CLETHODIM Human Health Risk Assessment DP No. D425763 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: Apri 1 18, 2016 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Clethodim. Human Health Aggregate Risk Assessment for the Proposed New Uses 

on Ste via, Pome Fruit Group 11-10, Stone Fruit Group 12-12, Bulb Onion 

Subgroup 3-07 A, Low Growing Berry Subgroup l 3-07G, (except Cranberry); 

Rapeseed Subgroup 20A (except Flax Seed), Sunflower Subgroup 208, Cottonseed 

Subgroup 20C, and Fruiting Vegetable Group 8-l 0. 

PC Code: 121011 

Decision No.: 497978 

Petition No.: 4E8334 

Risk Assessment Type: Single 

Che in ical/ Aggregate Assessment 

DP Barcode: 0425763 

Registration Nos.: 59639-3, 59639- 132 

Regulatory Action: Section 3 

Case No.: 7226 

TXR No.: NA CAS No.: 99 129-21-2 

MRIO No.: NA 40 CFR: § 180.458 

FROM: Laura 

Meher

No

et Neg

llen

u

, 

ss

Biologist 

ie, Chemi

and 

st 

Ri

/'teA~ sk Assessok~~ 

r d ~ ~ 

Whang Phang, Senior ox co lo gist/vv~ w~ 

Risk Assessment Branch 3 (RAB3)/Health Effects Division (7509P) 

THROUGH: Christine Olinger, Branch Chief .# ,# vj' C" 

RAB3/HED (7509P) {;/° t ~ 

TO: Sidney Jackson, Biologist; Barbara Madden, Team Leader, RM #5 

Minor Use and Emergency Response Branch 

Heather Garvie, Lisa Pahel, PM Team #24 

Registration Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (BED) conduct a risk 

assessment for the active ingredient (ai) clethodim. A summary of the findings and an 

assessment of human health risks resulting from the proposed and registered uses of clethodim 

are provided in this document. The toxicology and hazard database review was conducted by 

Whang Phang; the drinking water assessment was conducted by Greg Orrick; the dietary and 

residue chemistry reviev,1s were conducted by Meheret Negussie; and the occupational/residential 

exposure assessment and the aggregate human health risk assessment were conducted by Laura 

Nollen. 

Page 1 of 38 
CLETHODIM Human Health Risk Assessment DP No. 0425763 

1.0 Executive Sun1mary ................................................................................................ .. ......... 4 

2.0 HED Recommendations .... .... .... .... .................. .... .... ......... .............................................. ... 6 

2.1 Data Deficiencies .... .... ........ .......................................................................... ... ... .... ........ 6 

2.2 Tolerance Considerations ........................... ..... ........................... ................. ... ... .... ... ... .. 7 

2.2.1 E nforcement Analytical Method ............ .... ......... .... ....... .............. ............................. 7 

2.2.2 Recommended Tolerances .......................... ............................................................... 7 

2.2.3 Revisions to Petitioned-For Tolerances .................................................................... 8 

2.2.4 International Harmonization .................................. ................................................... 9 

2.3 Label Recommendations ........................ ......................... ............ ................................. I 0 

2.3. l Recommendations from Residue Reviews .............................................................. I 0 

2.3.2 Recommendations from Occupational Assessment.. ............................................. I 0 

2.3.3 Recommendations from Residential Assessment.. ... ................................ ... ...... ..... I I 

3.0 Introduction .. ....... .... .... .... .... .................................. ..... .... ........ ... .... ... ........... ............. ... ... .. 11 

3.1 Chemical Identity .................................................. .... .................................... ... ... ... ...... 12 

3.2 Physical/Chemical Characteristics ..................... ........................................ ................ 12 

3.3 Pesticide Use Pattern .................................................................................................... 12 

3.4 Anticipated Exposure Pathways ................................................................................. 13 

3.5 Consideration of Environmental Justice .................................................................... 14 

4.0 Hazard Characterization and Dose-Response Assessment ........ .................................. 14 

4.1 Summary of Toxicological Effects ................................................................ .............. 14 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) .................... ........... 15 

4.2.J Completeness of the Toxicology Database ....... ........................................ ...... .... ... .. 16 

4.2.2 Evidence of Ncurotoxicity ............................................................................... ... ... ... 16 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.. ...... 16 

4.2.4 . Residual Uncertainty in the Exposure Database ................................................... 16 

4.3 Toxicity Endpoint and Point of Departure (POD) Selections ........................... ....... 16 

4.3.1 Recommendation for Combining Routes of Exposure for Aggregate Risk 

Assessment .......................... ..... .... ................................... ........ ................................................. 1 7 

4.3.2 Cancer Classification and Increased Tumor Incidence Risk Assessment 

Recommendation ..................................................................................................................... 17 

5.0 Dietary Exposure and Risk Assessment ......... ..................... .... ....... .... ... ....... ... .......... ..... 18 

5.1 Residues of Concern Summary and Rationale ... .... .... .... ... ............... ... .......... ... ......... 18 

5.2 Food R.esidue Profile ......... .................................................................................. ... ...... 19 

5.3 Water Residue Profile .................................................................................................. 20 

5.4 Dietary Risk Assessment .............................................................................................. 20 

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 20 

5.4.2 Acute Dietary Risk Assessment ....................... .... .... .... ................................... ......... 21 

5.4.3 Chronic Dieta ry Risk Assessment .................................. .......... ............... ................ 21 

5.4.4 Cancer Dietary Risk Assessment .. ............. ..... ............ .... .... ... ....... ....... .......... ... ....... 21 

5.4.5 Sun1mary Table .................... .... .............. .............................................. .... ................. 21 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 22 

6.1 Residential Risk Estimates for Use in Aggregate Assessment.. ................................ 22 

6.2 Residential Bystander Post-application Inhalation Exposure ............................. .... 23 

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

7.0 Aggregate Exposure/Risk Characterization .................... ......................................... ..... 24 

7.1 Acute Aggregate Risk ................... ................................................................................ 24 

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CLETHODIM Human Health Risk Assessment DP No. D425763

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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

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1.0 Executive Summary

Clethodim, 2-[(1E)-1-[[[(2E)-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. The Interregional Research Project 

Number 4 (IR-4) has submitted pesticide petition (PP#) 4E8334, requesting the establishment of 

permanent tolerances for residues of clethodim in or on Stevia, Pome fruit group 11-10, Stone 

fruit group 12-12, Bulb onion subgroup 3-07A, Low growing berry subgroup 13-07G (except 

cranberry), Rapeseed subgroup 20A (except flax), Sunflower subgroup 20B, Cottonseed 

subgroup 20C, and Fruiting 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, Valent 

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) EUPs containing 

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-resistant 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 exposure sources. Based on all of the proposed application rates and label 

information, dietary exposures are expected for acute and chronic durations; residential handler 

and post-application dermal and inhalation exposures are expected only for short-term durations; 

and occupational 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 weights, clinical chemistry changes, and centrilobular 

hepatic hypertrophy. Most of the liver effects that occurred at or below 100 milligrams/kilogram 

body weight (mg/kg bw) were considered adaptive effects. Decreased body weight was also a 

common finding across 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

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Developmental effects were not present in rabbits, and the toxicity data did not show an 

increased susceptibility 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 reproductive 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 carcinogenic 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 μg/L and 1,150 μg/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 reassessed using HED’s 2012 Residential 

SOPs1. 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-application 

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 potential for short-term aggregate exposure to clethodim for adults via the dietary 

(background exposure) 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 expected 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 assessments were not conducted. Because the 

 

1 Available: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-proceduresresidential-pesticide
CLETHODIM Human Health Risk Assessment DP No. D425763

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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 proposed 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-/intermediate-term inhalation risks are not of 

concern at baseline mitigation without personal protective equipment (PPE). The 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 Low-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 human 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 pursuant 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 on their use, can be found at the Agency website2. 

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 need to be fulfilled for the requested actions. However, an analytical 

reference standard for clethodim and clethodim S-methyl sulfoxide must be submitted (email 

communication with Teresa Cole, ACB, 03/24/2015). The registrant is required to submit a 

reasonable amount of the analytical reference standards. The reference standards 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

National 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

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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

IR-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/on 

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. These 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 FDA 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-26D-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-26D-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)propyl]-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 equivalent of 
CLETHODIM Human Health Risk Assessment DP No. D425763

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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 Table 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 subgroup 3-07A 0.2 0.50 Onion, bulb, subgroup 3-

07A. Increased tolerance to 

harmonize with Codex.

Vegetable, fruiting group 08-10 1.0 1.0 Vegetable, fruiting, group 

8-10

Fruit, pome group 11-10 0.2 0.20 Fruit, pome, group 11-10

Fruit, stone group 12-12 0.2 0.20 Fruit, stone, group 12-12

Berry, low growing, subgroup 13-

07G, except cranberry

3.0 3.0

Rapeseed subgroup 20A, except 

flax

0.5 0.50 Rapeseed subgroup 20A,

except flax seed

Sunflower subgroup 20B 5.0 5.0

Cottonseed subgroup 20C 1.0 1.0 Cottonseed 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 Vegetable, 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 Onion, bulb, subgroup 3-07A 

at 0.50 ppm 

Vegetable, fruiting 

group 8

1.0 Revoke Covered by Vegetable, 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 subgroup 20A, 

Mustard, seed 0.50 except flax seed at 0.50 ppm

Sesame, seed 0.35

Safflower, seed 5.0 Revoke Establish as Sunflower subgroup 20B at 

Sunflower, seed 5.0 5.0 ppm

Cotton, undelinted 

seed

1.0 Revoke Establish as Cottonseed subgroup 20C at 

1.0 ppm

2.2.3 Revisions to Petitioned-For Tolerances
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As summarized below, some of the proposed 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 limits (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 Vegetable, fruiting group 08-10; Fruit,

pome group 11-10; Fruit, stone group 12-12; and Rapeseed 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), 

rapeseed (0.5 ppm), sunflower seed (0.5 ppm), and cotton seed (0.5 ppm).

The U.S. tolerance for Rapeseed 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) MRLs, respectively. 

The U.S. and Codex MRLs are not harmonized for Sunflower subgroup 20B or Cottonseed 

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 Sunflower subgroup 20B (5.0 ppm) and 

Cottonseed subgroup 20C (1.0 ppm) could not be harmonized with the Codex sunflower seed 

and cotton seed MRLs at 0.5 ppm, since the MRL values are lower than the recommended US 

tolerances. These 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 (0.50 ppm) cannot be harmonized with the 

Canadian MRL established on onions (0.2 ppm), as the U.S. is establishing the Subgroup 3-07A 

tolerance to harmonize with Codex at a higher tolerance level.
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The value for the U.S. tolerance on Vegetable, fruiting, group 8-10 (1 ppm) is harmonized with 

the Codex tomato (1 ppm) MRL. However, the Codex MRL was established on tomato only and 

does not include the other representative commodities of Crop group 8-10. 

The U.S. tolerance on Rapeseed subgroup 20A (0.50 ppm) could not be harmonized with the 

Canadian MRLs on rapeseed (0.05 ppm) or mustard seed (0.4 ppm), since the Canadian MRLs 

are established on individual crops. In addition, the Canadian MRL value is lower for rapeseed 

(representative commodity).

The U.S. tolerance on Sunflower subgroup 20B (5.0 ppm) could not be harmonized with the 

Canadian crop subgroup MRL, since the MRL value is lower (0.2 ppm) than 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 proposed 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) Subgroup 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 Recommendations 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 
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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 Sunflower 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 the 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 should 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 from Residential Assessment

Some clethodim products are intended 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 

specific 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 are intended to be marketed toward and 

applied by consumers/homeowners on residential ornamental plant beds, trees, or ground covers, 

HED recommends that label requirements for clothing and/or PPE be reevaluated or separate 

consumer-specific labels removing requirements for specific clothing or PPE be developed.

3.0 Introduction

Clethodim is a selective post-emergence cyclohexanedione 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 the roots as well as other growing plant parts. In plants, 

clethodim inhibits acetyl-CoA 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 group 12-12, Bulb onion 

subgroup 3-07A, Low growing berry subgroup 13-07G (except cranberry), Rapeseed subgroup 

20A (except flax seed), Sunflower subgroup 20B, Cottonseed subgroup 20C, and Fruiting 

vegetable group 8-10. The registrant, Valent U.S.A. Corporation, owns the EUPs associated with 

this action.
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3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature

Chemical Structure

Empirical Formula C17H26ClNO3S

Common Name Clethodim

Company experimental name RE45601

IUPAC name (5RS)-2-{(E)-1-[(2E)-3-chloroallyloxyimino]propyl}-5-[(2RS)-2-

(ethylthio)propyl]-3-hydroxycyclohex-2-en-1-one

CAS Name 2-[(1E)-1-[[[(2E)-3-chloro-2-propenyl]oxy]imino]propyl]-5-[2-

(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one

CAS Registry Number 99129-21-2

Chemical Class cyclohexenone

Known Impurities of Concern None

3.2 Physical/Chemical Characteristics

The physicochemical 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 (Kow) of 4.51 (at 20°C) 

which indicates moderate fat solubility; however, studies show minimal potential for 

bioaccumulation. At 20°C, the Henry’s Law constant was calculated to be <2×10-9atm·m3/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 Use Pattern

Table 3.3. Summary 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 NS2 0.5 45

For repeat applications 

make on a minimum of a 

14 day interval.

Pome fruit group 11-10 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.

O

OH

N

CH3

O Cl

S

CH3

H3C
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Table 3.3. Summary 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 not 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 representative 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 association 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 group 12-12, Bulb onion subgroup 

3-07A, Low growing berry subgroup 13-07G (except cranberry), Rapeseed subgroup 20A 

(except flax), Sunflower subgroup 20B, Cottonseed 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

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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 exposure 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 assessment for registration review 

of clethodim, dated 01/30/2014 (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, particularly 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/environmentaljustice/resources/policy/exec_order_12898.pdf). As a part of 

every pesticide risk assessment, OPP considers a large variety of consumer subgroups according 

to well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on 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 registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and 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 exposures 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 last risk assessment. This assessment includes 

summaries of prior assessments (N. Tsaur, DP411899, 01/30/2014)

4.1 Summary of Toxicological Effects
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In general, the clethodim toxicity database shows relatively low toxicity. With repeated dosing 

by the oral or 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 common finding 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 present 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 

offspring 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. Clethodim 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 showing the highest concentration of clethodim 

equivalents. There was no difference in the concentration of radiocarbon in the tissues between 

the repeated 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) 

hydroxylated 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 shown 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 sulfoxide (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 III) and mild skin irritation (Category IV), but it is not a dermal sensitizer.

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

For all assessment 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 
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is no evidence of neurotoxicity; and (4) there are no residual uncertainties in the exposure 

database. The details for these determinations are presented in the following sections:

4.2.1 Completeness of 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 during the first 

three days after dosing. Subsequently, treatment-related clinical signs were not present, and there 

were no histopathological 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 Evidence of Sensitivity/Susceptibility in the Developing or 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 

reproductive effects were found in the 2-generation reproduction study in rats. Therefore, there 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 reproduction study conducted for 

clethodim.

4.2.4 Residual Uncertainty in the Exposure Database

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 (PCT)

assumptions and conservative drinking 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 estimates are based on conservative assumptions that are not 

likely to result in underestimated risk.

4.3 Toxicity Endpoint and Point of Departure (POD) Selections

Since the last published risk assessment for clethodim, there have been no changes to the doseresponse 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.
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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 routespecific dermal toxicity study, and no concerns for developmental or reproductive effects were 

seen elsewhere in the database.

4.3.1 Recommendation for Combining Routes of Exposure for Aggregate Risk 

Assessment

No dermal hazard has been identified for clethodim. Oral and inhalation routes can be combined 

for short-term risk assessments, due to the selection of a common toxicological 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 risk assessments 

do not need to be conducted. 

Table 4.3. Summary of Toxicological Doses and Endpoints for Clethodim for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All 

Populations)

NOAEL = 

100 

mg/kg/day

UFA = 10X

UFH = 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 observations included 

decreased spontaneous activity, ruffled fur, 

head tilt, and hunched posture

Chronic 

Dietary

(All 

Populations)

NOAEL = 

30 

mg/kg/day

UFA = 10X

UFH = 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 ShortTerm

(1-30 days)

NOAEL = 

75

mg/kg/day

UFA = 10X

UFH = 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.
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Table 4.3. Summary of Toxicological Doses and Endpoints for Clethodim for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal

Short-Term

(1 to 30 days) 

and 

IntermediateTerm

(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 

IntermediateTerm

(1-6 months)

NOAEL = 

75 

mg/kg/day

UFA = 10X

UFH = 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.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 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 major metabolic pathways for clethodim (C) in tested 

crops are initial sulfoxidation to clethodim sulfoxide (CSO) followed by further oxidation to 

clethodim sulfone (CSO2). The elimination of the chloroallyloxy side chain yields the imine 

sulfoxide (ISO) and sulfone (ISO2), and the hydroxylation of these compounds forms the 5-OH 

sulfoxide (5OH-SO) and sulfone (5OH-SO2). Clethodim sulfoxide and clethodim sulfone 

conjugates were also detected as major or minor metabolites, depending on plant species and 

sub-fractions. 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 chlorine atom and 

incorporating the three carbon moieties into natural plant components (with some being evolved 

as 14CO2). 

A confined rotational crop study of [ring-4,6-

14C]-clethodim, conducted with carrots, lettuce, and 

wheat, was previously reviewed (MRID 41030211; EFGWB Science Chapter for Clethodim, E. 
CLETHODIM Human Health Risk Assessment DP No. D425763

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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 

limitations 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-

14C]-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-ethylthiopropyl)-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

Adequate residue data are available to support the proposed tolerances for the herbicide 

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), were 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. 
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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, 

D425767, 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 “water, 

indirect, all sources.”

Based 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 structurally 

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, respectively) 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 Model 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 an unrefined chronic dietary (food and drinking water) risk assessment for 

clethodim using exposure and risk estimates obtained from the Dietary Exposure Evaluation 

Model using the Food Commodity Intake Database (DEEM-FCID; version 3.16). The model 

uses food consumption data from the Department of Agriculture’s (USDA’s) 2003-2008 
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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 version 7.81 except for tolerances that were 

established 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 (aPAD) for 

the general U.S. population and 29% of the aPAD 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, and 

clethodim is classified as “not likely to be carcinogenic to humans;” therefore, cancer risk was 

not assessed

5.4.5 Summary Table

Table 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
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Table 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 updates to HED’s 2012 

Residential SOPs3along 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 residential 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 products are intended for use in landscaped areas, ornamental 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., ornamental 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 estimate 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 gardens, 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 Residential 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.epa.gov/pesticides/science/residential-exposure-sop.html
CLETHODIM Human Health Risk Assessment DP No. D425763

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 The recommended residential exposure for use in the adult aggregate assessment 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 residential 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 MOE2

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 Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-

0037). The Agency has evaluated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency 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 rates (0.0455 to 0.25 lb 

ai/A/application). A quantitative spray drift analysis also indicated no risks of concern following 

spray drift of clethodim 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 estimates 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 were assessed. The highest exposure resulted from drift following clethodim 
CLETHODIM Human Health Risk Assessment DP No. D425763

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applications using aerial or groundboom equipment for children 1 to <2 years old. The hand-tomouth MOEs modeled at the edge of the field ranged from 53,000 and 110,000 for aerial and 

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 water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

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 expected for the residential exposure pathway. Therefore, the acute 

aggregate risk would be equivalent to the acute dietary exposure estimates. 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 exposure 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 common. 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 Term Aggregate Risk Calculations

Population

Short- or Intermediate-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adults6 75 100 0.75 0.034796 0.00001186 0.03480786 2,200

1 LOC = 100, 10X UFA, 10X UFH, 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
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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 drinking 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 

dietary (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 mechanism 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 mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://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 group 12-12, Bulb onion subgroup 3-07A, Low growing berry 

subgroup 13-07G (except cranberry), Rapeseed subgroup 20A (except flax seed), Sunflower 

subgroup 20B, Cottonseed subgroup 20C, and Fruiting vegetable group 8-10. Short- and 

intermediate-term occupational exposures to clethodim are expected, based 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 be 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 application scenarios for orchards/vineyards were not previously 

assessed. Therefore, this document addresses the occupational handler and post-application 

exposure and risks resulting from broadcast applications of clethodim using groundboom 

equipment in orchards or vineyards only. The only quantitative exposure/risk assessment 

scenarios that were assessed for occupational handlers are as follows: 
CLETHODIM Human Health Risk Assessment DP No. D425763

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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 

shirts and long pants, chemical-resistant gloves such as barrier laminate or viton ≥ 14 mils, shoes 

plus socks, and protective eyewear.

The results of the occupational handler exposure 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 short-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. Occupational Handler Non-Cancer Exposure and Risk Estimates for Clethodim.

Exposure 

Scenario Crop or Target2 Level of Concern

Inhalation 

Unit 

Exposure 

(μg/lb ai) 3

Maximum 

Application 

Rate5

(lb ai/A)

Area Treated 

or Amount 

Handled 

Daily (A)6

Inhalation

Level of PPE4 Dose 

(mg/kg/day)7 MOE8

Mixer/Loader

Groundboom 

Broadcast 

(EC1)

Orchard/vineyard 100

0.219

0.125 40 0.0000138 5,400,000 Baseline

Applicator

Groundboom 

Broadcast 

(Spray)

Orchard/vineyard 100

0.34

0.125 40 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 Science Advisory Council Policy #9.1.

7 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × 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 referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.
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9.2.1 Dermal Post-application Risk

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

post-application activities on agricultural crops. However, no dermal toxicity endpoints or PODs 

were selected for risk assessment. Therefore, a quantitative dermal post-application 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 not needed at this time.

Restricted Entry Interval

The REI specified on the proposed EUPs is based on the 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 Statements 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

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-0037). The Agency 

has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review for clethodim, based on the Agency's current practices, a quantitative post-application 

inhalation exposure assessment was not performed, primarily because of the low acute inhalation 

toxicity (Toxicity Category IV), low vapor pressure (<1x10-7 mm Hg), and the low use rate 

(0.125 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

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L. Nollen, 12/17/2015, DP425763, “Clethodim. Occupational and Residential Exposure 

Assessment for Proposed Uses on Stevia, Pome Fruit Group 11-10, Stone Fruit Group 12-12, 

Bulb Onion Subgroup 3-07A, Low Growing Berry Subgroup 13-07G, (except Cranberry); 

Rapeseed Subgroup 20A (except Flax), Sunflower Subgroup 20B, Cottonseed Subgroup 

20C, and Fruiting Vegetable Group 8-10.”

M. Negussie, 01/12/2016, DP431225, Clethodim: Tolerance Petition for New Uses on Stevia; 

Pome Fruit Crop Group 11-10; Stone Fruit Crop Group 12-12; and Crop Group/Subgroup 

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. Negussie, 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 

Onion, 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, Cotton Seed Subgroup 20C, 

and Fruiting Vegetable Group 8-10.”

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

Registration Review.”
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Appendix 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 Clethodim

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

waivedb

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.
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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)

LD50 =

males 1.63 g/kg 

females 1.36 g/kg

III

870.1200 Acute dermal [rabbit] 40974510

(1986) LD50 > 5.0 g/kg IV

870.1300 Acute inhalation [rat] 40974512

(1986) LC50 > 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 [guinea pig] 40974518

(1986)

not 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 liver 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 (Highest dose tested, 

HDT)

870.3100 90-Day oral toxicity 

(rat) with 6 week 

recovery groups

41030107 (1986)

Acceptable/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).
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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 

correlates 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)

Skin 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].

Dermal irritation was seen in all treatment 

groups.

870.3465 90-Day inhalation 

study 

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

TXR 0056491)

Developmental 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 anogenital staining).

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)

Acceptable/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 (increased 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) 
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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 Studies

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 treatmentrelated effects on survival, decreased red cell 

mass (decreased erythrocyte counts, 

hemoglobin, and hematocrit values), increased 

liver weights, 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 Battery

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 treatmentrelated 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 limits 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 doserelated 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)

Negative. There is no evidence that clethodim 

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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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 Penetration 

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 Select® 2EC after 10-

hours of exposure, the typical worker exposure 

time, was 28.4%.

Neurotoxicity Battery

870.6200a

Acute neurotoxicityrats

HanRcc:WIST

(SPF) rats

48141801 (2006)

Unacceptable/nonguideline (Upgradable)

0, 10, 100, 1000 mg/kg 

(gavage) 

NOAEL = 100 mg/kg

LOAEL = 1000 mg/kg based on clinical signs 

(decreased spontaneous activity, ruffled fur, 

head tilt, hunched posture).

Acute neurotoxicityrats

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) Rangefinding study

Clethodim did not produce immunotoxicity. 

NOAEL = 1312 mg/kg/day (HDT)

Clethodim Metabolites Studies
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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-Hydroxyclethodim 

sulfone

Gene Mutation 41030126 (1987)

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. 

870.5100 

Iminesulfone

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

IminesulfoneCHO Assay 41030130 (1988)

Acceptable

Negative. There was no evidence of a doserelated 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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Appendix B. Summary of Field Trial Data

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

Crop 

Matrix

Total Application 

Rate

(lb ai/A)

PHI 

(days)

Analyte1 n

2 Residues (ppm clethodim equivalents)

Min.3 Max.3 LAFT4 HAFT4 Median4 Mean4 SD4

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

Combined5 <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

Combined5 <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

Combined5 <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

Combined5 <0.183 <0.183 <0.183 <0.183 0.183 0.183 NA
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Appendix C. International Residue Limits

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

Residue Definition:

US Canada Mexico2 Codex2

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 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 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-one and 5-(2-

ethylthiopropyl)-5-

hydroxycyclohexene-3-

one moieties and their 

sulphoxides and 

sulphones, expressed as 

clethodim.

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Onion, bulb, subgroup 3-07A 0.50 0.2 onions 0.5 onion bulb, garlic

Vegetable, fruiting, group 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 seed

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 commodity, 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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Appendix D. Physical/Chemical Properties

Table D.1 Physico-Chemical Properties

Parameter Value Reference

Molecular weight 359.91 g/mol MRID 46124103

pH 4.11,2 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 KOW

(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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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 

Exposure 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.