CLETH ODIM Hum a n H ea l th Risk Assessment DP No. D4 25763



### UNITED S TA TES ENV IRONMENTAL PROTECT I ON AGENCY

WASHINGTON

, D .C. 20460

MEMORANDUM

Date : Ap ri 1 1 8, 2016 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

SUBJECT: Clethod im. Human H eal th Aggregate Risk Assess m e nt fo r the Pro posed New Uses

o n S te v i a, Pome Fruit Group 11-10 , S ton e Fru i t Group 12-12, Bu l b Onion Subgroup 3

- 07 A, L ow G r ow in g Berry Subgroup l 3

- 07G, (excep t Cra nb e r ry); Rapeseed S ub gro up 20A (excep t Flax Seed), S unfl ower S ub group 208, Cottonseed S ub g r oup 20C, and Fruiting Vegetable Group 8-l 0.

PC Code: 121011 Deci s ion No.: 497978 Pet i tion No .: 4E8334 Risk As s e ss m e nt T y p e: Single Che in ica l / Aggrega t e Assessment DP Barcod e : 0425763 R egistrat ion Nos.: 59639

- 3, 59639- 1 32 Regu l ator y Action: Section 3 Case No.: 7226

TXR N o.: NA CAS No

. : 99 1 29-21-2 MRIO No.: NA 40 CFR: § 180.458

FROM: Laura No ll e n , Biologist a nd Ri s k Assesso r 

# d

# ~**~** Me h e r et Neg u ss i e, Che mi st

# /'teA~**k~~** Whang Phang

, Senio r**ox co** **lo gist** **/vv~ w~**  Ri sk Assessme n t Branch 3 (RAB3) / H ea l th Effects Di v i sion (7509P)

THROUGH: Ch ri st in e Olinger

, Branch C hi ef 

# .# ,# vj' 

# C"

RAB3 / HED (7509P) 

# {;/° t**~**

TO: Sidney Jackso n , Biologist; Barbara Madden

, Team Leader

, RM # 5 Minor Use and Eme r ge n cy Response Branch Heather Garvie, Lisa Pahel, PM Team #24 Registration Di v i sio n (7505 P )

The Registration Division ( RD ) r equested that t h e Health Effects Di v i s i o n (BE D ) conduct a risk
assessment fo r the act i ve in gred i ent (a i ) clethodim. A s umm ary of the fi ndin gs an d an assessment of human health risks r es ultin g from th e proposed a nd r egistere d uses of clethodim

are p r ov id ed in thi s document. T h e toxicology and ha za rd database review was co ndu c ted by Whang Phang ; the drinking wa t e r assessme n t was co ndu cted by Greg Orrick; the di e t a r y a nd residue c h e mi stry reviev,1s we r e conducted by Mehere t Neguss ie ; a nd the occupat ion al/ r es id e nti a l
exposure assessmen t a nd the aggregate hum a n h ealt h risk assess m e n t we r e conducted by Laura No ll en.

Page 1 of 38CLETHO DI M Human Health Risk Assessment DP No

. 0425763

1.0 Executive Sun1mary

.. . ... .. . . ... . ............................................................................ ...... .. . ........ 4 2.0 HED Recommendation s .

... . ... .. .. .. .. ................ .. .. .. .. .. .. ....... ....................................... . ...... . .. 6 2.1 Data Deficiencie s

.. .. . ... . ....... ................................................ . ....................... .. . .. . .. .. .. ........ 6 2.2 Tolerance Considerations

. ... . .................... .. .. ... ......................... .. ............ ..... . .. . .. . ... . .. . .. . . 7 2

. 2

. 1 E nforcement Ana l y tical Method

... .. .. .. ... . ... .. ....... . ... . .. .. .. ......... . .. .. .. . ...................... . ... 7 2.2.2 Recomm e nded Tolerances

....................... ... . ... .. ... .. . ........................................ ..... ...... 7 2.2.3 Revi s ion s to Petitioned-For Tolerance s

..................................................... .. ............. 8 2.2.4 Int e rnati o nal Harmonization

................................ .. ................................................... 9 2

. 3 Labe l R eco mm e ndation s

............. ........... ........... .............. ............ ............... ............ ...... I 0 2.3. l Recomm e ndation s from Re s idue Revi e w s

........ . ..................................................... I 0 2.3.2 Recommendation s from Occupational A ss es s ment..

............................................. I 0 2

. 3.3 Recommendation s from Residential Asses s ment..

. .. .............................. .. . .. . ..... .. . .. I I 3.0 Introdu ction

.. .. . .. .. .. .. .. .. . ... . ... ................... . ............ .. . .... . ... . ....... . .. .. .. . .. .. . .. ...... ........... .. . .. . .. . . 11 3.1 Chemical Identity

............................................... ... . ... .. . .............................. ... . .. . .. . .. .. . ... 1 2 3.2 Phy s ical /C hemical C haracteristic s

.............. .. .. ... .. .. .................................. .. . .......... ..... 1 2 3.3 Pe s ticide Use Pattern

....................................... ............... ................ .. ..................... ....... 12 3.4 Anticipated Exposure Pathw ays

.......................... ...... .............................................. . .. 13 3.5 Consideration of E nvironmental Ju s ti ce

...................................................... . .. .. ......... 14 4.0 Hazard Characterization and Do se- Re s pon s e Assess ment

........ ..... .................... ......... 14 4.1 Summary of Toxicologica l E ffect s

....................... . ...................................... .. .. . ........... 14 4.2 Safety Factor for Infants and C hildren (FQPA Safety Factor)

.................. .. ..... . .. . .. 1 5 4.2.J Comp l eteness of the Toxicology Databa se

.... . .. ..................... . ................ .. .. .... .. .. . .. . . 1 6 4.2.2 Evidence of Ncurotoxicity

............................................................................. .. . .. . .. .. . 

### 1 6 4.2.3 Evidence of Se n s itivity /S u sce ptibility in the Developing or Young Animal..

...... 1 6 4.2.4

. Residual U ncertainty in the E xpo s ure Databa se

................................................... 16 4.3 Toxici ty E ndpoint a nd Point of Departur e ( POD) Selection s

...................... ..... ....... 16 4.3

. 1 Recomm e ndation for Combin in g Routes of Exposure for Agg re ga t e Ri s k Assess ment

.......................... . .. .. . ... .. .. ......................... . ... .. . ... .. .. ................................................. 

### 1 7 4.3.2 Cancer C l a ss ification and Increa s ed Tumor Incidence Ri s k Assess ment Rec o mmendation

......................................................................................................... . .. . ........ 1 7 5.0 Dietary E xpo s ure and Ri s k Assessment

....... .. ... .............. .. .. .. .. . .. .. .. . ... . .. . ...... . .. . ......... . . ... 1 8 5

. 1 Re s idue s of Co ncern Summary and Rationale

... . ... . ... . ... . .. ............. .. . .. . ......... . .. ......... 18 5.2 Food R.e s idue Profil e

....... .. ............................................................................. . .. .. . .. ...... 19 5.3 Water Re s idue Profile

............... ............... ............................ ............ .................. . ..... .... 20 5

. 4 Dietary Ri s k A ssess m e nt

.. .......... . ........................... . ......................................... ..... ....... 20 5

. 4 .1 De s cription of Re s idu e Dat a Use d in Dietary Assess ment

.................................... 20 5.4 .2 Acute Di e tary Ri s k Assessment

..................... .. . ... .. .. .. .. .............................. . .. .. ......... 21 5.4.3 Chronic Di eta r y Ri s k Assessment

.................................. .......... ..... . ......... . ...... ......... 2 1 5.4.4 Cancer Dietary Risk Assessment

.. ... . ... . ... .. .. ... . ....... . ... . ... . ... . .. ..... .. .. . .. .. . ......... . .. ....... 21 5.4.5 Sun1mary Tab l e

......... ........... .... . .......... ... .. .. ........... .. ..................... ........ .. .. ................. 2 1 6.0 Resid e ntial (Non-Occupationa l ) Exposure/Risk Characterization

............................. 22 6.1 Re s idential Ri s k Es timate s for Use in Aggregate Assessment..

................ ........ . .. . .. .. 22 6.2 Re s idential B ysta nder Po s t- a pplication Inh alation E xpo s ure

..................... . . .. . ... .... 23 6.3 Spray Drift

................... ....... .......................................................................................... 23 7. 0 Aggregate Ex po s ure / Ri s k Characterization

.............. ...... ......................................... . .... 24 7. 1 Acute Agg re ga te Ri s k

................. .. ................................................................................ 24

Page 2 of 38

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 3 of 38 7.2 Short

- Term Aggregate Risk

................................ ................................ ........................ 24 7.3 Intermediate

- Term Aggregate Risk

................................ ................................ ........... 24 7.4 Chronic Aggregate Risk

................................ ................................ .............................. 25 8. 0 Cumulative Exposure/Risk Characterization

................................ ............................... 25 9.0 Occupational Exposure/Risk Characterization

................................ ............................ 25 9.1 Short

- /Intermediate

- Term Handler Risk

................................ ................................ .. 25 9.2 Short

- /Intermediate

- Term Post

- Application Risk

................................ .................... 26 9.2.1 Dermal Post

- application Risk

................................ ................................ .................. 27 9.2.2 Inhalation Post

- application Risk

................................ ................................ ............. 27 10.0 References

................................ ................................ ................................ ......................... 27 Appendix A. Toxicology Profile and Executive Summaries

................................ .................. 29 A.1 Toxicology Data Requirements

................................ ................................ ................... 29 A.2 Toxicity Profiles

................................ ................................ ................................ ............ 30 Appendix B. Summary of Field Trial Data

................................ ................................ ............. 35 Appendix C. International Residue Limits

................................ ................................ .............. 36 Appendix D. Physical/Chemical Properties

................................ ................................ ............. 37 Appendix E. Review of Human Research

................................ ................................ ................. 38

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 4 of 38 1.0 Executive Summary

Clethodim, 2

- [(1 E )

- 1

- [[[(2 E )

- 3

- chloro

- 2

- propenyl]oxy]imino]propyl]

- 5

- [2

- (ethylthio)propyl]

- 3

- hydroxy

- 2

- cyclohexen

- 1

- one , is a systemic and selective postemergence cyclohexanedione herbicide used to control annual and perennial grasses

. T he Interregional Research Project Number 4 (IR

- 4) has submitted pesticide petition (PP#) 4E8334

, requesting the establishment of permanent tolerances for resi dues of clethodim in or on Stevia, Pome fruit group 11

- 10, Stone fruit g roup 12

- 12, Bulb o nion subgroup 3

- 07A, Low growing b erry subgroup 13

- 07G (except cranberry), R apeseed subgroup 20A (except flax), S unflower subgroup 20B, Cotton seed subgroup 20C

, and F ruiting vegetable group 8

- 10. In conjunction with this petition, section 3 registration requests were submitted for two end

- use products (EUPs): Select® 2 EC Herbicide (EPA Reg. No. 59639

- 3), and V

- 10137 1 EC (EPA Reg. No. 59639

- 132). The registrant, Valen t U.S.A. Corporation , owns the EUPs associated with this action. Since the last completed risk
assessment to support the registration review of clethodim , there have been no changes to the hazard characterization or hazard profile (N. Tsaur, DP411899, 01/30/2014). This document assesses the exposures and risks from the proposed tolerances and uses of clethodim

Proposed Use Profile Select ® 2 EC Herbicide and V

- 10137 1 EC are emulsifiable concentrate (EC) E U Ps con taining 26.4% and 12.6% clethodim by weight, respectively, that may be applied by ground, aerial or chemigation (Subgroup 3

- 07A only) equipment

. All proposed representative uses with the highest application rates are associated with Select ® 2 EC Herbicide

, with maximum single application rates that range from 0.13 to 0.25 pounds ai per acre (lb ai/A). The maximum number of applications per season or year are not specified. Both labels specify applicators and other handlers must wear coveralls, chemical

- resi stant gloves, shoes plus socks, and protective eyewear. The specified restricted entry interval (REI) on both labels is 24 hours.

Exposure Profile Exposure to clethodim may occur from dietary (food and drinking water) , residential and occupational expos ure sources. Based on all of the proposed application rates and label information, d ietary exposures are expected for acute and chronic durations ; residential handler and post

- application dermal and inhalation exposures are expected only for short

- term dur ations; and o ccupational handler and post

- application dermal and inhalation exposures are expected for both short

- and intermediate

- term durations.

Toxicity/Hazard The risk assessment for clethodim is based on a well

- characterized and complete toxicology database. Overall, the database shows relatively low toxicity. The liver is the target organ based on repeated dosing by either oral or dermal routes in rats, mice

, and dogs. The observed liver effects are characterized by increased liver weight s, clinical chemistry changes, and centrilobular hepatic hypertrophy. Most of the liver effects that occurred at or below 100 m illigrams/kilogram body weight (m g/kg bw) were considered adaptive effects. Decreased body weight was also a common finding acros s studies and species. In the one

- year dog oral toxicity study, hematological changes such as increased platelet and leukocyte counts were also noted.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 5 of 38 Developmental effects were not present in rabbits, and the toxicity data did not show an increased sus ceptibility in the young; the rat developmental toxicity study showed reduced fetal body weights and an increase in the incidence of delayed ossification of the lower vertebrae at the same dose where maternal toxicity was found. Furthermore, neither repro ductive nor offspring effects were seen in the two

- generation rat reproduction study. Therefore, the data support a reduction of the Food Quality Protection Act (FQPA) safety factor to 1X. Clethodim is not genotoxic and is classified as “not likely to be c arcinogenic to humans” based on results from adequate carcinogenicity studies in rats and mice.

It should be noted that a dermal risk assessment was not conducted for clethodim because no systemic toxicity was seen at the limit dose in the route

- specific dermal study, and no concerns for development or reproductive effects were seen.

Dietary Exposure (Food and Water) and Risk Estimates Unrefined acute and chronic dietary exposure assessments were performed for clethodim using tolerance

- level residues and 100 percent crop treated (PCT). The estimated drinking water concentrations (EDWCs) of 1,430 μ g/L and 1,150 μ g/L were directly incorporated into the acute and chronic dietary assessments, respectively. The results of the acute chronic dietary analyses for food and drinking water are below the HED’s level of concern (LOC) for all population subgroups.

Residential Exposure and Risk Estimates The proposed uses are not expected to result in residential exposure; however, residential handler
exposure scenarios for clethodim were previously re assessed using HED’s 2012 Residential SOPs 1



### . All risk estimates for residential assessments do not exceed HED’s LOC , i.e. a margin of exposure ( MOE ) of 100 ( D412295, Barry O’Keefe , 11/20/2013)

. Residential post

- ap plication exposures were not assessed because no dermal endpoints or points of departure (PODs) were identified for clethodim. The potential for incidental oral exposures to clethodim is expected to be negligible because the extent to which young children utilize these areas or engage in the types of activities associated with these areas (i.e., ornamental landscapes) is low and the potential for exposure via non

- dietary ingestion for young children is unlikely.

Aggregate Exposure Risk Estimates There is p otential for short

- term aggregate exposure to clethodim for adults via the dietary (background e xposure) and residential ( primary exposure ) pathways

. The resulting MOE is 2,200, which does not exceed HED’s LOC, i.e. an MOE of 100. All other aggregate risk estimates are expected to be equivalent to acute and chronic dietary (food and drinking water) risk estimates.

Occupational Handler and Post

- Application Exposures and Risk Estimates Occupational handler and post

- application exposures to clethodim are exp ected for short

- and intermediate

- term durations based on the proposed uses. Although occupational dermal exposure is expected during treatment of agricultural crops, dermal hazard was not identified for clethodim. Therefore, quantitative dermal risk asses sments were not conducted. Because the

1 Available: http://www2.epa.gov/pesticide

- science

- and

- asses sing

- pesticide

- risks/standard

- operating

- procedures

residential

- pesticide

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 6 of 38 short

- and intermediate

- term inhalation PODs are the same, short

- term exposure risk estimates are protective of intermediate

- term exposures and risks. Existing occupational risk assessments are protective of the propo sed uses, with the exception of broadcast applications in orchards/vineyards using groundboom equipment . The results of the occupational handler exposure and risk assessment indicate that short

- /i ntermediate

- term inhalation risks are not of concern at base line mitigation without personal protective equipment (PPE)

. T he 24

- hour REI proposed on both EUPs associated with this action is adequate to protect agricultural workers from post

- application exposures to clethodim.

Environmental Justice Potential areas of environmental justice concerns, 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 Lo w

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

Review of Human Research This risk assessment relies in part on data from studies in which adult huma n subjects were intentionally exposed to a pesticide or other chemical. These data, which include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1) and the Agricultural Handler Exposure Task Force (AHETF), are (1) subject to ethics review pursuan t to 40 CFR 26; (2) have received 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 o n their use, can be found at the Agency website 2



### .

2.0 HED Recommendations

HED has examined the toxicology and residue chemistry databases for clethodim. Pending submission of revised Sections B and F, and analytical reference standards

, there are no issues that would preclude the establishment of the recommended tolerances. Specific tolerance recommendations are discussed in Section 2.2 and label modifications are discussed in Section 2.3.

2.1 Data Deficiencies

There are no data gaps that nee d to be fulfilled for the requested actions. However, an analytical reference standard for clethodim and clethodim S

- methyl sulfoxide must be submitted (e mail communication w ith Teresa Cole, ACB, 03/24/2015) . The registrant is required to submit a reasonab le amount of the analytical reference standard s. The reference standard s should be sent to the Analytical Chemistry Lab, which is located at Fort Meade, Maryland, to the attention of either Theresa Cole or Thuy Nguyen at the following address:

USEPA Nat ional Pesticide Standards Repository/Analytical Chemistry Branch/OPP

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

- exposure

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

- app

- exposure

- data.html

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 7 of 38 701 Mapes Road Fort George G. Meade, MD 20755

- 5350

(Note that the mail will be returned if the extended zip code is not used.)

2.2 Tolerance Considerations

I R

- 4 has submitted PP# 4E8334 in order to propose a tolerance for residues of clethodim in or on Onion, bulb subgroup 3

- 07A at 0.2 parts per million (ppm) ; Vegetable, fruiting group 08

- 10 at 1.0 ppm ; Fruit, pome group 11

- 10 at 0.2 ppm ; Fruit, stone group 12

- 12 at 0.2 ppm ; Berry, low growing, subgroup 13

- 07G, except cranberry at 3.0 ppm ; Rapeseed subgroup 20A, except flax at 0.5 ppm ; Sunflower subgroup 20B at 5.0 ppm ; Cottonseed subgroup 20C at 1.0 ppm ; and Stevia at 12 .0 ppm.

2.2.1 Enforcement Analytical Method

Adequate analytical methods are available for tolerance enforcement purposes for the residues of concern in or on plant and livestock commodities.

Adequate gas chromatography with flame photometric detection (GC/FPD) methods are available for the enforcement of tolerances for clethodim and its regulated metabolites. In conjunction with several petitions, Method RM

- 26B

- 2 has been adequately validated for the analyses of residues of clethodim sulfoxide and its metabolite (5

- OH clethodim sulfone) in/o n crop matrices. Method RM

- 26B

- 2 has undergone a successful validation in EPA Laboratories. Method RM

- 26B

- 3 (a modification of RM

- 26B

- 2) was subsequently submitted and has also been successfully validated in conjunction with several petition reviews. Thes e methods determine total residues of clethodim as two common moieties (clethodim sulfoxide and 5

- OH clethodim sulfone) in crop commodities.

A confirmatory method, RM

- 26D

- 2 is also available. Both methods (RM

- 26B

- 2 and RM

- 26D

- 2) have been forwarded to FD A as enforcement methods for publication in Pesticide Analytical Manual, Volume II ( PAM II )

. Adequate analytical methodology is available to enforce tolerances for clethodim residues of concern in animal commodities. The compound specific method, EPA

- RM

- 2 6D

- 2, is suitable for enforcement of tolerances for total clethodim residues in crops and animal tissues, and it has been forwarded to FDA for publication in the PAM II. The common moiety method, RM

- 26B

- 2, serves as the enforcement method for milk

, as RM

- 2 6D

- 2 is not quantitative for milk.

2.2. 2 Recommended Tolerances

Tolerances for residues of clethodim are established under 40 CFR §180.458 for residues of the herbicide, clethodim, 2

- [(1E)

- 1

- [[[(2E)

- 3

- chloro

- 2

- propenyl]oxy]imino]propyl]

- 5

- [2

- (ethylthio)p ropyl]

- 3

- hydroxy

- 2

- cyclohexen

- 1

- one, including its metabolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulphoxides and sulphones, calculated as the stoichiometric equival ent of

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 8 of 38 clethodim. The currently established tolerance expression for clethodim is adequate, and includes coverage and compliance statements for enforcement purposes. HED recommends that 40 CFR §180.458 be amended by establishing tolerances as listed in Tab le 2.2.2 .1 below

.

Table 2.2.2.1 Tolerance Summary for Clethodim. Commodity Proposed Tolerance (ppm) Recommended/

Harmonized Tolerance (ppm) Comments; Correct

Commodity Definition

Onion, bulb s ubgroup 3

- 07A 0.2 0.5 0 Onion, bulb, subgroup 3

- 07A

. Increased tolerance to harmonize with Codex. Vegetable , fruiting g roup 0 8

- 10 1.0 1.0 Vegetable

, f ruiting, gr oup 8

- 10 Fruit, p ome g roup 1 1

- 10 0.2 0.2 0 Fruit, pome, group 11

- 10
Fruit , stone group 12

- 12 0.2 0.2 0 Fruit, stone, group 12

- 12 Berry, l ow g rowing , s ubgroup 13

- 07G , except cranberry 3.0 3.0

Rapeseed subgroup 20A , except flax 0.5 0.5 0 Rapeseed subgroup 20A

, except flax seed Sunflower subgroup 20B 5.0 5.0 Cottonseed subgroup 20C 1.0 1.0 Cotton seed subgroup 20C
Stevia 12.0 12 Stevia, dried leaves

Table 2.2.2.2 Tolerances Recommended for Revocation for Clethodim Commodity Established

Tolerance (ppm) Recommended

Tolerance (ppm) Comments

Bean, dry, seed 2.5 Revoke Covered by V egetable, legume, group 6, except soybean tolerance at 3.5 ppm
Potato 0.5 Revoke Covered by Vegetable, tuberous and corm, subgroup 1C tolerance at 1.0 ppm Onion, bulb 0.20 Revoke Covered by On ion, bulb, subgroup 3

- 07A at 0.5 0 ppm Vegetable, fruiting group 8 1.0 Revoke Covered by V egetable, fruiting, group 8

- 10

Peach 0.20 Revoke Covered by Fruit, stone, group 12

- 12 Strawberry 3.0 Revoke Covered by Berry, low growing, subgroup 13

- 07G, except cranberry Canola, seed 0.50 Revoke Establish as Rapeseed s ubgroup 20A, except flax seed at 0.50 ppm Mustard, seed 0.50 Sesame, seed 0.35 Safflower, seed 5.0 Revoke Establish as Sunflower s ubgroup 20B at 5.0 ppm Sunflower, seed 5.0 Cotton, undelinted seed 1.0 Revoke Establish as Cottonseed s ubgroup 20C at 1.0 ppm



### 2.2. 3 Revisions to Petitioned

- For Tolerances

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 9 of 38 As summarized below, some of the propose d tolerances are different than those recommended by HED. The registrant should submit a revised Section F in which the proposed tolerances and the correct commodity definitions are the same as those recommended by HED

. For bulb onion, pome fruit, stone fruit, and rapeseed commodities

, the recommended tolerances include an additional significant figure ( e.g ., as 1.0 ppm rather than 1 ppm). This is in order to avoid the situation where rounding of a residue result to the level of precision of the tolerance expression would be considered non

- violative (such as 1.4 ppm being rounded to 1 ppm).

The petitioner had requested to establish a tolerance in or on Onion, bulb subgroup 3

- 07A at 0.2 ppm. However, HED is recommending a tolerance at 0.50 ppm in order to harmonize with established Codex maximum residue limit s (MRL) on onion and garlic . HED is also recommending to update to the correct commodity definition of Onion, bulb, subgroup 3

- 07A.

The petitioner had requested to establish tolerances on V egetable , fruiting group 08

- 10; F ruit

, pome group 11

- 10; Fruit, stone group 12

- 12; and R apes eed subgroup 20A, except flax . The changes were limited to the commodity definitions to reflect the current commodity definition used by the Agency

. Additionally, though IR

- 4 proposed a tolerance on stevia, HED is recommending a tolerance on stevia, dried leaves because the dried commodity represents stevia that will be found in the U.S. trade market.

2.2. 4 International Harmonization

There are Canadian and Codex MRLs for residues of clethodim and its metabolites for some of the proposed crops

.

There are Codex MRLs established on onion

, bulb and garlic (0.5 ppm), tomato (1 ppm),
rape seed (0.5 ppm), sunflowe r seed (0.5 ppm), and cotton seed (0.5 ppm).

The U

. S

. tolerance for R apeseed subgroup 20A (0.50 ppm) and Onion, bulb, subgroup 3

- 07A (0.50 ppm) are harmonized with the Codex rapeseed (0.5 ppm) and bulb onion and garlic (0.5 ppm) MRL s, respectively

.

The U.S. and Cod ex MRLs are not harmonized for S unflower subgroup 20B or C ottonseed subgroup 20C which were established by Codex in or on sunflower seed (0.5 ppm) and cotton seed (0.5 ppm), respectively. The U

. S . tolerance on S unflower subgroup 20B (5.0 ppm) and Cotton seed subgroup 20C (1.0 ppm) could not be harmonized with the Codex sunflower seed and cotton seed MRL s at 0.5 ppm, since the MRL values are lower than the recommended US tolerances. The se U.S. tolerances cannot be harmonized because following the approved label directions could result in residues above the recommended tolerances.

The U

. S

. tolerance on Crop subgroup 3

- 07A (0. 5 0 ppm) cannot be harmonized with the Canadian MRL established on onions (0.2 ppm) , as the U.S. is establishing the Subgrou p 3

- 07A tolerance to harmonize with Codex at a higher tolerance level.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 10 of 38 The value for the U

. S

. tolerance on V egetable , fruiting, group 8

- 10 (1 ppm) is h armonized with the Codex tomato (1 ppm) MRL. However, the Codex MRL was established on tomato only and d oes not include the other representative commodities of Crop g roup 8

- 10.

The U

. S

. tolerance on R apeseed subgroup 20A (0.50 ppm) could not be harmonized with the Canadian MRLs on rapeseed (0.0 5 ppm) or mustard seed (0.4 ppm)

, since the Canadian MRLs

are established on individual crops. In addition, the C anadian MRL value is lower for r apeseed (representative commodity).

The U

. S

. tolerance on S unflower subgroup 20B (5.0 ppm) could not be harmonized with the Canadian crop subgroup MRL

, since the MRL value is lower (0.2 ppm) tha n the recommended U.S. tolerance.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

Overall the directions for use for EPA Reg. No. 59639

- 132 and 59639

- 3 differ from the corresponding propose d use pattern of Section B of the petition in the list of crops, application rate and/or PHI. The petitioner must submit revised labels or Section Bs to match the proposed use patterns.

The proposed labels for EPA Reg. No. 59639

- 132 and 59639

- 3 must be revised as follows:

 to modify the label and Section B “Berry (low growing) except Cranberry” with “Berry low growing (except Cranberry and Strawberry”);

 to revise the Section B for Low growing berry subgroup 13

- 07G (except cranberry) to match the label directions for use application rate and/or PHI; specify that PHI is different for Strawberry.

 to modify the label and Section B “Rapeseed (except flax) Subg roup 20A” with “Rapeseed Subgroup 20A (except flax seed, mustard seed, and sesame seed”);

 to revise the Section B for Rapeseed Subgroup 20A (except flax) to match the label directions for use application rate and/or PHI; specify that application rate and/ or PHI are different for flax seed, mustard seed, and sesame seed.

 to revise the labels for pome fruits and stone fruits to match the proposed single application rate of the Section B which reflects the submitted field trial data.

The proposed labels for EPA Reg. No. 59639

- 3 must be revised as follows:

 to add the statement (under Restrictions): “Do not plant rotational crops until 30 days after application of Select 2 EC Herbicide unless the crop is listed on Select 2 EC Herbicide label”.

2.3.2 Recommend ations from Occupational Assessment

The use directions for the Select® 2 EC Herbicide label (EPA Reg. No. 59639

- 3) should be revised for the Onion, bulb, subgroup 3

- 07A entry to specify a maximum single application rate of “16 fl oz (0.250 lb ai) per acre per application” rather than “per year”. Further, the proposed

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 11 of 38 labels (i.e., Select® 2 EC Herbicide [EPA Reg. No. 59639

- 3] and V

- 10137 1 EC 59639

- 132 [EPA Reg. No. 59639

- 132]) list the commodities under the use directions for Rapeseed subgroup 20A and Sun flower subgroup 20B. However, separate previously

- registered use directions for mustard seed, sesame and safflower appear on the labels. Therefore, the label entry for Rapeseed subgroup 20A should include the language “except mustard seed and sesame” and t he entry for Sunflower subgroup 20B should include “except safflower” so it is evident that separate use directions appear for those specific subgroup members. For EPA Reg. No. 59639

- 3, the formatting for the entry for the Stone fruit crop group 12

- 12 shou ld be revised to correct the formatting of group member entries; and the entry for strawberry should be removed, as it is a member of Low growing berry subgroup 13

- 07G.

2.3.3 Recommendations f rom Residential Assessment

Some clethodim products are intende d for use by residential applicators in residential areas

, but include requirements for certain clothing and/or personal protective equipment (PPE) to be worn on the product labels. Thus, the standard assumptions for residential/consumer applicator specifi c assessments regarding clothing, such as wearing shorts and a t

- shirt without PPE (i.e., chemical

- resistant gloves or respirators), would represent non

- compliance with currently registered products. If products containing clethodim a re intended to be mark eted toward and applied by consumers/homeowners on residential ornamental plant beds, trees, or gro und covers, HED recommends that label requirements for clothing and/or PPE be reevaluated or separate

consumer

- specific labels removing requirements for spec ific clothing or PPE be dev eloped.

3.0 Introduction

Clethodim is a selective post

- emergence c yclohexanedione herbicide used to control annual and perennial grasses around a wide variety of broad leaf crops. It is rapidly absorbed and readily translocated from treated foliage to t he roots as well as other growing plant parts. In plants, clethodim inhibits acetyl

- C oA carboxylase, which regulates fatty acid metabolism. Clethodim is currently registered for use on a variety of agricultural crops and non

- food uses, including residential landscaped areas

. In conjunction with this petition, section 3 registration requests were proposed for Select® 2 EC Herbicide (EPA Reg. No. 59639

- 3), and V

- 10137 1 EC (EPA Reg. No. 59639

- 132) to add Stevia, Pome fruit group 11

- 10, Stone fruit g roup 12

- 12, Bulb o nion subgroup 3

- 07A, Low growing b erry subgroup 13

- 07G (except cranberry), R apeseed subgroup 20A (except flax seed ), S unflower subgroup 20B, Cotton seed subgroup 20C

, and Fruiting vegetable group 8

- 10. The registr ant, Valent U.S.A. Corporation , owns the EUPs associated with this action.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 12 of 38 3.1 Chemical Identity

Table 3.1

. Test Compound Nomenclature

Chemical Structure

Empirical Formula C 17 H 26 ClNO 3 S

Common Name Clethodim Company experimental name RE45601

IUPAC name ( 5RS )

- 2

- { (E)

- 1

- [( 2 E )

- 3

- chloroallyloxyimino]propyl }

- 5

- [ ( 2 RS )

- 2

- (ethylthio)propyl]

- 3

- hydroxycyclohex

- 2

- en

- 1

- one

CAS Name 2

- [(1 E )

- 1

- [[[(2 E )

- 3

- chloro

- 2

- propenyl] oxy]imino]propyl]

- 5

- [2

- (ethylthio)propyl]

- 3

- hydroxy

- 2

- cyclohexen

- 1

- one CAS Registry Nu mber 99129

- 21

- 2

Chemical Class cyclohexenone Known Impurities of Concern None



### 3.2 Physical/Chemical Characteristics

The physi c ochemical properties of clethodim are summarized in Appendix D . Clethodim has a low vapor pressure (<1x10

- 7 

### mm Hg). Thus, clethodim is unlikely to volatilize significantly. Clethodim has a relatively high octanol/water partition coefficient log (K ow 

### ) of 4.51 (at 20°C) which indicates moderate fat solubility ; however, studies show minimal potential for bioaccumu lation. At 20°C, the Henry’s Law constant was calculated to be <2×10

- 9 

### atm·m 3 

### /mol based on vapor pressure and water solubility. Clethodim is hydrolytically stable under acid and neutral conditions, and has some water solubility.

3.3 Pesticide Us e Pattern

Table 3.3. Su mmary of Directions for Use of Clethodim

.

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No. 59639

- 3 ] 1 Max.

Single Applic. Rate (lb ai/A) Max. No.

Applic.
per Season Max.

Annual Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Bulb onion subgroup 3

- 07A Chemigation via sprinkler irrigation; spot treatment; aerial EC 0.25 NS 2 0.5 45 For repeat applications make on a minimum of a 14 day interval.
Pome fruit group 11

- 10 3

G round (incl. spot treatment) ; aerial EC 0.125 NS 0.5 14 For repeat applications make on a minimum of a 14 day interval.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 13 of 38 Table 3.3. Su mmary of Directions for Use of Clethodim

.

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No. 59639

- 3 ] 1 Max.

Single Applic. Rate (lb ai/A) Max. No.

Applic.
per Season Max.

Annual Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Stone fruit group 12

- 12 3
Ground (incl. spot treatment); aerial EC 0.125 NS 0.5 14 For repeat applications make on a minimum of a 14 day interval. Low growing berry, subgroup 13

- 07G, except cranberry
Ground (incl. spot treatment); aerial EC 0.125 NS 0.5 70 For repeat applications make on a minimum of a 14 day interval. Rapeseed subgroup 20A, except flax seed

Spot treatment; ground; aerial EC 0.094 1 0.094 Not for use in California. Do not apply after crop has begun bolting. Crop injury may occur during the bloom period. Sunflower subgroup 20B
Ground (incl. spot treatment); aerial EC 0.25 NS 0.5 70 For repeat applications make on a minimum of a 14 day interval. Cottonseed subgroup 20C

Ground (incl. spot treatment); aerial EC 0.25 NS 0.5 60 For repeat applications make on a minimum of a 14 day interval. Do n ot graze treated fields or feed treated forage or hay to livestock. Stevia
Ground (incl. spot treatment); aerial EC 0.125 NS 0.5 14 For repeat applications make on a minimum of a 14 day interval. Fruiting vegetable 8

- 10
Ground (incl. spot treatment); aerial EC 0.125 NS 0.5 For repeat applications make on a minimum of a 14 day interval. 1 All repr esentative uses with the highest application rates = EPA Reg. No. 59639

- 3. These uses are also proposed for EPA Reg. No. 59639

- 132 at lower single and maximum application rates. 2 NS = not specified 3 The proposed uses quantitatively assessed in associ ation with this action.



### 3.4 Anticipated Exposure Pathways

RD has requested an assessment of human health risk to support the proposed new uses of clethodim in or on Stevia, Pome fruit group 11

- 10, Stone fruit g roup 12

- 12, Bulb o nion subgroup 3

- 07A, Low growing b erry subgroup 13

- 07G (except cranberry), R apeseed subgroup 20A (except flax), S unflower subgroup 20B, Cotton seed subgroup 20C

, and Fruiting vegetable group 8

- 10. Humans may be exposed to clethodim in food and drinking water, since clethodim may be

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 14 of 38 applied directly to growing crops and application may result in clethodim reaching surface and ground water sources of drinking water. There are existing residential uses of clethodim as well as the potential for exposures following spray drift, so there is the potential for exposure in residential or non

- occupational settings. In an occupational setting, applicators may be exposed while handling clethodim prior to application, as well as during application. There is also potential for post

- application exp osure for workers re

- entering treated sites.

Risk assessments have been previously conducted for clethodim, but no new toxicity data have been received since the previous risk assessment. A detailed description of the toxicity data and metabolism information may be found in the preliminary risk asses sment for registration review of clethodim, dated 0 1/30/2014 (N. Tsaur, D411899). This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of clethodim, but also considers the existing uses as well, particul arly for the dietary and residential exposure
assessments.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, 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.epa.gov/environmental justice/resources/policy/exec_order_12898.pdf ). As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according
t o well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns 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 consumption patterns are compiled by the U .S. Department of Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all regist ered food uses of a pesticide. These data are analyzed and categorized by subg roups based on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when condit ions or circumstances warrant. Whenever appropriate, non

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

- application are evaluated. Spray drift can also potentially result in post

- application exposure and it has been considered during the registration review process for clethodim. Further considerations are also currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to other types of possible bystander exposure s and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

No new toxicity data have been received since the las t risk assessment. This assessment includes summaries of prior assessments (N. Tsaur, DP411899, 01/30/2014)

4.1 Summary of Toxicological Effects

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 15 of 38 In general, the clethodim toxicity database shows relatively low toxicity. With repeated dosing by the oral o r dermal routes, the liver is the target organ of clethodim toxicity. Liver effects (characterized by increased liver weights, clinical chemistry changes, and centrilobular hepatic hypertrophy) were seen in rats, mice, and dogs. Clinical chemistry changes include the following: slight alkaline phosphatase increase and slight elevation of cholesterol values. However, most of the liver effects produced by clethodim at 100 mg/kg/day or below were shown to be adaptive effects. Decreased body weight was also a c ommon findi ng across studies and species. In the one

- year oral toxicity study in dogs, hematological changes (increased platelet and leukocyte counts) and slight elevation of glucose levels (in dogs only) were also

seen.
No developmental effects were pre sent in the rabbits. In the rat developmental toxicity study, reduced fetal body weights and an increase in the incidence of delayed ossification of the lower vertebrae were seen at the dose where maternal toxicity was also found. No reproductive or offspr ing effects were seen in the two

- generation rat reproduction study. Therefore, the toxicity data showed no increased susceptibility in the young. Treatment related increase in tumor incidence was not observed in rat and mouse carcinogenicity studies. Clet hodim is not genotoxic and was classified as “not likely to be carcinogenic to humans.” It is also not immunotoxic.

Oral administration of clethodim to rats resulted in rapid absorption with greater than 89% of the administered dose absorbed. The absorbed clethodim was distributed to blood, kidneys, liver, adrenal, and other tissues with the adrenal glands show ing the highest concentration of clethodim equivalents . There was no difference in the concentration of radiocarbon in the tissues between the repea ted dose group and single dose group. The absorbed clethodim was extensively metabolized by (1) oxidation to clethodim sulfoxide and further to clethodim sulfone, (2) converted to S

- methyl via sulfonium cation intermediate, (3) converted to imine, or (4) h ydroxylated at the 5 position. The predominant metabolite was clethodim sulphoxide (48

- 68%). Elimination was rapid; most of the recovered dose in all treatment groups was eliminated after 48 hours with <1% eliminated as parent clethodim. Clethodim was show n to be eliminated mostly via the urine (87

- 92%), and a relatively minor percentage was eliminated via feces (9.3

- 17%). Excretory metabolites which accounted for more than 5% each of the administered dose were: clethodim sulfoxide (48

- 63%), S

- methyl sulfox ide (6

- 12%), and imine sulfoxide (7

- 10%). There was no gender difference in the rate of elimination, and the urinary metabolite profile was very similar for males and females. Bioaccumulation was not demonstrated. The total dermal absorption for clethodim should be 42.0% of the applied dose with 10 hours of exposure.

Clethodim has low acute toxicity via oral, dermal and inhalation routes of exposure as demonstrated by the toxicity categories (III & IV). Clethodim produces mild ocular irritation (Category I II) and mild skin irritation (Category IV) , but i t is not a dermal sensitizer.

4.2 Safety F actor for Infants and Children (FQPA Safety Factor)

For all asses sment scenarios, the data support the 10X FQPA Safety Factor (SF) be reduced to 1X for the following conclusions: (1) The toxicological database for clethodim is complete; (2) there is no evidence of susceptibility following pre

- or postnatal exposure in the young; (3) there

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 16 of 38 is no evidence of neurotoxicity; and (4) there are no residual uncertainties in the exposure database. Th e details for these determination s are presented in the following sections :

4.2.1 Completeness o f the Toxicology Database

The toxicity database for clethodim is complete and sufficient for selecting toxicity endpoints and PODs for risk assessment. The required subchronic inhalation study was waived by the Hazard and Science Policy Council (HASPOC, TXR 0056491, 2/20/2013). The selected toxicity endpoints and PODs for risk assessment are based on the most sensitive and relevant data.

4.2.2 Evidence of Neurotoxicity

In two acute neurotoxicity studies in rats, clinical signs such as decreased spontaneous activity, ruffled fur, hunched posture, and abnormal gaits were seen at 1000 mg/kg /day duri ng the first three days after dosing. Subsequently, treatment

- related clinical signs were not present, and there

were no histopatholog ical findings in the brain or peripheral nervous system. Furthermore, evidence of neurotoxicity was not found in the subchronic neurotoxicity study in rats. Therefore, the transient clinical signs may indicate general malaise of the treated animals which received a limit dose of clethodim (1000 mg/kg/day), and a developmental neurotoxicity study is not required.

4.2.3 E vidence o f Sensitivity/Su sceptibility in the Developing o r Young Animal

As described in Section 4.1, no developmental effects were seen in rabbits and delayed ossification in rats was observed at the same doses as maternal toxicity. No offspring and
repro ductive effects were found in the 2

- generation reproduction study in rats. Therefore, t here is no evidence of susceptibility following in utero or postnatal exposure in the developmental toxicity studies in rats or rabbits, or in the two

- generation rat rep roduction study conducted for clethodim

.

4.2.4 Residual Uncertainty in the Exposure Datab ase
The exposure databases are complete for the purposes of risk assessment. The acute and chronic dietary food exposure assessments were conservatively based on 100 percent crop treated (P CT ) assumptions and conservative drin king water modeling estimates. There are no residential or homeowner uses that result in exposures to children that would be relevant to the aggregate risk assessment. All of the exposure estimat es are based on conservative assumptions that are not likely to result in underestimated risk.

4.3 Toxicity Endpoint and Point of D eparture (POD) Selections

Since the last published risk assessment for clethodim, there have been no changes to the dose

re sponse assessment. There have also been no changes to the prior recommendations regarding the cancer classification or in combining routes of exposures for clethodim. Please refer to Table 4 .3 for detailed information regarding the toxicity endpoints and the points of departure selections.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 17 of 38 It should be noted that a dermal toxicity endpoint and POD for dermal risk assessment for clethodim were not selected because no systemic toxicity was seen at the limit dose in the route

specific dermal toxicity study, and no concerns for development al or reproductive effects were seen elsewhere in the database.

4.3.1 Recommendation for Combining Routes of Exposure for Aggregate Risk Assessment

No dermal haz ard has been identified for clethodim . O ral and inhalation routes can be combined for short

- term risk assessments, due to the selection of a common toxi cological endpoint of

concern. The short term assessment is protective of intermediate

- term exposures.

4.3.2 Cancer Classification and Increased Tumor Incidence Risk Assessment Recommendation

Increased tumor incidence was not seen in carcinogenicity studies in rats and mice, and clethodim is classified as “Not likely to be Carcinogenic to Humans.” Cancer r isk assessments do not need to be conducted.

Table 4 .3. Summary of Toxicological Doses and Endpoints for Clethodim for Use in Dietary, Non

Occupational, and Occupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/

F QPA Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (All Populations) NOAEL =

100 mg/kg/day UF A = 10X

UF H = 10X FQPA SF= 1X RfD = 1

mg/kg/day

aPAD = 1 mg/kg/day Acute neurotoxicity studies

- rats

LOAEL =1000 mg/kg based on clinical observation from two acute neurotoxicity studies. The clinical observation s included decreased spontaneous activity, ruffled fur, head tilt, and hunched posture

Chronic Dietary (All Populations) NOAEL =

30 mg/kg/day UF A = 10X

UF H = 10X FQPA SF= 1X RfD = 0.3

mg/kg/day

cPAD = 0.3 mg/kg/day Carcinogenicity study

- mice

LOAEL=150 mg/kg/day based on reduced survival; decreased red cell mass; and increased incidences of bile duct hyperplasia, of pigmentation of the liver, and of foci of amphophilic macrophages in the lung.

Incidental Oral Short

Term (1

- 30 days) NOAEL =

75 mg/kg/day UF A = 10X

UF H = 10X FQPA SF=1X LOC for

MOE = 100 90

- day oral toxicity

- dogs

LOAEL = 125 mg/kg/day based on increased absolute and relative liver weights, and histological changes characterized by cytoplasmic vesiculation and vacuolation of the central lobular hepatocytes in both sexes.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 18 of 38 Table 4 .3. Summary of Toxicological Doses and Endpoints for Clethodim for Use in Dietary, Non

Occupational, and Occupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/

F QPA Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Dermal Short

- Term (1 to 30 days) and Intermediate

Term (1

- 6 months) No dermal endpoint was identified . The NOAEL for the 28

- day dermal toxicity study is the

limit dose of 1000 mg/kg/day.

Inhalation Short

- Term (1 to 30 days) and Intermediate

Term (1

- 6 months) NOAEL =

75 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X LOC for

MOE = 100 90

- day oral toxicity

- dogs

LOAEL = 125 mg/kg/day based on increased absolute and relative liver weights, and histological changes characterized by cytoplasmic vesiculation and vacuolation of the central lobular hepatocytes in both sexes. Cancer (oral, dermal, inhalation) Clethodim is classified as "Not Likely" to be carcinogenic based no treatment

- related

increase in tumor incidence in rat and mouse carcinogenicity studies

. P oint 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 (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). 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.



### 5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

The available metabolism studies for clethodim on soybean, cotton, and carrots indicate that the metabolism in these crops are similar. The maj or metabolic pathways for clethodim (C) in tested crops are initial sulfoxidation to clethodim sulfoxide (CSO) followed by further oxidation to clethodim sulfone (CSO 2 

### ). The elimination of the chloroallyloxy side chain yields the imine sulfoxide (ISO) and sulfone (ISO 2 

### ), and the hydroxylation of these compounds forms the 5

- OH sulfoxide (5OH

- SO) and sulfone (5OH

- SO 2 

### ). Clethodim sulfoxide and clethodim sulfone conjugates were also detected as major or minor metabolites, depending on plant species and sub

- frac tions. Also present as a minor metabolite was the aromatic sulfone. A study designed to follow the fate of the chloroallyloxy group showed that the chloroallyloxy moiety which was cleaved from clethodim underwent extensive metabolism, eliminating the chlo rine atom and incorporating the three carbon moieties into natural plant components (with some being evolved

as 14 

### CO 2 

### ).

A confined rotational crop study of [ring

- 4,6

- 14 

### C]

- clethodim

, conducted with carrots, lettuce, and wheat

, was previously reviewed (MRI D 41030211 ; EFGWB Science Chapter for Clethodim , E.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 19 of 38 B. Conerly , 6/26/90). The study indicated that there is no need for rotational crop field trials and a 1

- month plantback interval for rotational crops is adequate. The general restrictions and limitation s on the label should prohibit planting a rotational crop until 30 days after application of Select 2EC Herbicide unless clethodim is registered for use on that crop.

The nature of the residue in ruminants and poultry is adequately understood

. Metabolism studies of [propyl

- 1

- 14 

### C]

- clethodim in a lactating goat and laying hens have been previously reviewed. HED previously concluded that the residues of concern in livestock are clethodim and its metabolites containing the 2

- cyclohexen

- 1

- one moiety.

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Primary Crop clethodim and its metabolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulfoxides and sulfones, expressed as clethodim clethodim and its metabolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulfoxides and sulfones, expressed as clethodim
Rotational Crop Not applicable Not applicable

Livestock Ruminant clethodim and its metabolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulfoxides and sulfones, expressed as clethodim clethodim and its metabolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethy lthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulfoxides and sulfones, expressed as clethodim Poultry

Drinking Water clethodim and its degradates containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties (including their sulfoxides and sulfones) Not applicable



### 5.2 Food Residue Profile

A dequate residue data are available to support the proposed tolerances for the herbi cide clethodim in/on stevia, pome fruits, stone fruits, and the crop group expansions. For pome fruits and stone fruits the residues of clethodim and metabolites

, determined as the sum of dimethyl esters of clethodim sulfoxide ( DME ) and 5

- hydroxy clethodim sulfone ( DME

- OH)

, we re below the LOQ ( <0.183 ppm) in/on all samples. Residue decline was not investigated.

Adequate processing studies were conducted on apple and plum. Residues of clethodim did not concentrate in apple and plums.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 20 of 38 Adequate storage stability data are available to support the intervals of frozen storage of all raw agricultural and processed commodities from the proposed uses. No corrections for degradation during storage are needed.

The only livestock feedstuff associated with the new uses is apple wet pomace . The current established livestock tolerances are adequate to cover expected residues.

A detailed summary table of the crop field trials may be found in Appendix B.

5.3 Water Residue Profile

The Environmental Fate and Effects Division (EFED) provided the estimated drinking water concentrations (EDWCs) used in the acute and chronic dietary risk assessments (G. Orrick, D 425767

, 3/31/3015 ; G. Orrick, D412704, 6/24/13 )

. EDWCs were incorporated directly into the DEEM

- FCID dietary assessment in the food categories “water, direct, all sources” and “w ater, indirect, all sources.”

B ased on the proposed application rates and the environmental fate properties of clethodim, surface and ground water contamination may occur from clethodim as well as its str ucturally similar degradates. Thus, the assessments were based on the total toxic residues (TTR) rather than parent only. The risk of water contamination is primarily associated with the structurally similar degradates rather than parent clethodim based on greater persistence and mobility of these degradates.

The EDWCs of the previous drinking water assessment were relied upon for this assessment G. Orrick, D412704, 6/24/13

. The maximum screening

- level acute and chronic EDWCs (1,430 and 1,150 μg/L, respect ively) used in the dietary assessment are based on the maximum use pattern for clethodim, which includes non

- cropped areas, fallow ground, alfalfa, and a maximum annual application rate of 4.5 lb ai/A. The EDWCs were estimated with Pesticide Root Zone Mode l for Ground Water (PRZM

- GW) to occur in an area of Wisconsin that is vulnerable to ground water contamination.

Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations for Clethodim.

Source (Tier: Model) Use Site (Max. Annual App. Rate) Acute EDWC (μg/L) Chronic

EDWC (μg/L) Surface water (Tier I: FIRST) Non

- cropped (4.5 lbs a.i./A) 330 137 Ground water (Tier I: PRZM

- GW) Non

- cropped (4.5 lbs a.i./A) 1,430 1,150 Ground water (Tier I: SCI

- GROW) Non

- cropped (4.5 lbs a.i./A) ≤27



### 5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

HED conducted a n unrefined chronic dietary (food and drinking water) risk assessment for clethodim using exposure and risk estimates obtained from the Dietary Exposu re Evaluation Model using the Food Commodi ty Intake Database (DEEM

- FCID; v ersion 3.16). The model uses food consumption data from the Department of Agriculture’s (USDA’s) 2003

- 2008

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 21 of 38 National Health and Nutrition Examination Survey, What We Eat in America ( NHANES/WWEIA) database

. The assessment incorporated tolerance

- level residues and 100 PCT for all established and proposed commodities. The assessment also utilized default processing factors from the DEEM

- FCID v ersion 7.81 except f or tolerances that were

e stablished for processed commodities, or where processing studies indicated that concentration did not occur upon processing . EDWCs were incorporated directly into the dietary assessment from ground water estimates obtained using the PRZM

- GW model.

5.4.2 Acute Dietary Risk Assessment

The results of the acute dietary analysis for food and drinking water are below the Agency’s LOC for the general U.S population and all population subgroups. The dietary (food and drinking water) exposure is estimated at 10 % of the acute Population Adjusted Dose ( a PAD) for the general U.S. population and 29 % of the a PAD for all infants (<1 year old), the population subgroup with the highest estimated chronic dietary exposure to clethodim

. The results of the
acute dietary exposure analyses are reported in Table 5 .4.5

.

5.4.3 Chronic Dietary Risk Assessment

The results of the chronic dietary analysis for food and drinking water are below the Agency’s LOC for the general U.S population and all population subgroups. The dietary (food and drinking water) exposure is estimated at 12 % of the chronic Population Adjusted Dose (cPAD) for the general U.S. population and 30 % of the cPAD for all infants (<1 year old), the population subgroup with the highest estimated chronic dietary exposure to clethodim

. The results of the chronic dietary exposure analyses are reported in Table 5 .4. 5

.

5.4.4 Cancer Dietary Risk Assessment

Increased tumor incidence was not seen in carcinogenicity studies in rats and mice, a nd clethodim is classified as “n ot likely to be carcinogenic to humans;” therefore, cancer risk was not assessed

5.4. 5 Summary Table

T able 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Clethodim.

Population Subgroup Acute Dietary Chronic Dietary Dietary (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.102035 10 0.037592 12

All Infants (< 1 year old) 0.286813 29 0.090304 30

Children 1

- 2 years old 0.177502 18 0.074277 25

Children 3

- 5 years old 0.157066 16 0.061470 20

Children 6

- 12 years old 0.105444 10 0.040639 14

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 22 of 38 T able 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Clethodim.

Population Subgroup Acute Dietary Chronic Dietary Dietary (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

Youth 13

- 19 years old 0.080662 8.1 0.028696 9.6

Adults 20

- 49 years old 0.094225 9.4 0.034796 12

Adults 50

- 99 years old 0.084808 8.5 0.034303 11

Females 13

- 49 years old 0.094612 9.5 0.034543 12



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no proposed residential uses associated with this action; however, there are existing residential uses of clethodim that were previously reassessed to reflect up dates to HED’s 2012 Residential SOPs 3 

### along with policy changes for body weight assumptions (B. O’Keefe, D412295, 11/20/2013). That assessment included short

- term residential handler inhalation exposure assessment for the EUP

, EPA Reg. No. 59639

- 175

, that was conducted to represent the “worst case” high

- end exposure

. A quantitative resident ial post

- application dermal risk
assessment was not conducted because a dermal hazard was not identified. Based upon the residential uses, non

- dietary incidental oral ingestion exposure was not expected and was not assessed. Since the registered product s are intended for use in landscaped areas, orname ntal plant beds, and in and around trees and mulched areas , the potential for exposure via non

- dietary ingestion for young children is unlikely. The extent to which young children engage in the types of activities associated with these areas (i.e., ornamen tal landscapes) or utilize these areas for prolonged periods of play is low.

In accordance with 40 CFR §158, Guideline 875.2100

- Turf Transferable Residues (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. There are no residential turf uses; therefore a TTR study is not required in order to esti mate residential post

- application exposure to turf. Additionally, Guideline 875.2100

- Dislodgeable Foliar Residue (DFR) data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable garde ns, pick your own farms, retail tree farms) uses that could result in post

- application exposure to foliage. Since clethodim does not result in adverse systemic toxicity via the dermal route of exposure, HED does not need a DFR study at this time

.

6. 1 Res idential Risk Estimates for Use in Aggregate Assessment

Table 6.1 reflects the residential risk estimates that are recommended for use in the aggregate assessment for clethodim.

3 Available: http://www.e pa.gov/pesticides/science/residential

- exposure

- sop.html

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 23 of 38  The recommended residential exposure for use in the adult aggregate assessm ent reflects short

- term inhalation exposure from applications in and around ornamental plant beds, trees, and ground covers via backpack sprayer.

 There is no recommended residential risk estimates for children for use in the aggregate assessment, because r esidential risk estimates are expected to be negligible to children.

Table 6.1. Recommendations for the Residential Exposures for the Clethodim Aggregate Assessment.

Lifestage (Scenario) Inhalation Dose (mg/kg/day) 1 MOE 2

Residential Handler

Adult (Backpack Sprayer) 0.00001186 6,300,000
1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. 2 Inhalation MOE = POD ÷ Inhalation Dose (mg/kg/day).



### 6.2 Residential Bystander Post

- application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The A gency sought expert advice and input on issues related to volatilization of pesticides from its Fe deral Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://ww w.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2009

- 0687

- 0037 ). The A gency 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 did not perform a quantitative post

- application inhalation exposure assessment primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( <1x10

- 7 

### mm Hg ), and the low registered use rate s (0.0455 to 0.25 lb ai/A /application). A quantitative spray drift analysis also indicated no risks of concern following spray drift of clethodi m for currently registered agricultural uses.

6.3 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., groundboom) employed for clethodim

. The potential for spray drift was quantitatively evaluated for clethodim during the Registration Review process , utilizing the Standard Operating Procedures For Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift, in order to consider all uses concurrently (D412295, B

. O’Keefe, 11/20/2013). Spray drift risk estim ates from lawn deposition adjacent to agricultural applications of clethodim following groundboom or aerial equipment applications were assessed. As no dermal toxicity endpoint or POD has been identified for clethodim

, only incidental oral risk estimates w ere assessed. The highest exposure resulted from drift following clethodim

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 24 of 38 applications using aerial or groundboom equipment for children 1 to <2 years old. The hand

- to

mouth MOEs modeled at the edge of the field ranged from 53,000 and 110,000 for aerial a nd groundboom scenarios, respectively (LOC = 100) . Therefore, residues of clethodim from spray drift are not of concern to HED.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking wat er, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantit ative estimates of hazard (e.g. a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

7.1 Acute Aggregate Risk

Acute exposure is not expe cted for the residential exp osure pathway. Therefore, the acute aggregate risk would be equivalent to the acute dietary exposure estimate s . Refer to Section 5.4. 2

. for a detailed discussion of the acute dietary assessment.

7.2 Short

- Term Aggregate Risk

There is potential short

- term e xposure to clethodim via the dietary (which is considered background exposure) and residential (which is considered primary exposure) pathways. For adults, the oral and inhalation routes of exposure should be aggregated since the endpoints of

concern are c ommon. The recommended residential exposure for use in the adult aggregate assessment reflects inhalation exposure from applications in and around ornamental plant beds, trees, and ground covers via backpack sprayer. The short

- term aggregate risk estimate (dietary and residential) is not of concern (as presented in Table 7.2)

. The MOE is 2,200, which does not exceed HED’s LOC, i.e. an MOE of 100.

Table 7.2. Short

- Term T erm Aggregate Risk Calculations

Population Short

- or Intermediate

- Term Scenario

NOAEL mg/kg/day LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food and Water Exposure mg/kg/day Residential

Exposure mg/kg/day 3 Total

Exposure mg/kg/day 4 Aggregate

MOE (food, water, and residential) 5

Adults 6 75 100 0.75 0.034796 0.00001186 0.03480786 2,200

1 LOC = 100, 10X UF A , 10X UF H , FQPA SF = 1X.
2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC
3 Residential Exposure = Inhalation Exposure , as noted in Table 6 .1.
4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)
5 Aggregate MOE = [NOAEL/ (Avg Food & Water Exposure + Residential Exposure)]

6 Adults = Adults 20

- 49, the population with the greatest dietary exposure.



### 7.3 Intermediate

- Term Aggregate Risk

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 25 of 38 Intermediate

- term exposure is not expected for the residential exposure pathway. Therefore, the intermediate

- term aggregate risk would be equivalent to the chronic dietary exposure estimate. Refer to Section 5.4.3. for the chronic dietary (food and drinki ng water) exposure assessment.

7.4 Chronic Aggregate Risk

There are no chronic residential exposure scenarios; therefore, the chronic aggregate risk would be equivalent to the chronic dietary exposure estimate. Refer to Section 5.4.3 for the chronic die tary (food and drinking water) exposure assessment.

8.0 Cumulative Exposure/Risk Characterization

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 mecha nism of toxicity finding as to clethodim and any other substances and clethodim 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 clethodim has a common mechan ism 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://www.epa.gov/pesticides /cumulative/

.

9.0 Occupational Exposure/Risk Characterization

This document presents an assessment of the proposed uses of clethodim in or on Stevia, Pome fruit group 11

- 10, Stone fruit g roup 12

- 12, Bulb o nion subgroup 3

- 07A, Low growing b erry subgroup 13

- 07G (except cranberry), R apeseed subgroup 20A (except flax seed ), S unflower subgroup 20B, Cotton seed subgroup 20C

, and Fruiting vegetable group 8

- 10. S hort

- and intermediate

- term occupational exposures to clethodim are expected, b ased on the application rates and label information. Chronic exposure is not expected for the proposed use patterns.

9.1 Short

- /Intermediate

- Term Handler Risk

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially b e used, occupational handler dermal and inhalation exposures are expected from the proposed uses. The occupational exposure assessment for clethodim , associated with registration review ( D412295, Barry O’Keefe, 11/20/2013)

, quantified occupational handler exposure and risk estimates that represent all proposed uses and the risk estimates were not of

concern

. The previous assessment is protective of the proposed uses of clethodim except that groundboom broadcast a pplic ation scenarios for orchards/vineyards w ere not previously assessed . Therefore, this document addresses the occupational handler and post

- application exposure and risk s resulting from broadcast applications of clethodim using groundboom equipment in orchard s or vineyard s only

. T he only quantitat ive exposure/risk assessment scenarios that were assessed for occupational handlers are as follows:

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 26 of 38 1) Mixing/loading liquids for groundboom application 2) Applying sprays via groundboom equipment

The clethodim EUPs direct mixers, loaders, applicators and other handlers to wear long

- sleeved shirt s and long pants, chemical

- resistant gloves such as barrie r laminate or viton ≥ 14 mils, shoes plus socks, and protective eyewear.

The results of the occupational handler ex posure and risk assessment resulting from the proposed use of clethodim are presented in Table 9. 1 and indicate that short

- term inhalation risk estimates do not exceed HED’s LOC (i.e. an MOE < 100 for sho rt

- term exposures) at baseline (i.e., no respirator) . The inhalation MOEs were 3,500,000 and 5,400,000; and therefore are not of concern. Because the short

- and intermediate

- term inhalation PODs are the same, short

- term exposure risk estimates are protective of intermediate

- term exposures.

Table 9.1. Occ upational Handler Non

- Cancer Exposure and Risk Estimates for Clethodim.

Exposure Scenario Crop or Target 2 Level of Concern Inhalation

Unit Exposure (μg/lb ai) 3 Maximum

Application Rate 5 (lb ai/A) Area Treated

or Amount Handled Daily (A) 6 Inhalation

Level of PPE 4 Dose (mg/kg/day) 7 MOE 8

Mixer/Loader
Groundboom Broadcast (EC 1 ) Orchard/vineyard 100 0.219 0.125 4 0 0.0000138 5,400,000 Baseline

Applicator
Groundboom Broadcast (Spray) Orchard/vineyard 100 0.34 0.125 4 0 0.0000213 3,500,000 Baseline

1 EC = emulsifiable concentrate 2 Orchard/vineyard = Pome fruit group 11

- 10 and Stone fruit group 12

- 12 3 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2015); 4 Level of mitigation: Baseline Level of mitigation (single layer clothing, no gloves or respirator)

. 5 Based on proposed label ( EPA Reg. No. 59639

- 3 ). 6 Exposure Scien ce Advisory Council Policy #9.1. 7 Inhalation Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate ( 0.125 lb ai/acre) × Area Treated or Amount Handled Daily ( 40 A) ÷ BW ( 80 kg). 8 Inhalation MOE = POD ( 75 mg/kg/day) ÷ Dose (mg/kg/day).



### 9.2 Short

- /Intermediate

- Term Post

- Application Risk

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 refe rred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as sco uting 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 pes ticide application, and the chem ical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 27 of 38 9.2.1 Dermal Post

- application Risk

Based on the proposed use directions , dermal exposures are expected for workers conducting post

- application act ivities on agricultural crops. However, no dermal toxicity endpoints or PODs

were selected for risk assessment. Therefore, a quantitative dermal post

- appl ication exposure assessment was not performed for clethodim.

Guideline 875.2100

- DFR; Guideline 875.2100

- TTR Since clethodim does not result in adverse systemic toxicity via the dermal route of exposure, HED has determined that DFR and TTR data are no t needed at this time

. Restricted Entry Interval The REI specified on the proposed EUPs is based on th e acute toxicity of clethodim. Clethodim is classified as Toxicity Category IV via the dermal route , Toxicity Category III for eye irritation potential and Toxicity Category IV for skin irritation potential. It is not a skin sensitizer. Under 40 CFR § 156.208 (c) (2) (iii), active ingredients classified as Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12

- hour REI under the 156 subpart K Worker Protection Statement s in order to protect agricultural workers from post

- application exposures to clethodim . Therefore, the 24

- hour REI proposed on both EUPs associated with this action is adequate to protect agricultural workers from post

- application exposures to clethodim.

9.2.2 Inhalation Post

- application Risk

T here are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. T hese potential sources include volatilization of pesticides and resuspension of dusts and/or partic ulates that contain pesticides. Th e A gency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, F ungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.regulations.gov/#! documentDetail;D=EPA

- HQ

- OPP

- 2009

- 0687

- 0037 ). The A gency 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 for clethodim, b ased on the Agency's current practices, a quantitative post

- application inhalation exposure assessm ent was not performed, primari ly because of the low acute inhalation toxicity (Toxicity Category IV), lo w vapor pressure ( <1x10

- 7 

### mm Hg )

, and the low use rate (0. 1 25 lb ai/A).

10.0 References

V . Chen, 07/12/2013

, DP411835, TXR0056668, “ Clethodim : Immunotoxicity Data Review .”

B. O’Keefe, 11/20/2013, DP412295, “ Clethodim. Occupational and Residential Exposure Assessment for Registration Review.” N. Tsaur, 01/30/2014, DP411899, “ Clethodim

. Preliminary Risk Assessment for Registration Review.”

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 28 of 38 L. Nollen, 12/17/2015, DP 425763 , “ Clethodim

. Occupational and Residential Exposure Assessment for Proposed Uses on Stevia , Pome Fruit Group 11

- 10, Stone Fruit Group 12

- 12, Bulb O nion Subgroup 3

- 07A, Low Growing B erry Subgroup 13

- 07G, (except Cranberry); R apeseed Subgroup 20A (except Flax) , S unflower Subgroup 20B, Cotton seed Subgroup 20C

, and Fruiting Vegetable Group 8

- 10 .”

M. Negussie, 01/12/2016, DP4 31225 , Clethodim: Tolerance Petition for New Uses on Stevia; Pome Fruit Crop Group 11

- 10; Stone Fruit Crop Group 12

- 12; and Crop Group/Subgr oup Expansions for Onion, Bulb Subgroup 3

- 07A; Fruiting Vegetables Group 8

- 10; Low growing Subgroup 13

- 07G, except cranberry; Rapeseed Subgroup 20A, except Flax Seed; and Cotton seed Subgroup 20C. Summary of Analytical Chemistry and Residue Data

M. Negu ssie, 01/19/2016, DP431223, Clethodim: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for New Uses on Stevia; Pome Fruit Crop Group 11

- 10; Stone Fruit Crop Group 12

- 12; and Crop Group/Subgroup Expansions for Oni on, Bulb Subgroup 3

- 07A; Fruiting Vegetables Crop Group 8

- 10; Low growing Subgroup 13

- 07G, except cranberry; Rapeseed Subgroup 20A, except Flax Seed; Sunflower Subgroup 20B ; and Cottonseed Subgroup 20C.

G. Orrick, 03/31/2015, D425767, “ Clethodim : Drinking Water Exposure Assessment for Proposed New Uses and Crop Group Conversions regarding Stevia, Pome Fruit Group 11

- 10, Stone Fruit Group 12

- 12, Bulb Onion Subgroup 3

- 07A, Low

- growing Berry Subgroup 13

- 07G, Rapeseed Subgroup 20A, Sunflower Subgroup 20B, Cott on Seed Subgroup 20C, and Fruiting Vegetable Group 8

- 10.”

G. Orrick, 06/24/2013, DP412704, “ Clethodim: Drinking Water Exposure Assessment for Registration Review.”

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 29 of 38 A ppendix A . Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements The requirements (40 CFR 158.340) for food uses for the technical, clethodim, are in Table A.1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1. Toxicology Data Requirements for Technical Cleth odim

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 CR (no) CR (yes) yes yes yes

no waived b
870.3700a Developmental Toxicity (rodent)

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

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

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

yes yes 870.4100b Chronic Toxicity (nonrodent)

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

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

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

yes
yes 870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

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

— Structural Chromosomal Aberrations

... 870.5395 Mutagenicity

— Other Genotoxic Effects

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

yes 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 No -

- yes yes

- 870.7485 General Metabolism

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

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

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

no
yes yes

yes
yes

a CR = conditionally required. b HASPOC; 2/20/2013; TXR 0056491

.

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 30 of 38 A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile of Clethodim

Guideline No. Study Type MRID (Date) Results Toxicity Category

870.1100 Acute oral [rat] 40974507 (1986) LD 50 =

males 1.63 g/kg f emales 1.36 g/kg III

870.1200 Acute dermal [rabbit] 40974510 (1986) LD 50 > 5.0 g/kg IV

870.1300 Acute inhalation [rat] 40974512 (1986) LC 50 > 3.9 mg/L IV

870.2400 Acute eye irritation [rabbit] 40974514 (1986) mild ocular

irritation III

870.2500 Acute dermal irritation [rabbit] 40974516 (1986) moderate dermal

irritation III

870.2600 Skin sensitization [ g uinea pig] 40974518 (1986) n ot a dermal

sensitizer N/A

Table A.2.2. Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results
Subchronic Toxicity Studies Note: The NOAEL and LOAEL of some subchronic studies were originally established based on the increased liver weights; those NOAEL and LOAEL were re

- evaluated and raised in accordance to the current policy in evaluating the live r effects

870.3100 5

- Week oral toxicity

(rat) 41030110 (1986)

Acceptable/Nonguideline 0, 5, 200, 1000, 4000, 8000 ppm equivalent to 0, 0.256, 12.5, 65.6, 261, 515 mg/kg/day in males and 0, 0.288, 13.9, 70.6, 291, 554 mg/kg/day in females NOAEL = 65.6/ 70.6 mg/kg/day (M/F) LOAEL = 261/291 mg/kg/day ( M/F) based on hematologic effects, , reduced body weights, and decreased food intake.

870.3100 4

- Week oral toxicity

(mouse) 41030103 (1986)

Acceptable/Non

- guideline 0, 100, 250, 625, 1500, 4000 ppm Calculated by standard conversion factor (1 ppm = 0.15 mg/kg/day): 0, 15, 37.5, 93.8, 225.0, 600.0 mg/kg/day NOAEL = 600 mg/kg/day (H ighest dose tested, H DT)

870.3100 90

- Day oral toxicity

(rat) with 6 week
recovery groups 41030107 (1986)

Acce ptable/Guideline 0, 50, 500, 2500, 5000
ppm 0, 2.3/2.8, 25/30, 134/159, 279/341 mg/kg/day (M/F) NOAEL = 134/159 mg/kg/day (M/F) LOAEL = 279/341 mg/kg/day (M/F) based on decreased body weights

, decreased food consumption, and hematological effects (decreases in hematocrit and hemoglobin).

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 31 of 38 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results

870.3150 90

- Day oral toxicity

(dog) 41030106 (1987)

Acceptable/guideline 0, 1, 25, 75, 125 mg/kg/day NOAEL = 75 mg/kg/day LOAEL = 125 mg/kg/day based on increased absolute liver weights with histological correlat es of cytoplasmic vesiculation and vacuolation of the central lobular hepatocytes in male and female dogs and increases in ALP and cholesterol

.

870.3200 21/28

- Day dermal

toxicity (rat) 41030109 (1987)

Acceptable/non

- guideline 0, 10, 100, 1000 mg/kg/day No adverse systemic toxicity was found; NOAEL = 1000 mg/kg/day (HDT; limit dose) S kin irritation was seen in all treatment groups.

870.3200 21/28

- Day dermal

toxicity (rat) EC formulation (26.3% ai ) 41030201 (1987)

Acceptable/Guideline 0, 10 , 50, 100/200 mg/kg/day (high dose reduced to 100 after 4 applications due to severe irritation) Systemic NOAEL = 200 mg/kg/day [HDT].

D ermal irritation was seen in all treatment
groups.

870.3465 90

- Day inhalation

study Subchronic inhalation toxicity study waived (HASPOC; 2/20/2013;

TXR 0056491) Deve l opmental and Reproductive Toxicity Studies

870.3700a Prenatal

developmental in (rat) 41030114 (1986) pilot

41030116 (1987) Acceptable/Guideline 0, 10, 100, 350, 700 mg/kg/day Maternal NOAEL = 100 mg/kg/day Maternal LOAEL = 350 mg/kg/day based on reduced body weight gains clinical signs of toxicity ( dose

- related increased in the incidence of excessive salivation and lacrimation, red nasal discharge, and an o genital st aining ).

Developmental NOAEL = 100 mg/kg/day Developmental LOAEL= 350 mg/kg/day based on reduced fetal body weights and delayed ossification of the lower vertebrae.

870.3700b Prenatal

developmental in (rabbit) 41030113 (1986) pilot

41030115 (1987) Acce ptable/Guideline 0, 25, 100, 300 mg/kg/day Maternal NOAEL = 100 mg/kg/day Maternal LOAEL = 300 mg/kg/day based on clinical signs of toxicity (incre ased incidence of dried feces), and reduced food consumption.

Developmental NOAEL > 300 mg/kg/day (HDT)

870.3800 Reproduction and

fertility effects (rat) 41030119 (1986) pilot

41030120 (1987) Acceptable/Guideline 0, 5, 20, 500, 2500 ppm 0, 0

- 1/0

- 1, 1

- 2/1

- 3, 28

- 60/36

- 61, 141

- 295/180

- 282 mg/kg/day (M/F) Parental NOAEL = 51 mg/kg/day. Parental LOAEL = 263 mg/kg/day based on reduced body weight, particularly in males, and reduced food consumption during both generations.

Reproductive: NOAEL = 263 mg/kg/day (HDT)

### CLETHODIM Human Health Risk Assessment DP No. D425763

Page 32 of 38 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results
Offspring NOAEL = 263 mg/kg/day. (HDT) Chronic Toxicity S tudies

870.4100b Chronic toxicity

(dog) 41030111 (1988)

Acceptable/Guideline 0, 1, 75, 300 mg/kg/day in capsules NOAEL = 75 mg/kg/day (M/F) LOAEL = 300 mg/kg/day (M/F) based on increases in platelet count, leukocytes, and ALT & ALP activities; decreases in glucose, in RBC, I

- IGB, and HCT levels.

870.4200 Carcinogenicity

(mouse) 78 weeks 41030112 (1988)

Acceptable/Guideline 0, 20, 200, 1000, 2000/3000 ppm (high dose received 2000 ppm for first 15 weeks then increased to 3000 ppm) Calculated by standard conversion factor (1 ppm = 0.15 mg/kg/day): 0, 3, 30, 150, 450 mg/kg/day NOAEL = 30 mg/kg/day LOAEL = 150 mg/kg/day based on treatment

related effects on survival, decreased red cell mass ( decreased erythrocyte counts, hemoglobin, and hematocrit values) , increased liver weight s, and increased foci of amphophilic alveolar macrophages in the lung

, bile duct hyperplasia, and increased pigmentation in the liver.

No evidence of carcinogenicity.

870.4300 Combined Chronic

Toxicity/ Carcinogenicity (rat) 41030121 (1988)

Acceptable/Guideline 0, 5, 20, 500, 2500 ppm (M: 0, 0.15, 0.57, 16, and 86 mg/kg/day; F: 0, 0.2, 0.72, 21, and 113 mg/kg/day). NOAEL = 21 mg/kg/day LOAEL = 113 mg/kg/day based on significant decreases in mean body weights in females

No evidence of carcinogenicity.

Genotoxicity B attery

870.5100 Gene Mutation 41030122 (1986) Acceptable up to 10,000 μg/plate Negative. There was no evidence of induced mutant colonies over background in strains TA98, TA100, TA1535 and TA1537 with and without S9 activation.

870.5100 Gene Mutation 41030123 (1986) Acceptable up to 10,000 μg/plate Negative. There was no evidence of treatment

related induced mutant colonies over background in strains TA98, TA100, TA1535, TA1537, or WP2 with or without S9 activation.

870.5375 CHO Assay 41030128 (1986) Acceptable 1.0 and 1.2 μl/ml Positive. There was evidence of a dose

- related increase in structural chromosomal aberrations over background in the absence of metabolic activation at concentrations near the li mits of solubility and cytotoxicity.

870.5375 CHO Assay 41030129 (1986) Acceptable up to levels of insolubility 0.3 and 1.0 μl/ml Negative. There was no evidence of a dose

related increase in structural chromosomal aberrations over background in the presence or absence of metabolic activation at any concentration tested up to the limit of solubility.

870.5395 Micronucleus Assay

(rat) 41030125 (1987)

Acceptable up toxic dose 1,500 mg/kg/day (gavage) Negati ve. There is no evidence that c lethodim induced chromosomal aberrations in bone marrow cells of rats over background levels.

870.5550 Unscheduled DNA 41030124 (1986) Negative. There was no evidence that

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Page 33 of 38 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results
Synthesis (mouse) Acceptable

up to lethal level 5,000 mg/kg/day unscheduled DNA synthesis, as determined by radioactive tracer procedures [nuclear silver grain counts] was induced. Metabolism and Dermal P enetration

870.7485 Metabolism and

pharmacokinetics (rat) 41030132 (1988)

Acceptable Single oral dose 4.5 or 450 mg Repeated dose 4.5 or 450 mg for 14 days Clethodim is readily absorbed and eliminated (87

- 92%, urine; 9

- 17%, feces; < 1% expired air) after 7 days. Gastrointestinal absorption estimated at 89

- 96%. No evidence of bioconcentration. Extensively metabolized with < 1% eliminated as unchanged parent compound. Predominant metabolite is clethodim sulphoxide (48

- 68%) after 48 hours. 870.7600 Select 

### ® 2.0 EC

- 25.85% Clethodim Dermal penetration

(rat) 41030202 (1987)

Acceptable 0.05, 0.5, 5.0 mg/rat Based on the results of this study, the dermal absorption value for S elect 

### ® 2EC after 10

- hours of exposure, the typical worker exposure time, was 28.4%.

Neurotoxicity B attery

870.6200a Acute neurotoxicity

rats HanRcc:WIST (SPF) rats 48141801 (2006)

Unacceptable/non

guideline (Upgradable) 0, 10, 100, 1000 mg/kg (gavage) NOAEL = 100 mg/kg LOAEL = 1000 mg/kg based on clinical signs (decreased spontaneous activity, ruffled f ur, head tilt, hunched posture)

.

Acute neurotoxicity

rats Crl:CD(SD) rats 48788502 (2012)

Acceptable/non

- guideline 0, 10, 100, 1000 mg/kg (gavage) When the data from 2006 study (MRID 48141801) considered together with this study, NOAEL = 100 mg/kg LOAEL =1000 mg/kg based on combined clinical observations (decreased spontaneous activity, ruffled fur, head tilt, hunched posture).

870.6200b Subchronic

neurotoxicity

- rats 48788503 (2012)

Acceptable/non

- guideline 0, 500, 1500, or 5000 ppm M: 0, 31, 94, and 331 mg/kg/day, F: 0, 38, 115, and 380 mg/kg/day

48788501 (2012) dose range finding neurotoxicity study NOAEL = 94/115 mg/kg/day, M/F LOAEL = 331/380 mg/kg/day, M/F based on decreases in body weight, body weight gain, and food consumption.

Neurotoxicity was not observed in this study.

Immunotoxicity Studies

870.7800 Immunotoxicity

study in B6C3F1 mice 48788505 (2012)

Acceptable/guideline 0, 400, 2000, and 4000
ppm 0, 136, 603, 1312, and 0 mg/kg body weight/day 48788505 (2012) Range

finding study C lethodim did not produce immunotoxicity. NOAEL = 1312 mg/kg/day (HDT)

C lethodim M etabolites Studies

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Page 34 of 38 Table A.2.2. Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results

870.3100 Imine Sulfone 5

- Week oral

toxicity (rat) 41030104 (1988)

Acceptable/non

- guideline 0, 80.8, 871, 7820 ppm (nominal doses) Equivalent to 0, 6.7/7.8, 70.9/83.7, 604.0/723.0 mg/kg/day (M/F) Systemic Toxicity NOAEL = 70.9/83.7 mg/kg/day (M/F) Systemic Toxicity LOAEL = 604/723 mg/kg/day (M/F) based on increased serum cholesterol and increased liver weights.

870.3100 Clethodim High Purity w/process neutrals 5

- Week oral

toxicity (rat) 41030108 (1987)

Acceptable/ Nonguideline 0, 1200 (process neutrals), 6800 (high purity clethodim) ppm 4.9/5.8, 148/175 mg/kg/day (M/F) This study was not to establish a NOAEL or LOAEL. The high purity clethodim produced lower body weight gain, mild anemia and mild liver hypertrophy at 148/175 mg/kg/day (M/F).

870.3700a 5

- Hydroxy sulfone Prenatal

developmental in (rat) 41030118 (1988)

Acceptable/Nonguideline 0, 10, 100, 700 mg/kg/day Maternal Systemic Toxicity NOAEL ≥ 700 mg/kg/day Maternal Systemic Toxicity LOAEL > 700 mg/kg/day Developmental Toxicity NOAEL ≥ 700 mg/kg/day Developmental Toxicity LOAEL > 700 mg/kg/day

870.3700a Imine Sulfone Prenatal

developmental in (rat) 41030117 (1988)

Acceptable/non

- guideline 0, 10, 100, 700 mg/kg/day Maternal Systemic Toxicity NOAEL = 10 mg/ kg/day Maternal Systemic Toxicity LOAEL = 100 mg/kg/day based on reduced body weight gains and food consumption. Developmental Toxicity NOAEL = 100 mg/kg/day Developmental Toxicity LOAEL = 700 mg/kg/day based on reduced fetal body weights, reduced sternal ossification, and an increased incidence of a cervical rib. 870.5100 5

- Hydroxy

clethodim sulfone Gene Mutation 41030126 (1987) Acceptable Negative. There was no evidence of significant induced mutant colonies over background in strains TA98, TA100, TA1 535 and TA1537 and WP2 uvrA with and without S9 activation.

870.5100 Imine

sulfone Gene Mutation 41030127 (1988) Acceptable Negative. There was no evidence of significant induced mutant colonies over background in strains TA98, TA100, TA1535 and TA1537 and WP2 uvrA with and without S9 activation.

870.5375 Imine

sulfone CHO Assay 41030130 (1988) Acceptable Negative. There w as no evidence of a dose

related increase in structural chromosomal aberrations over background in the presence or absence of metabolic activation at any concentration tested up to the limit of solubility.

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Page 35 of 38 A ppendix B. Summary of Field Trial Data

Table B.1 . Summary of Residues from Apple Trials with Clethodim

. Crop Matrix Total Application

Rate (lb a i /A) PHI

(days) Analyte 1 n 2 Residues (ppm clethodim equivalents ) Min. 3 Max. 3 LAFT 4 HAFT 4 Median 4 Mean 4 SD 4

Apple 0.491

- 0.516 12

- 15 DME 10 < 0.095 <0.095 <0.095 <0.095 0.095 0.095 NA
DME

- OH <0.088 <0.088 <0.088 <0.088 0.088 0.088 NA Combined 5 <0.183 <0.183 <0.183 <0.183 0.183 0.183 NA
Pear 0.488

- 0.527 13

- 16 DME 6 <0.095 <0.095 <0.095 <0.095 0.095 0.095 NA
DME

- OH <0.088 <0.088 < 0.088 <0.088 0.088 0.088 NA Combined 5 <0.183 <0.183 <0.183 <0.183 0.183 0.183 NA
Plum fruit 0.490

- 0.512 12

- 14 DME 5 <0.095 <0.095 <0.095 <0.095 0.095 0.095 NA
DME

- OH <0.088 <0.088 <0.088 <0.088 0.088 0.088 NA Combined 5 <0.183 <0.183 <0.183 <0.183 0.183 0.183 NA Cherry fruit 0.496

- 0.530 13

- 16 DME 5 <0.095 <0.095 <0.095 <0.095 0.095 0.095 NA
DME

- OH <0.088 <0.088 <0.088 <0.088 0.088 0.088 NA Combined 5 <0.183 <0.183 <0.183 <0.183 0.183 0.183 NA

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Page 36 of 38 A ppendix C. International Residue Limits

Table C.1. Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition: 

### US Canada Mexico 2 

### Codex 2

40 CFR 180.458
(a ) General. Compliance with the tolerance levels specified in this paragraph is to be determined by measuring only the sum of clethodim,2

- [(1E)

- 1

- [[[(2E)

- 3

- chloro

- 2

- propenyl]oxy]imino]propyl]

- 5

- [2

- (ethylthio)propyl]

- 3

- hydroxy

- 2

- cyclohexen

- 1

- one, and its met abolites containing the 5

- (2

- ethylthiopropyl)cyclohexene

- 3

- one and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulphoxides and sulphones, calculated as the stoichiometric equivalent of clethodim 2

- [1

- [[[(2E)

- 3

- chloro

- 2

- propen

- 1

- yl]oxy]imino]propyl ]

- 5

- [2

- (ethylthio)propyl]

- 3

- hydroxy

- 2

- cyclohexen

- 1

- one, including metabolites containing the 2

- cyclohex

- 1

- enone moiety Sum of clethodim and its metabolites containing 5

- (2

- ethylthiopropyl)cyclohe

xene

- 3

- o ne and 5

- (2

- ethylthiopropyl)

- 5

- hydroxycyclohexene

- 3

- one moieties and their sulphoxides and sulphones, expressed as clethodim.



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 

### Codex 3 Onion, bulb, subgroup 3

- 07A 0.5 0 0.2 onions 0.5 onion bulb, garlic Vegetable, fruiting, g roup 8

- 10 1.0 1 tomato Fruit, pome, group 11

- 10 0.20 Fruit, stone, group 12

- 12 0.20 Berry, low growing, subgroup 13

- 07G

, except cranberry 3.0

Rapeseed subgroup 20A , except flax seed 0.50 0.05 rapeseed, mustard seed (oil seed type) 0.4 mustard seed (condiment type) 0.3 flaxseeds 0.5 rape seed 0.5 (*) cotton seed oil (crude and edible)

Sunflower subgroup 20B 5.0 0.2 0.5 sunflower see d 0.1 (*) sunflower seed oil crude Cottonseed subgroup 20C 1.0 0.5 cotton seed 0.5 (*) cotton seed oil (crude and edible) Stevia , dried leaves 12 Completed by: M. Negussie; 10/07/15 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 quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commod ity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

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Page 37 of 38 Appendix D. Physical/Chemical Properties

Table D .1 Physico

- Chemical Properties
Parameter Value Reference Molecular weight 359.91 g/mol MRID 46124103 pH 4.1 1,2 MRID 46124103 Water solubility (20°C) 0.54 g/100 mL (pH 7.0) MRID 48881405 Solvent solubility (20°C to 25°C) > 90 g/100 mL in most solvents MRID 46124103
Vapor pressure (25°C) <1 × 10

- 2 mPa at 20°C 1 × 10

- 7 mm Hg at 20°C MRID 48881405
Dissociation constant, pKa 4.62 MRID 48881405 Octanol/water partition coefficient, log K OW (25°C) 4.51 (21°C) MRID 48881405

Aerobic soil half

- life (20°C) 1.2 days MRID 41376801 2.5 days MRID 40974522 Photolysis half

- life in soil (13

- 23  C) 7 days MRID 41030135

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Page 38 of 38 Appendix E. Review of Human Research

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 the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); and the Agricultural Handler Exposu re Task Force (AHETF) database are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies that 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 at http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.