terns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumpti on patterns are compiled by the U.S. Department of Agriculture’s National

Healt h and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA ) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and catego rized by subgroups based on age
and ethnic group. Additio nally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associ ated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

4.1 Hazard Characterization

The toxicity datab ase for hexythiazox is complete and adequate for assessing risk

. The Hazard and Science Policy Council (HASPOC) concluded that an acute neurotoxicity study is not required at this time, and a new subchronic neurotoxicity study is not required, since the 28

- day neurotoxicity study is sufficient to assess subchronic

neurotox icity from hexythiazox exposure. The HASPOC also considered if an inhalation study was required for hexythiazox. B ased on a weight of evidence ( WOE) approach, the

H ASPOC concluded that a 28

- day inhalation toxicity study is not required for hexythiazox at this time. Th e committee’s deliberations considered all of the available hazard and exposure information for hexythiazox , as well as the following factors : (1) the

p hysical/chemical properties and low volatility (1.0x10

- 8 mm Hg @ 25°C) of hexythiazox; (2) the low acute inhala tion toxicity of hexythiazox; (3 ) the primary target organ of hexythi a zox toxicity is the liver and adrenal glands following repeated hexythi azox exposure; and (4 ) the use of an oral POD results in occupational inhalation MOEs greater than 1,400 ( HASPOC Memo, TXR No. 0056434, 9/18/12 )

.

Hexythiazox is associated with toxicity of the liver and adrenals following subchronic and chronic exposure to dogs, rats and mice, with the dog bei ng the most sensitive species. The prenatal developmental studies in rabbits and rats and the two

- generationHexythiazox Human Health Risk Assessment D313192

Page 11 of 32 reproduction study in rats showed no indication of increased susceptibility to in utero and/or postnatal expo sure to hexythiazox. Reproductive toxicity was not observed. There is no concern for neurotoxicity following exposure to hexythiazox. The toxicology database for hexythiazox does not show any evidence of treatment

- related effects on the immune system. Hex ythiazox is classified as “likely to be carcinogenic to humans”; however, s ince the effects seen in the study that serves as the basis for the chronic RfD occurred at doses substantially below the lowest dose that induced tumors, HED concluded that quantification of risk using a non

- linear approach; i.e., RfD, for hexythiazox will adequately account for all chronic effects , including carcinogenicity, that could result from exposure to hexythiazox.

4.2 Hazard Profile

The hazard profiles for hexythiazox are contained in Appendix A of this memorandum.

4.3 Dose

- Response Assessment/Endpoint Selection

No endpoint attributable to a single exposure was identified from the available oral toxicity database; therefore, an acute dietary r isk assessment for hexythiazox is not required.

The chronic dietary endpoint was selected from a one

- year toxicity feeding study in the dog with a NOAEL of 2.5 mg/kg/day. At the study LOAEL of 12.5 mg/kg/day,
increased absolute and relative adrenal wei ghts and associated adrenal histopathology were observed. A 100X uncertainty factor was applied to account for inter

- and intra

species variability resulting in a chronic reference dose (cRfD) of 0.025 mg/kg/day. Since the FQPA factor is reduced to 1X, t he RfD is equivalent to the chronic population adjusted dose (cPAD).

Short

- term and intermediate

- term incidental oral and inhalation endpoints for risk
assessment were selected from a two

- generation reproduction study conducted in the rat
with a NOAEL of 30 mg/kg/day. At the study LOAEL of 180 mg/kg/day, decreased pup body weight during lactation and delayed hair growth and/or eye opening, and decreased parental body

- weight gain and increased absolute and relative liver, kidney, and adrenal weights were o bserved. In a co

- critical subchronic toxicity study in rats, increased liver and adrenal weights, as well as adrenal histopathology (fatty degeneration of the adrenal zona fasciculata), were observed. Inhalation hazard is assumed to be equivalent to oral
hazard.

For the short

- term and intermediate

- term dermal risk assessment s , no quantification of risk is required, based on the fact that the dermal equivalent dose for this dermal exposure
scenario is 1.5

- fold greater than the limit dose considering the NOAEL of 30 mg/kg/day
from the oral reproduction study, and the estimated 2% dermal absorption for this compound

.Hexythiazox Human Health Risk Assessment D313192

Page 12 of 32 EPA has classified hexythiazox as “likely to be carcinogenic to humans” based upon increased incidences of malignant and combined benign/malignant liver tumors in high

dose female B6C3F1 mice, and benign mammary gland tumors, observed in high dose male rats. There was no evidence of carcinogenicity in male mice and female rats. EPA
concluded that the evidence as a whole was not str ong enough to warrant quantitative estimation of carcinogenic risk to humans using a cancer slope factor. HED concluded that quantification of risk using a non

- linear approach; i.e., RfD, for hexythiazox will adequately account for all chronic toxicity, i ncluding carcinogenicity that could result from exposure to hexythiazox. That conclusion is based on the following considerations: (1) the liver tumors found in the female mouse are common tumors; (2) the male mammary tumors were benign and of no biologica l significance; (3) hexythiazox is not mutagenic; (4) no carcinogenic response was seen in male mice or female rats

.

4 .4 FQPA Considerations

The Agency has determined that it is appropriate to reduce the FQPA safety factor to 1X for the following reasons:

 The toxici ty database for hexythiazox is complete.

 There is no evidence of increased susceptibility or sensitivity in rats or rabbits to

pre

- and/or post

- natal exposure to hexythiazox.

 There is no evidence of neurotoxicity in the database. A d evelopmental neurotoxicity (DNT) study is not required.

 The dietary risk assessment is highly conservative and not expected to
underestimate risk.

4.5 Summary of Toxicological Doses and Endpoints for Use in Human Risk
Assessments and Levels

Table 4.5.1. Toxicological Doses and Endpoints for Hexythiazox for Use in Dietary and Non

Occupational Human Health Risk Assessments 1

Exposure/
Scenario Point of

Departure Uncertainty

/FQPA Safety

Factors RfD, PAD, Level

of Concern for
Risk Assessment Study and Toxicological Effects

Acute Dietary All Populations No risk is expected from this exposure scenario as no hazard was identified in any toxicity study for

this duration of exposure

Chronic Dietary All Populations NOAEL=2.5

mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Chronic RfD = 0.025

mg/kg/day

cPAD = 0.025 mg/kg/day One

- Year Toxicity Feeding Study

- Dog

LOAEL = 12.5 mg/kg/day based on
increased absolute and relative adrenal weights and associated adrenal histopathology.Hexythiazox Human Health Risk Assessment D313192

Page 13 of 32 Table 4.5.1. Toxicological Doses and Endpoints for Hexythiazox for Use in Dietary and Non

Occupational Human Health Risk Assessments 1

Exposure/
Scenario Point of

Departure Uncertainty

/FQPA Safety

Factors RfD, PAD, Level

of Concern for
Risk Assessment Study and Toxicological Effects

Short

- and
Intermediate

Term
Incidental oral NOAEL=30

mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Residential LOC for

MOE = 100 2

- Generation Reproduction Study

– Rat

LOAEL = 180 mg/kg/day, based on decreased pup body weight during lactation and delayed hair growth and/or eye opening, and decreased parental body

- weight gain and increased absolute and relative liver, kidney, and adrenal weights

.

Co

- Critical
13

- Week Oral Toxicity Study

– Rat NOAEL = 5.5 mg/kg/day LOAEL = 38 mg/kg/day, based on
increased absolute and r elative liver weights in both sexes, increased relative ovarian and kidney weights, and fatty degeneration of the adrenal
zona fasciculata.

@ 397.5/257.6 mg/kg/day, decreased body

- weight gain in females, slight swelling of hepatocytes in central zone (bo th sexes), increased incidence of glomerulonephrosis in males, increased adrenal weights

Cancer (oral, dermal, inhalation) Classification: “Likely to be Carcinogenic to Humans”. Insufficient evidence to warrant a

quantitative estimation of human risk using a cancer slope factor based on the common liver tumors (benign and malignant) observed only in high dose female mice, and benign mammary gland tumors of no biological significance, observed only in h igh dose male rats in the absence of mutagenic concerns. The chronic RfD is protective of all chronic effects including potential carcinogenicity of hexythiazox.

1 Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no
obs erved adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (intraspecies). UF H = potential variation in sensitivity among members of the human population (interspecies). UF L = use of a LOAEL to extrapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Hexythiazox Human Health Risk Assessment D313192

Page 14 of 32 Table 4.5.2 Summary of Toxicological Doses and Endpoints for Hexythiazox for Use in Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of

Concern for
Risk
Assessment Study and Toxicological

Effects

Dermal
S hort

- and
intermediate

- Term N/A N / A N/A No dermal hazard identified

Inhalation
Short

- and
Intermediate

- Term Oral NOAEL = 30

mg/kg/day

Inhalation hazard
assumed to be equivalent to oral
hazard UF A =10x

UF H =10x Residential

LOC for MOE
= 100

Occupational
LOC for MOE
= 100 2

- Generation Reproduction Study

–

Rat

LOAEL = 180 mg/kg/day, based on decreased pup body weight during lactation and delayed hair growth and/or eye opening, and decreased parental body

- weight gain and increased absolute and relative liver,

k idney, and adrenal weights

Co

- critical
13

- Week Feeding Study

– Rat LOAEL = 38.1 mg/kg/day, based on
increased absolute and relative liver weights in both sexes, increased relative ovarian and kidney weights, and fatty degeneration of the
adrenal zona fasc iculate.

Cancer (oral, dermal, inhalation) Classification: “Likely to be Carcinogenic to Humans”. ”. Insufficient evidence to warrant a

quantitative estimation of human risk using a cancer slope factor based on the common liver tumors (benign and malignant) observed only in high dose female mice, and benign mammary gland tumors of no biological significance, observed only in h igh dose male rats in the absence of mutagenic concerns. The chronic RfD is protective of all chronic effects including potential carcinogenicity of hexythiazox.

1 Point of Departure (PoD) = A data point or an estimated point that is derived from observ ed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no
observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertai nty factor. UF A = extrapolation from animal to human (intraspecies). UF H = potential variation in sensitivity among members of the human population (interspecies). UF L = use of a LOAEL to extrapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = popula tion adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

5 .0 Dietary Exposure/Risk Characterization

5.1 Residue Chemistry Summary Reside Chemistry Summary, D404573, D. Davis, 5/3/13

The nature of the residue in plants, animals, and water has been adequately delineated.
The residue s of concern for the tolerance e xpression and risk assessment are the parent compound and its metabolites which contain the (4

- chlorophenyl)

- 4

- methyl

- 2

- oxo

- 3

- thiazolidine moiety

.

Three f ield trial s divided among regions 10 and 11 had hexythiazox residues in/on sugar
beet roots that ranged from 0.0 21

- 0. 053 ppm , based on a 45

- day PHI and an applicationHexythiazox Human Health Risk Assessment D313192

Page 15 of 32 rate of 0.187 lb ai/A

. Although residue data were also provided for sugar beet tops, HED notes that this commodity is no longer considered a significant livestock feedstuff ( Table 1 Feedstuffs (June 2008)). Thus, no toleran ce or residue review is needed for sugar beet
tops. O ne decline study showed residues over a PHI range of 38

- 66 days ; residues were relatively constant over this range

. Thus, these data support a minimum PHI of 38 days
and the label should be modified to reflect this. Hexythiazox residues were stable at

- 10°C for up to 7 months in radish roots (D247631/D260343, G.Kramer, 3/20/2000) ; th ese data can be translated to sugar beet roots

. Field trial residue data and storage stability conditions are presented in Appendix C: Field Trial Residue Data.

Processed commodities of sugar beets include refined sugar, dried pulp, and molasses. No processing studies were submitted to support this se ction 18 request

. F or Section 3 registration of this use, processing factor studies will be required. Dietary burden including sugar beet feedstuffs was calculated assum ing maximum theoretical
concentration factor s of 20x for molasses and dried pulp

. The inclusion of sugar beet did not increase livestock dietary burden s. As a result, current livestock tolerance levels are adequate (D404573/ D410813, D. Davis, 05/013). In consideration of the available confined and field rotational crop studies, a 120

- day p lant back interval (PBI) for all crops not listed on the label is appropriate ; the proposed label should be modified to
reflect this PBI

.

5.2 Drinking Water Residue Profile

EFED Drinking Water Assessment, D401798, A. Shelby, 6/21/12 EFED Drinking Water Assessment, D404203, A. Shelby, 1/17/12

Currently, the Agency does not have drinking water monitoring data for hexythiazox. Therefore, the potential for hexythiazox residues in drinking water was evaluated through modeling. No new drinking water assessm ent was required for this section 18 action.

Surface water residues are expected to exceed ground water residues; therefore, EFED provided estimated drinking water concentrations (EDWCs) for various scenarios from
the Tier II PRZM/EXAMS surface water model assuming a 0.95 percent cropped area ( PCA ) adjustment. T he maximum estimated surface water concentrations for total residues of hexythiazox were f rom the MS soybean scenario. The 1

- in

- 10 year annual average value of 4.31 ppb from this scenario was u sed in the chronic dietary risk

assessment which is protective of the new (revised using 0.87 PCA) 1

- in

- 10 year annual average of 3.9 ppb (Appendix F)

.

5.3 Dietary Exposure and Risk Dietary Exposure and Risk Memorandum

, D 404574 , D. D avis, 5/3/13

No new dietary exposure analyses were required for this section 18 action. The addition of sugar beets to the most recent dietary exposure analysis did not change the r isk
estimates.

5 .3.1 Acute Dietary Exposure/RiskHexythiazox Human Health Risk Assessment D313192

Page 16 of 32 No toxic effects attributable to a si ngle dose of hexythiazox were observed in the toxicology database; therefore, an acute dietary exposure and risk assessment for this
chemical was not conducted.

5 .3.2 Chronic Dietary Exposure/Risk

The chronic dietary risk assessment used tolerance level residues, included modeled drinking water estimates, assumed 100% crop treated, and incorporated DEEM default

proc essing factors. The dietary assessment could be substantially refined using anticipated residues, percent crop treated information and empirical processing data;
however these refinements were not conducted since risk estimates were not of concern.
This highly conservative risk assessment showed no risks of concern (<100% of the chronic popu lation adjusted dose (cPAD)) for the U.S. General P opulation or any subpopulation. The estimated exposure to the U.S. General P opulation res ulted in a risk equivalent to 17 % of the c PAD. The estimated exposure to children 1

– 2 years of age, the most hig hly exposed subpopulation, res ulted in a risk equivalent to 82 % of the cPAD. Results for all subpopulat ions are summarized in Table 5 .3 .3, below.

5 .3.3 Cancer Dietary Risk

The HED Cancer Assessment Review Committee (CARC) has recently reconsidered hexythiazox and has classified the chemical as “Likely to be Carcinogenic to Humans”, but has determined that there is insufficient evidence to quantify risk using a cancer slope

f actor. Rather, the committee concluded that regulation based on the chronic reference
dose will be protective for both chronic and carcinogenic risks. As noted above there are
no chronic risks of concern.

Table 5.3.3. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Hexythiazox

Population Subgroup Chronic Dietary Cancer

Dietary Exposure (mg/kg/day) % cPAD* Dietary Exposure (mg/kg/day) Risk

General U.S. Population 0.004356 17 No concern for risks associated with
the carcinogenic potential of hexythiazox.

All Infants (< 1 year old) 0.008040 32

N/A N/A Children 1

- 2 years old 0.020483 82

Children 3

- 5 years old 0.013364 54

Children 6

- 12 years old 0.006416 26

Youth 13

- 19 years old 0.003220 13

Adults 20

- 49 years old 0.002878 12Hexythiazox Human Health Risk Assessment D313192

Page 17 of 32 Table 5.3.3. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Hexythiazox

Population Subgroup Chronic Dietary Cancer

Dietary Exposure (mg/kg/day) % cPAD* Dietary Exposure (mg/kg/day) Risk

Adults 50+ years old 0.003229 13

Females 13

- 49 years old 0.003068 12

* Most highly exposed subpopulation is highlighted in bold.

5 .4 Anticipated Residue and Percent Crop Treated (%CT) Information

Anticipated residues and percent crop treated information were not used in the dietary exposure and risk assessment

.

6.0 Residential and Other Non

- Occupational Exposures/Risks Occupational and Residential Exposure and Risk Assessment, D404018, A. LaMay, 5/6/13 Occupational and Residential Exposure and Risk Assessment, D396864, A. LaMay, 9/25/12

There are no new residential uses proposed with this action; however, there are registered
uses on residential sites which have been previously assessed , including (1) ornamental
lan dscape plantings in residences, public areas, and recreational sites such as campgrounds, golf courses, parks and athletic fields, (2) ornamental lawns and turf (including residential), (3) residential pome fruit, stone fruit, and nut trees, and residentia l
caneberries.

6.1 Residential Handler Exposure and Risk

Since hexythiazox does not pose a dermal risk, only inhalation exposure assessments were conducted for residential handlers. Residential handler exposure is expected to be
short

- term in duration . Intermediate

- term exposures are not likely because of the intermittent nature of applications by residential applicators. Residential handler inhalation margins of exposure (MOEs) significantly exceed 100 for all scenarios
assessed and are not of conce rn. Residential handler MOEs range from 420,000 to 330,000,000.

6.2 Residential Post

- application Exposure

There is the potential for post

- application exposure for individuals exposed as a result of being in an environment that has been previously treate d with hexythiazox. The quantitative exposure/risk assessment for residential post

- application exposures is based on incidental oral exposure to treated turf. As no dermal hazard was identified, a quantitative dermal post

- application assessment is not re quired. Short

- term exposure durations are anticipated for incidental oral exposures due to the intermittent nature of applications in residential environments. As the aerobic soil metabolism half life forHexythiazox Human Health Risk Assessment D313192

Page 18 of 32 hexythiazox is 145.2 days 1 , intermediate

- term exp osure is also possible for incidental soil ingestion exposure.

Child incidental oral exposure to treated turf was assessed for hexythiazox. Risk estimates greatly exceed the LOC of 100 for all scenarios associated with children’s exposure to treated tu rf and are not of concern. The short

- term hand

- to

- mouth MOE for children is 11,000; the short

- term object

- to

- mouth MOE for children is 350,000; and the
short

- and intermediate

- term incidental soil ingestion MOE for children is 4,700,000.
In accordance wi th 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post

- application exposure to turf. In the absence of chemical

- specific TTR data,

EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of all TTR data, available at the time, which resulted in the selection of revised liquid and granular default values for the
fractio n of the application rate available for transfer after a turf application (F AR ). These values are based on an analysis of 59 TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granules, and 12 studies using granules). The liquid results (N=131 ) indicate a range of F AR values from 0.0005% to 6.1% and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a large range of transferability is observed and this variability can potentially be
attribu table to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR values is not expected when considering TTR data for a single chemical. HED selected 1% and 0.2% as high

end default values for liquid and granular products, respectively. Although there may be a small degree of uncertainty in the use of the default TTR value for hex ythiazox (i.e.,
there is a small chance that the F AR value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s residential postapplication turf assessment methodology will more than compensate for this potent ial uncertainty (i.e., the methodology is likely to overestimate exposure by a factor greater than the factor than the highest measured F AR values exceed the defaults ). For example, when assessing residential post

- application turf exposure, EPA assumes the following: exposures occur

to zero

- day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, the grass is not mowed, etc); individuals perform t he same postapplication activities performed in the turf transfer coefficient study day after day (e.g., tumbling, playing on turf with toys, etc.); and individuals engage in these post

- application activities for a high

end amount of time every day that i s represented by data reflecting time children spend outdoors and not specifically engaged in activities on turf, when in actuality children do not spend all of their outdoor time on turf and high

- end levels of activity will not occur every day.

1 Hexythiazox: Drinking Water Assessment for New Use on wheat, alfalfa, timothy, eggplant and peppers

. Andrew Shelby. DP Barcode: 396529 & 401798. 6/21/2012

.Hexythiazox Human Health Risk Assessment D313192

Page 19 of 32 Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the estimated residential turf post

- application exposure for residential turf using default TTR values for hexythiazox is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 10 times higher than the level of concern, MOE = 11,000 compared to the LOC of 100 ); EPA is waiving the 40CFR TTR data requirement. In this instance, it is unlikely that chemical

- specific TTR data would be needed to further refine exposure assessments or would add appreciably to our general understanding of the availability o f turf transferable pesticide residues.

6.3 Other

6.3.1. Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., ground
boom and air blast) employed for hexythiazox

. The agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data Call

- In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other pa rties to develop the best spray drift management practices (see the agency’s Spray Drift website for more information). 2 The agency has also developed a policy on how to appropriately consider spray drift as a potential source of exposure in risk assessm ents for pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the r evised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift.
This document outlines the quantification of indirect non

- occupatio nal exposure to drift.
It is noted that the 0.19 lb ai/acre application rate for turf was modeled to estimate post

application residential exposure of children. As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any exposure of children via spray drift from agricultural hexythiazox applications.

6.3.2. Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and re ceived the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htmHexythiazox Human Health Risk Assessment D313192

Page 20 of 32 evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is requir ed
for hexythiazox

.

7.0 Aggregate Risk Assessments and Risk Characterization

7.1 Acute Aggregate Risk

No toxic effects attributable to a single dose of hexythiazox were observed in the toxicology database; therefore, an acute aggregate risk assessment for this chemical is not required.

7.2 Short

- and Intermediate

- Term Aggregate Risks

The short

- and i ntermediate

- term aggregate risks combine residential handler (adult only) and post application exposures with average food and water exposures.

Short

- and intermediate

- term aggregate margins of exposure for adults and children greatly exceed the LOC of 100 and are not of concern. Short

- and intermediate

- term estimated exposures and risks are shown in Table 7 .2 , below.

Table 7.2 Short

- Term and/or Intermediate

- Term Aggregate Risk Calculations

Population Short

- Term Scenario

NOAEL mg/kg/day LOC 1 Max
Allowable Exposure 2 mg/kg/day Average

Food & Water Exposure mg/kg/day Residential

Exposure 3 mg/kg/day Aggregate

MOE (food and residential) 4

Adult Male 30 100 0.3 0.003229 0.000072 9,100

Adult Female 30 100 0.3 0.003068 0.000072 9,600

Child 30 100 0.3 0.020483 0.0029 1,300

Intermediate

- Term Scenario

Adult Male 30 100 0.3 0.003229 N/A 9,300

Adult Female 30 100 0.3 0.003068 N/A 9,800

Child 30 100 0.3 0.020483 0.0000063 1,500

1 The LOC of 100 is based on the standard inter

- and intra

- species extrapolation factors.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC = 30/100 = 0.3 mg/kg/day.

3 Residential Exposure values taken from a previous r esidential assessment (D.Davis, 5/6/2013).

4 Aggregate MOE = [NOAEL  (Avg Food & Water Exposure + Residential Exposure)]

7.3 Long

- Term (Chronic) Aggregate RiskHexythiazox Human Health Risk Assessment D313192

Page 21 of 32 As there are no uses that are expected to result in long

- term residential exposure, long

term (chronic) aggregate risk includes only dietary (food and water) exposure. As noted
in Section 5.3.2 of this memorandum, there is no chronic dietary risk of conce rn.

8.0 Cumulative Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to hexythiazox and any other substances and hexythiazox does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that hexythiazox has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s

website at http://w ww.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposures and Risks Occupational and Residential Exposure and Risk Assessment, D404018, A. LaMay, 5/6/13

9.1 Occupational Handler Risk

The occupational exposure and risk assessment addresses risks to workers exposed in an occupational setting via the dermal and inhalation routes of exposure. However, for hexythiazox a quantitative dermal risk assessment is not required; therefore risks w ere quantitatively assessed for inhalation exposure only. Based on the proposed uses, short

term exposures are anticipated as the proposed uses indicate the product is only to be applied once per year. As the inhalation point of departure is the same for both short

- and
intermediate

- term exposure durations, the short

- term assessment is protective of possible longer

- term exposures (i.e., commercial applicators that may apply a product over a period of weeks).

The proposed Section 18 use is for sugar beets with an application rate of 0.1875 lb ai/acre. The applicable occupational handler scenarios for sugar beets have been previously assessed at the same rate for other agricultural crops. This includes application of the emulsifiable concentrate at 0.1875 lb ai/acre to field crops via aerial, chemigation and ground boom equipment. All occupational handlers scenarios resulted in estimated inhalation margins of exposure (MOEs) which were significantly greater than 100 with baseline inhalation protection (no respirator). Therefore, inhalation risks are not of concern and inhalation personal protective equipment (PPE, i.e., respirators) is not required.

9.2 Occupational Post Application RiskHexythiazox Human Health Risk Assessment D313192

Page 22 of 32 HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred

to as re

- entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activi ties related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide applicat ion, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

There are multiple potential sources of post

- application i nhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and re

- suspension of dusts and/or particulates that contain pesticides. The agency sought e xpert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov /scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for hexythiazox

.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the agency's risk

assessments.

Although a qu antitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely t o result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide applicatio ns)].

As no dermal hazard has been identified for hexythiazox, quantification of dermal post

application risk is not required. In accordance with the updated Part 158 data requirements (2007), one or more dislodgeable foliar residue (DFR) studies are req uiredHexythiazox Human Health Risk Assessment D313192

Page 23 of 32 when a pesticide has residential or occupational uses that could result in post

- application dermal exposure. However, as quantification of dermal risk is not required for hexythiazox, a DFR study is not required for hexythiazox at this time.

The RE I specified on the proposed label is based on the acute toxicity of hexythiazox. Hexythiazox is classified as Toxicity Category IV for acute dermal toxicity, Toxicity Category IV for acute dermal irritation, and Toxicity Category III for eye irritation. It is
not a skin sensitizer. Under WPS for agricultural pesticides, active ingredient ’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned

a 12

- hour REI. Therefore, the WPS interim REI of 12 hours is a dequate to protect agricultural workers from post

- application exposures to hexythiazox.

10.0 Human Stu dies

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) database; the ARTF database; and the Residential SOPs, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have rece ived that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found a t the Agency website 3

.

3 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticid es/science/post

- app

- exposure

- data.htmlHexythiazox Human Health Risk Assessment D313192

Page 24 of 32 Appendix A. Toxicology Assessment

A.1 Toxicity Profiles

Table A.1.1. Acute Toxicity Data on Hexythiazox Technical
Guideline No./ Study Type MRID No. Results Toxicity Category

870.1100 Acute oral toxicity 00146549 LD 50 = >5000 mg/kg IV

870.1200 Acute dermal toxicity 00146550 LD 50 = >5000 mg/kg IV

870.1300 Acute inhalation toxicity 00146554 LC 50 = >2.0 mg/L IV

870.2400 Primary eye irritation 00146551 Reddened conjunctiva III

870.2500 Acute dermal irritation 00146552 Non irritant IV

870.2600 Skin sensitization 00146553 Non sensitizer N/A

Table A.1.2. Toxicity Profile of Hexythiazox

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100
90

- Day oral toxicity rat 45067101 (1983) Acceptable/guideline 0, 10, 70, 500, or 3500

ppm M: 0, 1.2, 8.1, 58.6, or 397.5 mg/kg/day F: 0, 0.8, 5.4, 38.1 or 257.6 mg/kg/day NOAEL = 8.1/5.4 mg/kg/day, males/females LOAEL = 58.6/38.1 mg/kg/day, males/females, based on increased absolute and relative liver weights in both sexes, increased relative ovarian and kidney weights, and fatty degeneration of the adrenal zona fasciculata.

@ 397.5/257.6 mg/kg/day , decreased body

- weight gain in females, slight swelling of hepatocytes in central zone (both sexes), increased incidence of glomerulonephrosis in males, increased adrenal weights

870.3700a Prenatal developmental toxicity rat 44955711 (1984) Acceptable/guideline 0, 240, 720, or 2160 mg/kg/day Maternal NOAEL = 240 mg/kg/day LOAEL = 720 mg/kg/day based on decreased maternal body weight gain, and decreased food consumption. Developmental NOAEL = 240 mg/kg/day LOAEL = 720 mg/kg/day based on delayed ossification.

870.3700b Prenatal developmental toxicity rabbit 00146555 (1984) Acceptable/guideline 0, 120, 360, or 1080 mg/kg/day Materna l NOAEL  1080 mg/kg/day LOAEL >1080 mg/kg/day Developmenta l NOAEL  1080 mg/kg/day LOAEL >1080 mg/kg/day

870.3800

Two

- Generation reproduction and fertility effects rat 00147578 (1985) Acceptable/guideline 0, 60, 400, or 2400 ppm Average doses across generations: M: 0, 4.45, 29.73, or 180.67 mg/kg/day F: 0, 5.27, 34.77, or 207.67 mg/kg/day Parental/Systemic NOAEL = 29.73/34.77 mg/kg/day,
males/females LOAEL = 180.67/207.67 mg/kg/day, males/females, based on decreased body weight gain and increased absolute and relative liver, kidney, and adrenal weights. Reproductive NOAEL  180.67/207.67 mg/ kg/day,
males/females LOAEL >180.67/207.67 mg/kg/day, males/females Offspring NOAEL = 29.73/34.77 mg/kg/day, males/females LOAEL = 180.67/207.67 mg/kg/day, males/females, basedHexythiazox Human Health Risk Assessment D313192

Page 25 of 32 Table A.1.2. Toxicity Profile of Hexythiazox

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

on decreased pup body weight during lactation, and delayed hair growth and/or e ye opening

.

870.4100b Chronic toxicity dog 00151359, 00146556, 00156895 (1984) Acceptable 0, 100, 500, or 5000 ppm (0, 2.5, 12.5, or 125 mg/kg/day) M: 0, 2.87, 13.1, or 153 mg/kg/day F: 0, 3.17, 13.9, or 148 mg/kg/day

4

- week: 0, 125, 500, 2000, 8000 ppm NOAEL = 2.5 mg/kg/day LOAEL = 12.5 mg/kg/day based on increased absolute and relative adrenal weights and associated adrenal histopathology (adrenal cortex hypertrophy).
@ 125 mg/kg/day, relative adrenal weights and associated adrenal cortex hypertrop hy (more pronounced)

4

- week range

- finding: relative adrenal weight increased at 2000 ppm (50 mg/kg/day) and 8000 ppm (200 mg/kg/day)

870.4300 Chronic Toxicity/ Carcinogenicity rat 00146559 (1984) Acceptable/guideline 0, 60, 430, or 3,000 ppm M: 0, 3, 23, or 163 mg/kg/day F: 0, 4, 29, or 207 mg/kg/day NOAEL = 23/29 mg/kg/day, males/females LOAEL =163/207 mg/kg/day, males/females based on decreased body weight and body weight gain and increased absolute and relative liver weights in both sexes.

No evi dence of carcinogenicity

870.4300 Carcinogenicity mice 00147577, 00156896 (1985) Acceptable/guideline 0, 40, 250, or 1500 ppm M: 0, 6.72, 41.6, or 267 mg/kg/day F: 0, 8.38, 51.2, or 318 mg/kg/day NOAEL = 41.6/51.2 mg/kg/day, males/females
LOAEL = 267/318 mg/kg/day, males/females) based on decreased male body weight and body weight gain, and increased absolute and relative liver weights in both sexes.

Evidence of carcinogenicity (causes liver tumors in females).

Gene Mutation
870.5100 (Salmonella typhimurium and
Escherichia coli reverse gene mutation assay) 44955710 (1983) Acceptable The test was negative up to the highest dose tested (6400 μg/plate +/

- S9.

Gene Mutation

870.5300 ( In vitro mammalian cell forward gene mutation assay in CHO cells) 00155154 (1985) Acceptable Independently performed trials were negative up to precipitating doses (  60 μg/mL) and severely cytotoxic concentrations (200 μg/mL

- S9; 400 μg/mL +S9).

Cytogenetics

870.5375

In vitro mammalian cell cytogenetic assay in
CHO cells 00156894 (1986) Acceptable The test was negative up to precipitating doses accompanied by severe cytotoxicity (  167 μg/mL +/

- S9).Hexythiazox Human Health Risk Assessment D313192

Page 26 of 32 Table A.1.2. Toxicity Profile of Hexythiazox

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

Cytogenetics
870.5395

In vivo mouse micronucleus assay 44955708 Unacceptable

There’s an update The results were inconclusive because a positive response, which was within the wide range of historical background data, was recorded for female mice at the mid

- and high

doses (500 and 1000 mg/kg). The assay shou ld be repeated to confirm or refute the equivocal results.

Other Effects

870.5550

In vitro UDS assay in primary rat hepatocytes 00156893 (1985) Acceptable The test was negative up to a lethal dose (250 μg/mL).

870.6200b
Subchronic neurotoxicity Crj:CD(SD)IGS(SPF)

rats 48657401 (2004) Acceptable/non

- guideline 0, 100, 1000, or 10000

ppm Males: 0, 8.8, 88.7, or 868.2 mg/kg/day Females: 0, 9.5, 90.1, or 892.7 mg/kg/day (28 days) NOAEL = 1000 ppm (males 88 mg/kg/day; females 90 mg/kg/day).

LOAEL = 10000 ppm (males 868 mg/kg/day; females 892 mg/kg/day), based on decreased motor activity in both sexes, decreased body weight in males, increased adrenal weight in females, and increased liver weight in both sexes.

HASPOC (D0056434): 28

- day duration i s sufficient to
assess sub

- chronic neurotoxicity from hexythiazox exposure

870.7485
Metabolism and pharmacokinetics 00146558 (1985) Acceptable/guideline

Single oral dose at 10 mg/kg (Group B); 14 daily oral doses (10 mg/kg) of unlabeled
material followed by one dose (10 mg/kg) of [ 14 C] test material (Group C); and a single oral dose of 880 mg/kg (Group D). Absorption and distribution of dosed radioactivity were rapid. The radioactive material was rapidly eliminated in the urine and feces; the ma

jority of the radioactivity was
eliminated within 24 hours. There were no observable
differences in the total elimination of NA

- 73 between male and female rats. The major route of elimination in both the male and female rats was by fecal excretion. The major metabolite found, PT

- 1

- 8 (cis), accounted for 8

- 12% of the administered radioactivity in the low dose groups. Approximately 11

- 20% and 65

- 69% of the dosed radioactivity was identified as unchanged NA

- 73 in the low

dose and high

- dose groups, respecti vely. All other metabolites were present at low concentrations (<2%). There was no apparent sex difference in metabolite formation. Significant levels of NA

- 73 equivalent [ 14 C]

- residues were detected in the fat, liver, and adrenals. A sex

related diffe rence in the residue levels of all tissues was observed, with residues in female tissues being two

- fold higher than those found in male tissues.

870.7485
Metabolism and pharmacokinetics 0146557 (1983) Acceptable/non

- guideline

Single low dose (10 mg/kg/day) Total recovery of radioactivity 72 hours after treatment
accounted for 101.9

- 103% of the dose. The distribution of radioactivity 72 hours after dosing was as follows: 1) 30% (male and female) was excreted in the urine, 2) 60% (female) to 67% (male) was ex creted in the feces, and 3) about 4% (male) to 10% (female) of the administered radioactivity remained in the tissues, with the highest concentration in the fat (2.3 ppm, males; 5.4 ppm, females). Significant sex differences existed for the pharmacokineti cs of NA

- 73 in these rats, with females exhibiting slower elimination rats and higher tissue residues (about double)Hexythiazox Human Health Risk Assessment D313192

Page 27 of 32 Table A.1.2. Toxicity Profile of Hexythiazox

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

than males. NA

- 73 was metabolized to a large number of
metabolites that were excreted both in the urine and feces.
Seven metabolites were structurally identified in addition to the parent compound in both excreta of both sexes, with the major fecal metabolite, PT

- 1

- 8 (cis) accounting for 10% of the dosed radioactivity. The others were all minor metabolites accounting for less than 1.4%. A bout 20% of the dose was excreted as unchanged NA

- 73 (97% of which was in the feces). No significant sex difference was apparent with respect to metabolite formation.

870.7600 Dermal penetration 40608402, 40787901 (1985) Unacceptable The total percent of dose absorbed averaged 2%, 1%, and 1.1% for cannulated rats (10

- hour sacrifice) and 0.8%, 0.2%,
and 0.2% for non

- cannulated rats (1

- hour sacrifice) at the low, medium, and high dose levels, respectively. The amount of radioactivity in the blood, carcass, urine and other organs totaled <2% of the applied dose. The results of this study (2% dermal absorption) can be used for risk

assessment purposes.

870.7800
Immunotoxicity 48685201 (2012)
Acceptable/Guideline Immunotoxicity NOAEL is 4 500 ppm (equivalent to 904 mg/kg/day). A LOAEL was not established.Hexythiazox Human Health Risk Assessment D313192

Page 28 of 32 Appendix B : Toxicology Data Requirements

The toxicology data requirements (40 CFR 158.340) for the food uses of hexythiazox are presented below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table B. Toxicology Data Requirements

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ..................... yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes

yes

yes

no CR yes

yes D

no C

no

no A

870.3700a Developmental Toxicity (rodent)

................................ ... 870.3700b Developmental Toxicity (nonrodent)

............................ 870.3800 Reproduction

................................ ................................ . yes

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ ................... 870.4300 Chronic/Oncogenicity

................................ ................... yes

yes

yes

yes

yes yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation

– bacterial

.................... 870.5375 Mutagenicity

— Structural Chromosomal Aberrations

... 870.5550 Mutagenicity

— Other Genotoxic Effects

....................... yes

yes

yes y es

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

............................... 870.6100b 90

- Day Neurotoxicity (hen)

................................ .......... 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Develop. Neurotoxicity

................................ ................. no

no

yes

yes CR -

-

no A

yes B

no

870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. yes

no

yes yes

yes

yes

Special Studies

A HASPOC (D0056434): not required at this time; B HASPOC (D0056434): 28

- day study is sufficient to assess subchronic neurotoxicity from hexythiazox exposure ; C dermal equivalent dose is 1.5

- fold greater than the limit dose considering the NOAEL of 30 mg/kg/day from the oral reproduction study and the estimated 2% dermal absorption for this compound ; D not required since there is a 4

- week study and a 1

- year study availableHexythiazox Human Health Risk Assessment D313192

Page 29 of 32 Appendix C: Field Trial Residue Data

Three trials were completed by Gowan Company in 2013 on sugar beets in regions 10
and 11. Onager® 1E Miticide was applied to the sugar beets at 0.1875 lb ai/A.

Residue Data from Sugar Beet Field Trials with Hexythiazox.

Location: State; Year (Trial ID ) Region Crop/ Variety Commodity

Type End

- Use

Product Rate

lbs ai/A (kg ai/ha) PHI

(days) Residues 1 (ppm)

Hexythiazox A verage

ID; 2013 (TCI

- 13

- 382

- 03) 11 Sugar Beet/
9120RR Sugar Beet

Root Onager®

1E 0.1868

(0.2094) 45 0.0229, <0.02 0.02145

CA; 2013 (TCI

- 13

- 382

- 04) 10 Sugar Beet/
Phoenix Sugar Beet

Root Onager®

1E 0.1848

(0.2071) 38 0.0493, 0.0580 0.05365

45 0.0597, 0.0455 0.0526

59 0.0528, 0.0635 0.05815

66 0.0453, 0.0469 0.0461

WA; 2013 (TCI

- 13

- 382

- 06) 11 Sugar Beet/ Hillesahog
9294RR Sugar Beet

Root Onager®

1E 0.1887

(0.2115) 45 0.0326, 0.0309 0.03175

0.9359 (1.049) 0.205, 0.213 0.209

1 Expressed as parent equivalents.

Summary of Residues from Sugar Beet Field Trials with Hexythiazox.

Crop
Matrix Analyte End Use

Product Total

Application

Rate
lbs ai/A (g ai/ha) PHI

(days) n Residues 1 (ppm)

Min. 2 Max. 2 LAFT 3 HAFT 3 Median 3 Mean 3 SD 3

Sugar Beet

Sugar

Beet

Root Hexythiazox Onager®

1E
Miticide 0.1875

(0.2102) 38 1 0.0493 0.0580 0.0537 0.0537 0.0537 0.0537

---

45 3 <LOQ 0.0597 0.02145 0.209 0.0422 0.0787 0.0878

59 1 0.0528 0.0635 0.0582 0.0582 0.0582 0.0582

--- 66 1 0.0453 0.0469 0.0461 0.0461 0.0461 0.0461

---
1 Expressed as parent equivalents.

2 Values based on total number of samples.

3 Values based on per

- trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = s tandard deviation.
n = number of field trials.

Rounded MRL was calculated using the OECD calculator. Each completed field trial average was included in the calculation. The rounded MRL was 0.15 ppm for sugar beet

roots.

Sugar beet storage stability information was not included in this study. Sugar beets and radishes are both a part of the vegetable, root

, and tuber, crop group 01

, so radish storage data ( D247631/D260343, G. Kramer, 3/20/2000) were translated to sugar beets

. The field residue samples were stored frozen for a maximum of 7 months

.

Summary of Storage Conditions.

Matrix (RAC) Storage Temperature (°C) Actual Storage Duration

( months ) Interval of Demonstrated Storage Stability (month )

Radish root

- 10°C 0

- 7 7Hexythiazox Human Health Risk Assessment D313192

Page 30 of 32 Appendix D: Maximum Residue Limits (MRL)

Table B1. Summary of US and International Tolerances and Maximum Residue Limits for Hexythiazox (128849) Residue Definition :
US Canada Mexico 2 Codex 3

40 CFR 180.448:

Plant: Compliance with the tolerance levels specified below is to be determined by measuring only hexythiazox and its metabolites containing the (4

- chlorophenyl)

- 4

- methyl

- 2

- oxo

- 3

- thiazolidine moiety,
calculated as the stoichiometric equivalent of hexythiazox. None Plant commodities: Hexythiazox
Animal commodities: Sum of hexythiazox and all
metaboli tes containing the

trans

- 5

- (4

- chlorophenyl)

- 4

- methyl

- 2

- oxothiazolidine

moiety (PT

- 1

- 3), expressed as hexythiazox
The residue is fat

- soluble

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex 3
Beet, Sugar, Root 0.15

Completed: M. Negussie; 07/24/14

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quan titation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have n ot been finalized by the
CCPR and the CAC.Hexythiazox Human Health Risk Assessment D313192

Page 31 of 32 Appendix E: OECD Calculator MRL Output

Hexythiazox

Sugar Beet Root

USA

0.1875 lbs ai/A PHI 45 days

Total number of data (n) 3
Percentage of censored data 0%

Number of non

- censored data 3

Lowest residue 0.021
Highest residue 0.053

Median residue 0.032

Mean 0.035
Standard deviation (SD) 0.016
Correction factor for censoring (CF) 1.000

Proposed MRL estimate

- Highest residue 0.053

- Mean + 4 SD 0.099

- CF x 3 Mean 0.106

Unrounded MRL 0.106

Rounded MRL 0.15

High uncertainty of MRL estimate.

[Small dataset]

Residues (mg/kg)

0.021

0.053

0.032Hexythiazox Human Health Risk Assessment D313192

Page 32 of 32 Appendix F: Estimated Drinking Water Concentration

Katelynn,

I’ve looked at the referenced assessments and it seems that I didn’t report the annual

averages. Sorry about that! I’ve attached the DWA that was referenced in the recent

assessments. The PRZM

- EXAMS output on page 10 shows a 1

- in

- 10 year annual

average of 4.5325 ppb. Multiply this concentration by the percent cropped area of 0.87 and the resulting EDWC is 3.9 ppb. 3.9 ppb should be used as the 1

- in

- 10 year annual

average.

Regards,



### A NDREW 

### S HELBY

PHYSICAL S CIENTIST U.S. EPA O FFICE OF P ESTICIDE P ROGRAMS
E NVIRONMENTAL F

ATE AND E

FFECTS D IVISION
P HONE : (703) 347

- 0119

From: King, Katelynn
Sent: Monday, August 11, 2014 9:50 AM

To: Shelby, Andrew Subject: Section 18 Importance: High

Hi Andrew,

I am also completing a section 18 risk assessment for hexythiazox on sugar beets. Could you please let me know if the EDWC is still 4.31 ppb for the 1

- in10 year annual average?
Thanks.

Katelynn King Biologist, EPA Office: (703) 347

- 0193 Mail Code: 750P, Arlington, VA